Olfactics and Olfactory Theranostics

Research Over Despair

2026-01-05T13:42:00.000-08:00

I am always glad to receive letters from people who, despite facing real difficulties, are motivated to understand their condition and actively look for solutions. This letter was one of those.

It came from a young person who had lived with PATM (People Allergic to Me) for just over a year. In that short time, the condition had disrupted education, lab work, friendships, and mental health. Like many others with PATM, this individual had been told - explicitly or implicitly - that what they were experiencing might not be real.

What struck me most was not the suffering (which, sadly, is familiar), but the decision that followed: instead of giving up, they chose to learn, to research, and to ask whether science might eventually provide answers - not only for themselves, but for others.

Below is a modified, bulletized and anonymized version of my response to their questions, shared here because many patients ask the same things.

Why is PATM still an undiagnosed condition?

PATM is often described as “undiagnosed,” but a more accurate term would be not formally recognized.

For a condition to become a recognized clinical entity, several things usually need to be in place:

a consistent case definition
reproducible, objective measurements
and a plausible pathophysiological mechanism that can be validated by multiple independent groups

At present, PATM does not yet meet all of these thresholds.

One major challenge is heterogeneity. The presentation varies widely from person to person, and triggers differ depending on environment, exposure, and individual biology. Another major obstacle is that current clinical workflows are poorly suited to capture intermittent, airborne chemical events. Many patients describe symptoms that occur in bursts—so a clinical visit may appear “normal,” even when the lived experience is not.

What would it take to achieve a formal medical diagnosis?

Large clinical trials can help, but they are rarely the starting point.

The real bottlenecks are:

reproducible measurement methods
defining subtypes rather than assuming a single mechanism
capturing the episodic (“bursty”) nature of emissions

A well-designed, multicenter observational study—with standardized sampling protocols and careful timing relative to symptoms—may be a more realistic bridge step than jumping directly to intervention trials.

An official diagnosis could be beneficial. It can legitimize patients’ experiences in clinical settings, redirect care away from reflexive psychologization and attract more serious research attention. But such a diagnosis has to be built on solid evidence to endure.

Is toluene the main irritation-causing substance?

It is unlikely that there is a single universal compound responsible for PATM.

Research on skin gas emission profiles is important because it demonstrates measurable chemical differences, but the broader picture likely involves multiple emitted mixtures and multiple subtypes. In some individuals, compounds such as toluene or related aromatics may contribute to irritation-like symptoms; in others, different chemical patterns may dominate.

Another key factor may be differences in detoxification or clearance. Some people appear more susceptible to everyday exposures—such as secondhand smoke, solvents, or indoor VOCs—not because exposure is higher, but because metabolism and elimination differ.

What can patients realistically try on their own?

I generally recommend starting with low-risk, high-information approaches:

Structured symptom and exposure logging

Tracking timing, diet, stress, environment (workplace, vehicles, indoor air), laundry and personal care products, and proximity to smoke or solvents can help identify repeatable patterns.

Basic medical rule-outs

Even when PATM is the primary concern, it is important to evaluate common contributors to odor or irritation-related conditions, such as reflux, sinus disease, metabolic or endocrine issues, liver and kidney function, medication effects, and dermatologic conditions.

Environmental controls

VOC-related problems are often exposure-amplified. Fragrance-free products, avoiding solvent-heavy cleaners, improving ventilation, and using HEPA plus activated carbon filtration can reduce background “noise” and make patterns easier to recognize.

I generally advise caution with high-risk or expensive interventions unless there is a clear rationale for a particular subtype.

What about fecal microbiota transplants (FMT)?

FMT is scientifically interesting but should be approached with caution. It is not a general solution for PATM and carries nontrivial risks. If considered at all, it should be under appropriate medical supervision and based on a specific, individualized hypothesis—not as a last-resort experiment.

Are microbiome or skin-gas profiling tests useful?

They can be, if used carefully.

Gut microbiome profiling may provide clues, but interpretation is still limited and should always be paired with symptom timelines, diet, and repeat measurements.
Skin or exhaled gas profiling is conceptually promising because it targets the suspected output directly. However, episodic emissions make timing critical, and passive sampling methods may miss short-lived events.

The usefulness depends less on the technology itself and more on study design.

Would wearable or portable gas sensors help?

In principle, yes. Continuous or frequent measurement could finally correlate chemical signatures with symptoms and environmental context.

In practice, true GC–MS–grade performance in a wearable format remains extremely challenging. Field measurements are complicated by changing ambient air, and episodic emissions require high time resolution and careful baseline correction. The idea is sound; the technology is still catching up.

Could funding agencies support this kind of work?

Possibly more so now than in the past.

Historically, conditions that primarily affect quality of life rather than mortality have struggled to gain funding. When I first applied for support nearly two decades ago, the problem was explicitly described as “not important enough.”

Today, there is broader recognition of the impact of stigma, mental health, and chronic quality-of-life impairment. Advances in exposomics, microbiome science, and wearable sensing technologies make it easier to frame this work as high-risk, high-reward, particularly if the focus is on measurement platforms, subtyping, and mechanism rather than a single compound.

Much of this may sound like a list of obstacles. But compared with even a decade ago, the path forward is clearer.

If PATM turns out not to be one condition but a family of related ones, that is not a failure of science—it is a more accurate description of biology. Progress will likely come not from searching for a single universal cause, but from building frameworks that can accommodate diversity, intermittency, and complexity.

And sometimes, progress begins with a patient who decides that understanding is better than silence.

Diets That Dial Down TMA (and TMAO): What Latest Studies Suggest

2025-10-19T12:35:00.000-07:00

This week's TL;DR: Diets that are high in fiber and lower in animal protein, plus Mediterranean-style eating, are emerging as the most food-first ways to reduce gut production of trimethylamine (TMA) and its oxidized form TMAO. Early evidence also points to targeted botanicals and postbiotics as promising add-ons - especially for people with heart or kidney concerns. If you live with MEBO/TMAU, the same general principles may apply.

What seems to help most

1) High-fiber, lower-protein patterns (especially for CKD).
A fiber-rich, modest-protein intake can rebalance gut microbes and lower circulating TMAO in chronic kidney disease. Think: loads of vegetables, legumes, whole grains, nuts/seeds—while keeping total protein moderate and favoring plant sources. (Udomkarnjananun et al., 2025)

2) Mediterranean diet (MED).
A short, 4-week MED intervention—vegetables, fruits, legumes, whole grains, olive oil, nuts; limited red/processed meat—significantly reduced blood TMAO, even in healthy adults. Men in the study also saw better lipids and anthropometrics. (Deniz & Baş, 2025)
Since fish contains pre-formed TMAO that can worsen odor in TMAU, adapt a fish-free Mediterranean pattern if you’re sensitive.

3) Botanicals with gut–heart effects (CHF).
In patients with chronic heart failure, the Chinese botanical formula Qili Qiangxin (QLQX) reduced BNP, TNF-α, IL-6, and TMAO, pointing to lower systemic inflammation and improved barrier function. Food pattern still matters, but this suggests a potential adjunct under medical guidance. (Zhu et al., 2025)

Qiliqiangxin consists of extracts from eleven traditional Chinese medicinal herbs including for example: Panax ginseng (ginseng), Astragalus mongholicus (Mongolian milkvetch), Salvia miltiorrhiza (red sage), Cinnamomum cassia (cinnamon twig), Aconitum carmichaelii (Chinese aconite root), Descurainia sophia (flixweed), Periploca sepium (Chinese silkvine root bark), Alisma plantago-aquatica subsp. orientale (Oriental waterplantain), Carthamus tinctorius (safflower), Polygonatum odoratum (Angular Solomon's seal), and Citrus reticulata (dried mandarin peel)

4) Postbiotics (preclinical but intriguing).
In a choline-boosted, high-fat mouse model of atherosclerosis, Weizmannia coagulans JA845 postbiotics (based on B. coagulans JA845) lowered TMAO, improved the microbiome profile, dampened JAK/STAT3 inflammation, and protected vessels. Human data are pending, but this supports the microbiome-modulation avenue alongside diet. (Ma et al., 2025)

Unlike probiotics (which are live microorganisms) and prebiotics (which are food/substrates that feed beneficial microbes), postbiotics are non-live microbial cells, microbial cell parts, or microbial metabolites (or a mix) that can have beneficial effects.

Example components might include dead/inactivated bacterial cells, cell wall fragments, microbial metabolites like short-chain fatty acids (SCFAs: butyrate, acetate, propionate), peptides and enzymes.

REFERENCES

Udomkarnjananun S, Chuaypen N, Metta K, Dissayabutra T, Sodsai P, Kittiskulnam P, Tangkijvanich P. Dietary composition modulate gut microbiota and related biomarkers in patients with chronic kidney disease. Sci Rep. 2025 Oct 16;15(1):36274. doi: 10.1038/s41598-025-20266-5. PMID: 41102296; PMCID: PMC12533112.

Zhu F, Hu R, Lv C, Wang J, Du X, Zeng X, Huang Y, Ma Y, Yang C, Guo F. Qili Qiangxin ameliorates chronic heart failure: a randomized clinical trial of biomarkers, inflammation, and cardiac outcomes. Front Pharmacol. 2025 Sep 30;16:1605944. doi: 10.3389/fphar.2025.1605944. PMID: 41098835; PMCID: PMC12518405.

Deniz MŞ, Baş M. Short-Term Mediterranean Dietary Intervention Reduces Plasma Trimethylamine-N-Oxide Levels in Healthy Individuals. Nutrients. 2025 Sep 30;17(19):3135. doi: 10.3390/nu17193135. PMID: 41097210; PMCID: PMC12525710. Ma L, Li N, Zhao Z, Zhao Y,

Yang G, Zhao L, Li S. Weizmannia coagulans JA845 Postbiotics Alleviate Atherosclerosis via TMAO-Related Gut Microbiota Regulation and JAK/STAT3 Pathway Inhibition. Nutrients. 2025 Sep 23;17(19):3027. doi: 10.3390/nu17193027. PMID: 41097105; PMCID: PMC12526339.

AI meets MEBO

2025-08-13T12:37:00.000-07:00

After a bit of a break since our first podcast back in March, we’re excited to return with a brand new episode for the MEBO and PATM community.

In this video, we’re exploring a big question: Can patients themselves use AI to help uncover potential causes, connections, and treatments for their symptoms?

The episode was generated by NotebookLM, based on our own research and the outputs of multiple large language models answering real questions from patients and researchers about these conditions. It’s a very good discussion overall - balanced, empathetic, and realistic about the challenges - but there are a few small hiccups.

For example, the video says that the paper "Cutaneous Bacteria in the Gut Microbiome as Biomarkers of Systemic Malodor and People Are Allergic to Me (PATM) Conditions" was published in Frontiers in Psychiatry in 2022. In fact, it appeared in JMIR Dermatology, a peer-reviewed journal, but one that isn’t indexed in PubMed - so it often doesn’t register in medical literature searches. Interestingly, when we asked half a dozen more LLMs about this paper, none knew much about it. Some even called it “groundbreaking” or “a beacon” without actually having the details, and a few hallucinated links that don’t exist.

PATM and MEBO are still often misclassified or linked to Olfactory Reference Syndrome, but there is growing recognition that underlying microbial dysbiosis or metabolic disorders may play a role.

Still, the bigger picture is encouraging: LLMs are improving, and that gives hope for people living with under-researched, heterogeneous, and often misunderstood conditions. While this podcast focuses a bit more on social and emotional support than on treatment options, that’s also an essential part of living with these conditions - and it makes this video worth watching.

Let’s dive in and see what AI can - and can’t - offer us right now.

A EURORDIS and NORD Member Organization

The Smell of Life

2025-04-16T17:43:00.000-07:00

Sulfur-rich smells are easy to recognize—think of the ocean at low tide, a bit of garlic, or even bad breath. While not always pleasant, they’re often tied to life processes. On Earth, compounds like dimethyl sulfide (DMS) and dimethyl disulfide (DMDS) are made by microbes, plants, and even our own bodies. For example, DMS is a byproduct of marine algae, and both DMS and DMDS are linked to the metabolism of sulfur-containing foods like garlic and onions.

Interestingly, these same compounds can also show up when organic matter breaks down. Over time, the mix of smells changes—starting with more sulfur notes like DMDS and shifting toward other compounds like ketones and acids. But in the early stages, it’s sulfur that dominates the scent, reinforcing that these molecules are deeply tied to life, not just what comes after it.

They even show up in everyday biology—DMS contributes to halitosis (bad breath), and sulfur compounds in urine can reveal what you’ve eaten recently, like garlic or leeks. And while they can be a nuisance in places like sewers due to their strong odor and reactivity, these volatile sulfur compounds are powerful chemical clues that life is (or was) at work.

Reported Sensory Thresholds for Sulfur Compounds

Compound	Structure	Sensory Description	Range (ppb)
hydrogen sulfide	H₂S	rotten egg, sewage-like	0.9 - 1.5
ethyl mercaptan	CH₃CH₂SH	burnt match, sulfidy, earthy	1.1 - 1.8
methanethiol, methyl mercaptan	CH₃SH	skunk, flatulence, rotten cabbage, burnt rubber	1.5
diethyl sulfide	CH₃CH₂SCH₂CH₃	rubbery	0.9 - 1.3
DMS, dimethyl sulfide	CH₃SCH₃	ocean, canned corn, cooked cabbage, asparagus	17- 25
diethyl disulfide	CH₃CH₂SSCH₂CH₃	garlic, burnt rubber	3.6 - 4.3
DDMS, dimethyl disulfide	CH₃SSCH₃	vegetables, cabbage, onion-like at high levels	9.8 - 10.2
carbon disulfide	CS₂	sweet, ethereal, slightly green, sulfidy	5

Imagine cracking open a clam at low tide or walking through a marsh at dusk. The faint, tangy smell of sulfur in the air? That’s dimethyl sulfide (DMS), a molecule born of life. It’s a scent tied to oceans, microbes, and biology itself.

Now picture that same signature—those familiar chemical traces—not wafting from Earth’s shoreline but drifting through the atmosphere of a distant world. That’s exactly what a team of astronomers, led by Nikku Madhusudhan at the University of Cambridge, believe they may have found.

Using the James Webb Space Telescope (JWST), they detected not only dimethyl sulfide (DMS) but also dimethyl disulfide (DMDS) in the atmosphere of exoplanet K2-18b orbiting a star 124 light-years away. On Earth, these molecules are exclusively produced by living organisms, especially marine phytoplankton and sulfur-reducing microbes.

Is this the first scent of alien life?

K2-18b has long intrigued scientists. Discovered in 2015 and confirmed to host water vapor in its atmosphere by 2019, it lies in the habitable zone of its star—a region where liquid water could exist. The planet is a sub-Neptune, about 8 times the mass of Earth, likely hosting a vast ocean beneath a hydrogen-rich sky.

When JWST's near-infrared instrument first picked up hints of DMS, the signal was tantalizing but faint. Now, using its mid-infrared camera, a much stronger signal has emerged—not just for DMS, but for DMDS, a closely related molecule. Both are complex sulfur-containing compounds known to be byproducts of living metabolic processes—especially those involving the breakdown of dimethylsulfoniopropionate (DMSP), an osmolyte made by marine algae.

On Earth, the sulfur cycle involves a complex web of microbial transformations, particularly in anoxic oceanic zones. Phytoplankton produce DMSP as a way to handle osmotic stress; when grazed by zooplankton or lysed by viruses, DMSP is broken down into DMS. Other microbes metabolize sulfur compounds into DMDS, H₂S, and others.

If such a cycle—or something like it—exists on K2-18b, it would suggest a complex biosphere, not just isolated organisms.

But here's the rub: abiotic pathways for these molecules must be explored and excluded. Could volcanic activity, UV-driven chemistry, or some exotic atmospheric process generate DMS or DMDS in a hydrogen-rich atmosphere? Theoretical chemists are scrambling for answers.

So, caution remains the astronomer's motto. The team stresses that while the signal is the strongest yet, non-biological explanations must be thoroughly ruled out before claiming even the possibility of life.

A molecule that, on Earth, rises from algae-covered oceans, has now risen from the atmosphere of a distant world. Whether this is truly life, or an undiscovered quirk of chemistry, remains to be seen.

But for the first time, astronomy is starting to smell like biology.

REFERENCES

Srila W, Sripilai K, Binlateh T, Thammanichanon P, Tiskratok W, Noisa P, Jitprasertwong P. Relationship Between the Salivary Microbiome and Oral Malodor Metabolites in Older Thai Individuals with Periodontitis and the Cytotoxic Effects of Malodor Compounds on Human Oral Squamous Carcinoma (HSC-4) Cells. Dentistry Journal. 2025 Jan 16;13(1):36.

Dekeirsschieter J, Stefanuto PH, Brasseur C, Haubruge E, Focant JF. Enhanced characterization of the smell of death by comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GCxGC-TOFMS). PLoS One. 2012;7(6):e39005. doi: 10.1371/journal.pone.0039005. Epub 2012 Jun 18. PMID: 22723918; PMCID: PMC3377612.

Madhusudhan, Nikku; et al. (March 2020). "The Interior and Atmosphere of the Habitable-zone Exoplanet K2-18b". The Astrophysical Journal Letters. 891 (1). L7. arXiv:2002.11115. doi:10.3847/2041-8213/ab7229

Schmidt SP, MacDonald RJ, Tsai SM, Radica M, Wang LC, Ahrer EM, Bell TJ, Fisher C, Thorngren DP, Wogan N, May EM. A Comprehensive Reanalysis of K2-18 b's JWST NIRISS+ NIRSpec Transmission Spectrum. arXiv preprint arXiv:2501.18477. 2025 Jan 30. arXiv:2501.18477 [astro-ph.EP] https://doi.org/10.48550/arXiv.2501.18477

Ma J, Han Y, Ge J, Wen L, Ma C, Qi Y, Volmer DA. Comprehensive Two‐Dimensional Gas Chromatography–Mass Spectrometry for the Analysis of Atmospheric Particulate Matter. Rapid Communications in Mass Spectrometry. 2025 Jul 15;39(13):e10034.

The Invisible Scent: Gut Microbes, Metabolism & MEBO

2025-04-03T12:44:00.000-07:00

Welcome to The Invisible Scent, the podcast on the hidden connections between gut bacteria, metabolism, and socially debilitating malodor conditions like PATM, MEBO and TMAU.

With expert interviews, patient stories, and cutting-edge insights, The Invisible Scent seeks to bridge the gap between medical research and real-world experiences. By embracing patient-reported data and advancing diagnostic tools, we aim to pave the way for more effective treatments and better quality of life for those affected.

Overview of MEBO/PATM and TMAU studies

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A EURORDIS and NORD Member Organization

From 4R to 5R: The Evolution of Functional Medicine in Gut Health

2025-02-23T07:50:00.000-08:00

Functional medicine provides a powerful model known as the 5R Approach (Kim, 2024), which builds on the original 4R framework (Remove, Replace, Reinoculate, and Repair; Liška, 2003)) by adding a crucial final step: Rebalance.

This method is particularly valuable in treating gut dysbiosis, a condition in which the ratio of beneficial and harmful bacteria in the intestine is disrupted, leading to inflammation, poor digestion, and systemic health issues. Research has linked gut dysfunction to chronic conditions such as rheumatoid arthritis, eczema, and neurological disorders (Liška, 2003) as well as nonsyndromic body odor (Gabashvili, 2020)

1. Remove: Eliminating Triggers of Gut Dysfunction

The first step in healing the gut is removing harmful elements that contribute to dysbiosis and inflammation. These include:

Pathogens – Overgrowth of harmful bacteria, yeast (Candida), or parasites.

Inflammatory Foods – Processed sugars, refined carbohydrates, artificial additives, and common allergens (gluten, dairy, soy).

Toxins & Medications – Overuse of antibiotics, NSAIDs, and environmental toxins disrupt gut flora and damage the mucosal lining.

📌 An elimination diet can help identify specific food triggers. GI map test as well as testing for known gut infections (such as H.pylori, HSV, CMV, giardia or Candida spp.) can also guide targeted interventions.

2. Replace: Supporting Digestive Function

Once harmful elements are removed, the next step is to restore digestive efficiency by supplying essential compounds for proper digestion:

Digestive Enzymes – Help break down food and enhance nutrient absorption.

Stomach Acid (HCl) – Supports protein digestion and prevents bacterial overgrowth.

Bile Salts – Assist in fat digestion and absorption, especially if gallbladder function is compromised.

📌 Consider incorporating enzyme-rich foods like papaya (papain) and pineapple (bromelain) or taking targeted supplements.

3. Reinoculate: Restoring Beneficial Bacteria

A diverse microbiome is essential for digestion, immunity, and gut-brain interactions. Research suggests that early-life gut health, influenced by factors like breastfeeding, can impact long-term microbial balance (Ley et al., 2021).

📌 Aim for a variety of fiber-rich foods, prebiotics (asparagus, bananas, onions) and probiotic-rich fermented foods to support microbiome diversity, rather than relying solely on probiotic supplements.

4. Repair: Healing the Gut Lining

An increase in harmful bacteria can damage the intestinal mucosal cells, contributing to leaky gut syndrome and systemic inflammation (Kim, 2024). Repairing the gut lining is crucial for long-term resilience.

Key nutrients that aid gut repair include:

L-glutamine – An amino acid essential for intestinal wall regeneration.

Collagen & Bone Broth – Provide glycine and proline, which strengthen the gut barrier.

Zinc & Vitamin A – Promote mucosal healing and immune function.

Omega-3 Fatty Acids – Reduce inflammation and support tissue repair.

5. Rebalance: Addressing Lifestyle Factors

The final and often overlooked step in gut healing is rebalance—restoring the mind-body connection and lifestyle habits that influence digestive health. The gut-brain axis plays a crucial role in regulating digestion, with parasympathetic “Rest and Digest” responses supporting motility and secretions (Gantzer, 2021).

To rebalance:

Stress Management – Chronic stress disrupts gut function and increases inflammation. Practices like meditation, deep breathing, and yoga enhance parasympathetic regulation.

Sleep Quality – Poor sleep affects gut motility and microbiome balance. Aim for 7-9 hours of uninterrupted sleep.

Physical Activity – Moderate exercise supports gut health by improving motility and microbiome diversity.

📌 Engage in mindful eating—slow down, chew thoroughly, and avoid distractions to support optimal digestion.

The 5R Approach offers a structured, evidence-based method for restoring gut health and preventing chronic disease. Whether dealing with digestive disorders, autoimmunity, or general well-being, this framework provides a sustainable path to healing.

By removing harmful triggers, replacing digestive supports, reinoculating the microbiome, repairing the gut lining, and rebalancing lifestyle factors, we can achieve long-term gut resilience and overall health.

REFERENCES

Gabashvili IS Cutaneous Bacteria in the Gut Microbiome as Biomarkers of Systemic Malodor and People Are Allergic to Me (PATM) Conditions: Insights From a Virtually Conducted Clinical Trial JMIR Dermatol 2020;3(1):e10508 doi: 10.2196/10508

김규남. 기능의학적 5R 치료의 근거와 적용. Journal of Korean Institute for Functional Medicine. 2024 May;7(1):1-8: Kyu-Nam Kim Korean Society of Functional Medicine Journal of Korean Institute for Functional Medicine Vol.7 No. 1 2024.05 1 - 8 (8 pages) DOI : 10.32581/jkifm.2024.7.1.1

Liska DJ, Lukaczer D. Gut dysfunction and chronic disease: the benefits of applying the 4R GI restoration program. ANSR-Appl Nutr Sci Rep. 2003:1-8.

J. Gantzer Acta Supporting Gut Health by Homeostasis and Intrinsic Mechanisms. Scientific Neurology 1 November 2021 https://www.actascientific.com/ASNE/pdf/ASNE-04-0444.pdf

Sniffing Out Stress: Odor Profiling as a Tool for Health Monitoring

2024-12-31T19:44:00.000-08:00

Recent research paper highlights the potential of manure odor profiling as a non-invasive tool for monitoring stress and intestinal health in poultry flocks. Using advanced gas chromatography-mass spectrometry, scientists analyzed volatile compounds in manure from layer pullets undergoing routine vaccinations, such as Salmonella and viral/bacterial vaccine cocktails. These vaccinations served as model stressors.

Key findings include:

Age Matters: Young and older pullets displayed distinct volatile profiles. Compounds like beta-camphor and (Z)-6-Tridecene were elevated in younger birds, while carbonyl sulfide and trimethylamine dominated in older ones.
Vaccine Impact: The Salmonella vaccine elicited the most consistent changes in manure volatiles, particularly in younger birds, while the viral/bacterial cocktail caused more pronounced shifts in older birds.
Consistency: Despite differences in age, housing, and vaccine type, reductions in certain volatile intensities (e.g., (Z)-6-Tridecene) were observed in three of four flocks post-vaccination.

This approach could pave the way for precision livestock farming, offering an objective means of monitoring flock-level responses to stressors and intestinal health challenges.

Interestingly, trimethylamine (TMA)—a volatile compound detected in older pullets—plays a significant role in both poultry manure profiling and human health. Recent research identified the bacterium JAGTTR01 sp018223385 as a key player in producing TMA from L-carnitine in the human gut. Elevated TMA levels, when metabolized into trimethylamine N-oxide (TMAO), are linked to cardiovascular risks.

The overlap underscores the broader potential of olfactory diagnostics in understanding microbial activity and health impacts across species. Whether in poultry farms or human health, volatile profiling reveals a fascinating connection between microbial metabolism, diet, and well-being.

REFERENCES

van Veen LA, van den Brand H, van den Oever ACM, Kemp B, Meisenburg M. Manure odor profiling for flock-level monitoring on commercial layer pullet farms: Vaccination events as a model stressor. Poult Sci. 2024 Dec 16;104(2):104681. doi: 10.1016/j.psj.2024.104681. Epub ahead of print. PMID: 39721281.

Wu WK, Lo YL, Chiu JY, Hsu CL, Lo IH, Panyod S, Liao YC, Chiu THT, Yang YT, Kuo HC, Zou HB, Chen YH, Chuang HL, Yen JJY, Wang JT, Chiu HM, Hsu CC, Kuo CH, Sheen LY, Kao HL, Wu MS. Gut microbes with the gbu genes determine TMAO production from L-carnitine intake and serve as a biomarker for precision nutrition. Gut Microbes. 2025 Dec;17(1):2446374. doi: 10.1080/19490976.2024.2446374. Epub 2024 Dec 26. PMID: 39722590.

PATM and Its Unbearable Reality

2024-12-12T12:48:00.000-08:00

Condition that lacks a formal name can isolate you from the world.

Josephine Franks brings to light the deeply isolating and misunderstood world of those living with PATM. This phenomenon causes people in proximity to sufferers to develop hay fever-like symptoms, including coughing, sneezing, and itchy eyes.

Franks shares the stories of individuals like Medinah, a young woman whose condition confines her largely to her home, and Fahima, who has adapted her lifestyle to avoid triggering reactions in others. These personal accounts reveal the immense physical, emotional, and social toll of PATM. Sandra, a long-time sufferer, describes how the condition has led to anxiety, depression, and career setbacks, while Amir openly speaks about the profound loneliness and mental health challenges he faces.

While the article does not address our microbiome and metabolome findings, investigations by our scientists have uncovered significant heterogeneity in sufferers, complicating the search for patterns or consistent biomarkers. Communicating our research findings to the broader scientific community and securing adequate attention remain major hurdles.

Read the full article to learn more about the challenges, resilience, and some prior science surrounding this enigmatic condition: Read Josephine Franks's article on Sky News.

A EURORDIS and NORD Member Organization

Exhale The Difference: Propylene Oxide as a Game-Changer in Identifying Idiopathic Malodor Conditions

2024-04-13T13:41:00.000-07:00

A new study posted on MedrXiv sheds light on the potential of breath analysis as a powerful, non-invasive diagnostic tool for Trimethylaminuria (TMAU) and TMAU-like conditions. One of the most interesting observations is the detection of Propylene Oxide in exhaled breath suggesting its delayed elimination and offering a promising marker for misunderstood and underdiagnosed conditions.

TMAU-like (yet negative to choline-challenge-based test) and "People Are Allergic To Me" (PATM) conditions, characterized by the emission of odorous or irritating Volatile Organic Compounds (VOCs), have long challenged the medical community due to the lack of non-challenge-based diagnostic procedures.

Using advanced gas chromatography-mass spectrometry, researchers analyzed the breath of 23 individuals exhibiting TMAU-like symptoms. They discovered that Propylene Oxide, alongside other VOCs, some of which were previously associated with PATM, can effectively discriminate between individuals who have tested positive for TMAU at some point and those who have not. This method demonstrated impressive accuracy, precision, and recall rates, making it a potential cornerstone for future diagnostic strategies.

Propylene Oxide's presence in breath samples particularly stood out in the study. This compound was more abundant in individuals that never tested positive for TMAU, potentially pointing to unique metabolic processes or environmental interactions that could be pivotal in understanding and managing TMAU-like conditions.

Propylene Oxide (PO) is a prevalent chemical found not only on Earth, owing to its widespread use in industrial and consumer applications, but also in the Milky Way. It leaves more significant marks on the human body than previously thought. Mass production contributes to its omnipresence, and exposure can occur through various sources such as cellulose acetate film, wood shavings, and paper cups. Despite efforts to eliminate gas residues, accidental exposure still occurs, particularly among workers involved in sterilization processes. Additionally, foods treated with PO as a fumigant may contain residues of the chemical.

PO has been detected in human breath following exposure to Propylene (PE), a combustion product found in forest fires, cigarette smoke, and vehicle exhaust. Indoor exposure is typically higher than outdoors due to residential activities like cooking, and urban areas tend to have higher concentrations than rural regions. Workers in specific industries may face elevated exposure levels, such as firefighters and refinery plant operators. PEG in cosmetic products can also be contaminated with propylene oxide. Furthermore, Propylene Glycol (PG) in cigarettes and e-liquids can be converted to PO, contributing to exposure.

Other compounds mentioned in the paper were markers of oxidative stress Hydroperoxide, hexyl; Hexanal; Decane, 2-methyl-; Tetradecane; Decane, 2,6,6-trimethyl- and D-limonene. 2,2,3-trimethylnonane was one of compounds associated with breath odor.

This research emphasizes the need for personalized diagnostic approaches, considering the significant variability in VOCs among individuals. Such tailored strategies could lead to more accurate diagnoses and better management of conditions that currently lack specific treatments.

REFERENCES

Irene S. Gabashvili 2024 Propylene Oxide in Exhaled Breath as a Marker for Discriminating TMAU-like Conditions from TMAU medRxiv 2024.04.11.24305677; doi: https://doi.org/10.1101/2024.04.11.24305677

Irene S. Gabashvili 2024 Biological Factors Influencing Individual Responses to Propylene Oxide: A Systematic Review of Exogenous Exposure, Endogenous Production and Detoxification

medRxiv 2024.02.15.24302622; doi: https://doi.org/10.1101/2024.02.15.24302622

Open-Source Project: OSF | Biological Factors that Influence Individual Responses to Environmental Epoxides DOI 10.17605/OSF.IO/W7682

The Invisible Language of Nature

2024-01-21T15:15:00.000-08:00

Chemical communication, an invisible yet powerful dialogue within the natural world, plays a crucial role in the interactions between different species. One fascinating aspect of this is the concept of kairomones, chemicals emitted by one species that beneficially affect another, often at the emitter's expense. Unlike pheromones, which influence the same species, kairomones involve cross-species interactions.

Kairomones are a subtle yet potent force in nature's complex web. For example, human kairomones can significantly influence mosquito behavior. When humans exhale, they release carbon dioxide, L-(+)-lactic acid, and ammonia, unwittingly signaling their presence to mosquitoes. This chemical signal is a dinner bell for these insects, guiding them to their next blood meal. This interaction, while advantageous for the mosquito, is a clear disadvantage for humans, particularly considering the role mosquitoes play in transmitting diseases.

The study of human kairomones opens a window into understanding and potentially controlling mosquito populations. A recent study highlighted the potential of geraniol in reducing mosquito attraction by 69-78% to a mixture of key human kairomones like carbon dioxide, L-(+)-lactic acid, and ammonia.

This chemical dialogue extends beyond animals to the plant kingdom. Plants, though lacking a nervous system or traditional senses, have their own form of communication, often mediated by chemicals. For instance, when a plant is under attack, it can release volatile compounds to attract predators of the herbivores harming it. Interestingly, these chemicals can also alert nearby plants of potential danger.

A case study involving sagebrush and wild tobacco plants provides insight into this phenomenon. When sagebrush is damaged, it releases methyl jasmonate, a volatile compound that nearby tobacco plants detect, triggering an increase in their production of defensive agents. This chemical warning system, however, seems to have a very limited range.

The study of chemical communication in nature, whether between humans and mosquitoes or among plants, is an ongoing journey of discovery. It reveals the intricate and often hidden ways in which life on Earth interacts and adapts. As research continues, we may find more innovative ways to apply this knowledge, from controlling pests to understanding ecosystem dynamics.

Chemical communication remains a fascinating and largely uncharted frontier, offering a glimpse into the sophisticated and silent language of nature.

REFERENCES

Coutinho-Abreu IV, Jamshidi O, Raban R, Atabakhsh K, Merriman JA, Akbari OS. Identification of human skin microbiome odorants that manipulate mosquito landing behavior. Sci Rep. 2024 Jan 18;14(1):1631. doi: 10.1038/s41598-023-50182-5. PMID: 38238397; PMCID: PMC10796395.

Karban R, Shiojiri K, Huntzinger M, McCall AC. Damage-induced resistance in sagebrush: volatiles are key to intra- and interplant communication. Ecology. 2006 Apr;87(4):922-30. doi: 10.1890/0012-9658(2006)87[922:drisva]2.0.co;2. PMID: 16676536.

Chemical & Engineering News: Critter Chemistry - Plants to Bugs: Buzz Off! (acs.org) by Sophie Wilkinson, Chemical & Engineering News, American Chemical Society

The short film "Descendants" provides a creative exploration of nature's interconnectedness: http://vimeo.com/8642276

https://entomology.ucdavis.edu/people/richard-karban

https://swissplantscienceweb.unibas.ch/en/farmer/

https://www.ice.mpg.de/person/111845

Rare Diseases in the Era of High-Cost Drug Development

2023-11-13T08:31:00.000-08:00

We are currently witnessing a remarkable era in medical innovation, marked by rapid advancements and transformative developments. Yet the medical community is often unable to tell what works and what doesn’t. As the complexity of medical treatments increases, the importance of distinguishing reliable therapies from ineffective ones becomes ever more crucial. In this context, robust data collection and sophisticated analysis are indispensable tools.

In recent years, the trend in clinical trials has shifted towards smaller studies focusing on diseases that either attract substantial health insurance reimbursements or predominantly affect affluent populations. This shift is largely driven by the expectation of high drug prices post-development. However, this leaves a significant gap in research and treatment for conditions like Metabolic Body Odor (MEBO) and "People are allergic to me" (PATM). These conditions disproportionately impact individuals who may find it challenging to achieve financial security due to the nature of their ailments.

In 2008, a community survey by pharmacist Arun Nagrath highlighted a lack of confidence in medical advice among patients. Fast forward to the present, and while medical practitioners may exhibit greater confidence, their assurance is not always underpinned by evidence. This is evident in the prescription of costly tests, which clinicians may struggle to interpret or follow up effectively.

The landscape of self-treatment is continuously evolving. Popular remedies change over time, and the effectiveness of these treatments varies widely. In 2008, probiotics and Chlorophyl/Copper Chlorophyllin products were at the forefront. However, some patients reported that their odor issues worsened after using these remedies (as indicated by the red area in the corresponding pie chart, compared to green for effectiveness and gray for uncertainty). Many patients found that perfumed products exacerbated their condition, including about half of reported deodorants, though the other half was suitable types. Remedies once popular, like Mushroom extracts such as ProM and Champex, Activated Charcoal, Baking Soda and Hydrogen Peroxide have faded from the discussion. Vitamin B2, although used by fewer than a quarter of respondents in 2008 and found effective by some, remains a favored treatment. Oldenlandia and Coconut oil were found useful by small fraction of respondents. Somebody even used Bleach to clean themselves and found it to make things worse. Interestingly, certain drugs intended for other conditions were reported to have secondary effects on odor – beneficial in cases like Prilosec and Probathine, and detrimental with Anxiolytics, Antidepressants, and Antivirals, the latter aligning with recent findings related to the COVID-19 vaccine. Antifungals were used by a few and were never found to worsen condition. Neither did Folic acid, Zinc, Calcium and Magnesium. There were cases when digestive enzymes, contraceptives, and baking soda treatments made things worse.

Interest in resveratrol, a compound present in red wine, reached its zenith in the late 2000s and early 2010s. During this period, the MEBO community extensively used and promoted this compound. In the mid-2010s, DMB became a focal point of discussion for many, while Fluxovas entered the scene and began to be mentioned starting in 2020.

While the popularity of probiotics endures, there is a noticeable shift towards personalization. Individuals are increasingly acknowledging the significance of identifying probiotic strains that harmonize with their unique physiology and health objectives. Our microbiome study unveiled that individuals with higher cutaneous bacteria (and total bacteria) abundances in the gut benefited from reducing microbial diversity and overall bacterial counts. In contrast, those with lower abundances found advantages in increasing microbial diversity. This highlights the absence of a universal solution for probiotics.

This evolving self-treatment scenario emphasizes the pivotal role of precision medicine, considering individual genetic, environmental, and lifestyle influences for disease treatment and prevention. Conditions like TMAU, MEBO, and PATM, lacking standardized effective treatments, emphasize the pressing need for more nuanced and targeted approaches.

Precision medicine, gaining popularity, particularly in tandem with Artificial Intelligence approaches this year, marks a departure from one-size-fits-all strategies. It relies extensively on data, specifically genomic, microbiome, and metabolomic data, to tailor treatments to individual patient needs. This patient-centric approach promises to revolutionize treatment strategies, especially for those with previously under-researched and underserved medical conditions.

MEBO's causes remain largely unknown, and without clear diagnostic criteria, it is often referred to as idiopathic malodor. This uncertainty mirrors the earlier challenges in diagnosing conditions like IBS, which was once seen as a diagnosis of exclusion. Today, the importance of ruling out other diagnoses through tests is recognized.

MEBO is a poignant example of a rare condition that can severely impact an individual's ability to pursue a career and achieve financial success. This condition is not only socially debilitating but also lacks effective diagnostic and treatment options. Diagnostic studies for such rare conditions are prohibitively expensive, and the lack of effective therapies exacerbates the problem. Moreover, the large heterogeneity within the patient population makes finding a one-size-fits-all solution particularly challenging.

So, what should be done in this scenario? First and foremost, there's a need for increased funding and research attention towards rare diseases like MEBO. This could be facilitated by incentivizing pharmaceutical companies through tax breaks or grants to undertake research in less profitable but socially significant areas.

Secondly, fostering collaborations between research institutions, pharmaceutical companies, and patient advocacy groups can create a more holistic approach to understanding and treating these conditions. Such collaborations can also help in the collection of more comprehensive and diverse data, and better ways to collect it, which is crucial given the heterogeneity of conditions like MEBO.

Thirdly, the role of government and healthcare policymakers is critical. They can implement policies that encourage research and development in neglected areas, ensuring that the healthcare system is inclusive and caters to all, regardless of the financial implications or rarity of the condition.

Lastly, leveraging technology and innovation in medical research can also provide new avenues for diagnosis and treatment. For example, artificial intelligence and machine learning could be used to better understand complex conditions like MEBO, potentially leading to more effective and personalized treatments.

So far there’s never been any real emphasis on making clinical trials better or easier to conduct. Our goal, as a society, seems to be to manufacture more and more sports cars and to drive them faster and faster into the mud.

We hope that the healthcare industry and policymakers work together to ensure that all patients, regardless of their financial status or the rarity of their condition, have access to the treatments they need.

REFERENCES

This is biology's century. We're not ready for it (statnews.com)

Better Trials. Someday. | Science | AAAS

Gabashvili IS. The Incidence and Effect of Adverse Events Due to COVID-19 Vaccines on Breakthrough Infections: Decentralized Observational Study With Underrepresented Groups. JMIR Form Res. 2022 Nov 4;6(11):e41914. doi: 10.2196/41914. PMID: 36309347; PMCID: PMC9640199.

Gabashvili IS. Cutaneous bacteria in the gut microbiome as biomarkers of systemic malodor and People Are Allergic to Me (PATM) conditions: insights from a virtually conducted clinical trial. JMIR Dermatol. 2020 Nov 4;3(1):e10508. doi: 10.2196/10508. https://derma.jmir.org/2020/1/e10508/

Gabashvili IS. Artificial Intelligence in Biomedicine: Systematic Review

medRxiv 2023.07.23.23292672; doi: https://doi.org/10.1101/2023.07.23.23292672

Cytochromes P450 and the World of Volatile Organic Compounds

2023-11-03T14:01:00.000-07:00

Cytochrome P450, often abbreviated as CYP450 (CYP) or simply P450, is a vital group of enzymes found in the liver, and it plays a fundamental role in detoxifying the body and metabolizing various foreign compounds.

Metabolic enzymes employ different catalytic mechanisms. FMOs, for instance, directly receive electrons from nictinamide adenine dinucleotide phosphate (NADPH), while CYPs obtain their electrons via an intermediary protein known as CYP reductase. Furthermore, CYPs activate oxygen only after binding to an oxygenatable substrate, adding an extra layer of complexity to the metabolic puzzle.

In the complex world of enzymatic metabolism, our comprehension of the comparative efficiency of different enzymes remains somewhat limited. The body's selection of which metabolic enzymes to use is governed by several factors such as substrate specificity, enzyme efficiency, temperature and the surrounding environment in the compartment where the enzyme and substrate are in, co-factors and co-enzymes, concentration of substrates and competition for substrates.

Cytochrome P-450 (CYP450) enzymes and Flavin-containing monooxygenases (FMOs), such as FMO3, often participate in the metabolic processes of the same compounds. For instance, substances like Nicotine, Caffeine, Tazarotenic acid, Benzydamine, and the antipsychotic drug Perazine (PER) encounter these enzymes during their metabolic journey.

FMO3, in particular, stands out for its remarkable ability to convert trimethylamine (TMA) into trimethylamine N-oxide (TMAO). However, even TMA navigates a maze of metabolic pathways and could encounter cytochromes P-450.

Similar to FMO3, genetic variations in CYP2E1, such as the SNP g.50657948 T>G, have been linked to odor (lamb odor and flavor in sheep), indicating a broader role beyond metabolism, potentially affecting odorant and pheromone clearance. Ubiquitous amino acid derived from food - tryptophan serves as the precursor for skatole, and the conversion of tryptophan to skatole involves the action of enzymes, including CYP2E1, in a series of metabolic reactions. CYP2E1 expression levels have been correlated with a variety of dietary and physiological factors, such as ethanol consumption, diabetes, fasting, and obesity.

Poor dietary choices, medications, exposure to external factors such as air pollution, cigarette smoke, radiation (e.g., UV radiation from the sun), and certain environmental toxins, inflammatory processes, whether due to infection, injury, or chronic inflammatory conditions, even normal metabolic processes can generate reactive oxygen species (ROS) as byproducts. Examples are superoxide anion (O2·-), hydrogen peroxide (H2O2), hydroxyl radical (·OH), and singlet oxygen (1O2), among others. Excessive production or impaired elimination of ROS can lead to oxidative stress.

To counteract the harmful effects of oxidative stress, the body activates the detoxification process, in which cytochrome P450 takes center stage. Cytochrome P450 catalyzes the addition of an oxygen atom to foreign compounds, making them more water-soluble. This transformation results in the formation of alcohols and, as byproducts, aldehydes. The detoxification process is a critical defense mechanism that helps the body eliminate harmful substances.

High-fat and high-protein diets have gained popularity but can have adverse effects on our health. Research has shown that these diets may induce organ damage, abnormal serum biochemical indexes, and inflammation. Interestingly, the production of malodorous gas compounds in the body because of these diets can be influenced by the interaction between the intestinal microbiota and liver cytochrome P450.

from Zhang et al, 2022

Chemicals that alter xenobiotic metabolizing enzymes, such as CYPs, may also alter endogenous hormone levels since some of these enzymes control levels of endogenous hormones. Many of the pesticides that caused mammary gland tumors or other mammary effects also alter steroidogenesis in the H295R adrenocortical carcinoma cell line, activate nuclear receptors or CYP enzymes, or are estrogenic.

CYP family of heme monooxygenase enzymes is known for its ability to catalyze enantioselective hydroxylation and epoxidation reactions. Epoxidation reactions have been hypothesized to proceed via multiple mechanisms involving different reactive intermediates. A study of the bacterial enzyme CYP199A4 from Rhodopseudomonas palustris demonstrated a significant reduction in epoxidation activity when the D251N mutation was introduced. Remarkably, despite these mutations, the chemoselectivity and stereoselectivity of the epoxidation reaction remained intact.

Innovations in biotechnology have led to the development of specialized cytochrome P450 enzymes, such as the Cytochrome P450 BM-3 mutant (139-3). This mutant exhibits high activity towards the epoxidation of non-natural substrates, including propylene, which can be converted to propylene oxide.

In summary, cytochrome P450 is a fascinating and essential component of our body's biochemistry, with implications that extend beyond detoxification. Understanding its functions and interactions can pave the way for advancements in both medicine and biotechnology.

REFERENCES

Zhang T, Xie B, Liu H. High-fat and high-protein diets from different sources induce different intestinal malodorous gases and inflammation. Food Research International. 2022 Apr 1;154:110989.

Padwa A, Murphree SS. Epoxides and aziridines-a mini review. Arkivoc. 2006 Jan 1;3(6).

Störmer E, Brockmöller J, Roots I, Schmider J. Cytochrome P-450 enzymes and FMO3 contribute to the disposition of the antipsychotic drug perazine in vitro. Psychopharmacology. 2000 Sep;151:312-20.

Harahap RS, Noor RR, Gunawan A. Effect of CYP2E1 gene polymorphisms on lamb odor and flavor in Indonesian sheep. InIOP Conference Series: Earth and Environmental Science 2021 Jun 1 (Vol. 788, No. 1, p. 012022). IOP Publishing.

The Power of Scent: Synthetic Odorants and Hair Health

2023-10-21T17:22:00.002-07:00

In a study published this month in the Journal of Dermatological Science, Edelkamp and a team of researchers have unveiled a novel approach to managing the human hair follicle microbiome. The key player is a synthetic odorant that mimics the scent of sandalwood, known as Sandalore®.

The study's foundation lies in the discovery that human scalp hair follicles (HFs) possess olfactory receptors, which enable them to engage in chemosensation. Specifically, activation of olfactory receptor family 2 subfamily AT member 4 (OR2AT4).

One of the findings was the role of Sandalore® in up-regulating the expression of dermcidin (DCD) within the hair follicles. Previously believed to be exclusively produced by sweat and sebaceous glands, DCD is a potent antimicrobial peptide. The study revealed that synthetic odorant treatment triggered the production of DCD within the hair follicles.

To thoroughly understand the implications of this discovery, the researchers compared DCD expression between fresh-frozen scalp biopsies and microdissected, full-length scalp HFs. These HFs were organ-cultured under various conditions, including the presence or absence of Sandalore®, antibiotics, and the competitive OR2AT4 antagonist, Phenirat®.

Sandalore®-conditioned medium, with increased DCD content, was found to favor the growth of beneficial bacteria, such as Staphylococcus epidermidis and Malassezia restricta, while simultaneously exhibiting antimicrobial activity against Cutibacterium acnes.

The study opens doors for further exploration into using cosmetic odorants in the management of folliculitis and dysbiosis-associated hair diseases.

REFERENCE

Edelkamp J, Lousada MB, Pinto D, Chéret J, Calabrese FM, Jiménez F, Erdmann H, Wessel J, Phillip B, Angelis M, Rinaldi F, Bertolini M, Paus R. Management of the human hair follicle microbiome by a synthetic odorant. J Dermatol Sci. 2023 Oct 17:S0923-1811(23)00221-9. doi: 10.1016/j.jdermsci.2023.09.006. Epub ahead of print. PMID: 37858476.

Methanethiol: The Scent of Disease and Discovery

2023-10-04T17:48:00.007-07:00

In a previous blog post, we discussed the role of SELENBP1 in nonosyndromic (monosymptomatic) halitosis. We learned that if this enzyme isn't functioning correctly, it can lead to the release of more Methanethiol, a volatile and rather unpleasant-smelling gas often associated with the aroma of rotten cabbage.

However, Selenium binding protein 1 (SELENBP1) isn't just a casual bystander in our biological processes. It has been linked to various health conditions and diseases. These include:

Hypermethioninemia: A rare condition that can sometimes come with learning disabilities and neurological issues.

Schizophrenia: a complex mental disorder that challenges our understanding of the human mind

Hypertension and Ischemic Heart Conditions, conditions such as Guillain-Barré syndrome and Infectious Diseases: Dysregulation of SELENBP1 is associated with Zika virus (ZIKV) and dengue infections, as well as COVID-19.

SELENBP1's role in several types of cancer, including its downregulation at the onset of cancer and upregulation in later stages, is a subject of intense research.

Methanethiol contributes to the distinct scent signature linked to cancer, characterized by a combination of volatile organic compounds (VOCs). Researchers are increasingly exploring this intriguing scent profile as a potential tool for non-invasive early cancer diagnosis.

Methanethiol is a testament to the intricate connections between genetics, metabolism, and disease, reminding us that even the smelliest molecules can lead to groundbreaking discoveries.

Methanethiol also contributes to the distinct scent signature associated with cancer, characterized by a combination of volatile organic compounds (VOCs). This intriguing scent profile is increasingly being explored for non-invasive early cancer diagnosis.

In a recent paper titled "Methanethiol: A Scent Mark of Dysregulated Sulfur Metabolism in Cancer," researchers unveiled new findings:

Tumor cells undergo metabolic adaptations to meet increased energy demands and enhance stress resilience. This includes dysregulation of sulfur metabolism and elevated levels of volatile sulfur compounds (VSCs) in cancer patients.

Methanethiol stands out as the predominant cancer-associated VSC and is being considered as a potential biomarker for non-invasive cancer diagnosis.

Within the gut microbiome of colorectal carcinoma (CRC) patients, gut bacteria, particularly methanethiol-producing strains like Fusobacterium nucleatum, are a significant source of exposure to methanethiol.

Selenium-binding protein 1 (SELENBP1) plays a crucial role in the rapid degradation of methanethiol through its methanethiol oxidase (MTO) activity.

Odor-based cancer screening methods, such as sniffer dogs and canine scent detection, even human feedback, have shown great promise in identifying lung and colorectal cancer patients, opening doors to non-invasive detection approaches.

The dysregulation of sulfur metabolism and the potential use of methanethiol as a biomarker, coupled with the innovative odor-based cancer screening methods, offer not just promising but transformative avenues for non-invasive cancer detection and cutting-edge research.

REFERENCE

Philipp TM, Scheller AS, Krafczyk N, Klotz LO, Steinbrenner H. Methanethiol: A Scent Mark of Dysregulated Sulfur Metabolism in Cancer. Antioxidants (Basel). 2023 Sep 19;12(9):1780. doi: 10.3390/antiox12091780. PMID: 37760083; PMCID: PMC10525899.

Chronicles of Community-Driven Research: The Evolution of MEBO and PATM Studies

2023-08-26T13:02:00.056-07:00

In the ever-evolving landscape of medical science, the untangling of medical mysteries often hinges not just on technological advancements or expert researchers, but on the active involvement of community members. Community efforts have been instrumental in the identification and understanding of elusive conditions MEBO (Metabolic Body Odor) and PATM (People Are Allergic to Me).

Late 1990s - early 2000s: The Dawn of Online Support Forums

Before the conditions were officially named, online forums like MSN Body Odor Support Forum, ibsgroup.org, Yahoo TMAU group, and Curezone BO & Halitosis and TMAU forums served as early platforms for sufferers to discuss their symptoms.

At this time, Trimethylaminuria (TMAU) was a scarcely recognized condition, and diagnostic tests were both costly and geographically limited. Trimethylaminuria support group, later established as foundation raises 35K and awards it to Dr. George Preti of Monell Center, the world’s only independent, non-profit scientific institute dedicated to interdisciplinary basic research on the senses of taste and smell.

2006-2007: Birth of MEBO and PATM Communities

In 2006, the acronym "PATM" was first coined by a sufferer, and by 2007, a dedicated PATM community was established on MedHelp. The initial post was reposted in PATM forum and garnered over 8,800 responses, signifying the start of a community-led initiative to explore the condition. While the term FBO (fecal body odor) emerged earlier and is still used on online forums, it is often avoided due to its less appealing connotation. MEBO was coined by another individual suffering from a similar undiagnosed condition. This further fueled community-driven research and knowledge sharing among those affected.

2008: Broadening the Dialogue

The blog Bloodbornebodyodorandhalitosis.com is launched, later transitioned to meboblog.com. This year also saw more in-person meetups and community surveys, including one by pharmacist Arun Nagrath that received about 100 responses. 95% of responders was trying to seek medical help, over 90% thought that their doctor was not knowledgeable nor confident in their recommendations.

2009: Formalizing Research Efforts

MEBO Research Charity was founded in both the UK and Florida, spearheaded by Maria de la Torre. The first collaborative study with UK's Biolab was initiated, focusing on blood and urine tests. The results were subsequently published on the MEBO blog and clinicaltrials.gov (NCT02692495, principal investigator: Irene Gabashvili).

2010: Unveiling the Microbiome and Genetic Factors

At MEBO's 1st annual conference, held in Nashville, Dr. Gabashvili presents "Microbes and us," discussing the human microbiome's role in poorly understood conditions like idiopathic malodor and multiple chemical sensitivities (MCS). Previously, MEBO interviewed Metametrix about their GI Effects panel, which measured stool bacteria, fungus, and parasites with DNA analysis. Metametrix, pioneer in diagnostics of nutritional insufficiencies and metabolic dysfunction,was later acquired by Genova Diagnostics.

Dr. Nigel Manning introduces 12 potential subtypes of TMAU. Out of 1,150 urine samples from 716 individuals collected between 1997 and 2009, 379 (53%) indicate significant TMAU presence. The launch of a new FMO3 genetic testing service promises to provide clearer diagnostic results. Additionally, a TMAU service dog program is initiated.

2011: The Advent of Genomic Data Sharing

Community members begin sharing genomic data, and MEBO critiques the limitations of 23andMe's FMO3 testing in blog posts. Dr. George Preti and his team at the Monell Center publish "Individuals reporting idiopathic malodor production: demographics and incidence of trimethylaminuria", revealing that only one-third of individuals with idiopathic malodor test positive for TMAU. New study from Oxford, proposes two genes coding enzymes, besides FMO3, NAT8 and PYROXD2, both with relatively uncharacterized functional roles, as potentially linked to TMAU.

The second annual meetup in Washington, DC, focuses on the interplay between genetic mechanisms and holistic health. Skype conference call group is formed.

2012: Empowering Patients Through Technology

A new MEBO study focusing on alveolar breath is initiated (NCT03451994). Aurametrix health management software is publicly launched, allowing patients to diagnose metabolic inefficiencies through digital food and symptom journaling. Karen James, MEBO UK’s Public Relations Director, publishes an article in the Royal College of General Practitioners (RCGP) journal InnovAiT, describing the life of a TMAU sufferer. For iGEM competition, student team from Fatih university genetically engineers bacteria producing geraniol and FMO3 to eliminate TMA odors. Their product, FreshEcoli, is supposed to work as a synthetic perfume.

The Third Annual Meetup in Miami Beach features Dr. Elizabeth Shephard discussing pharmacogenetics and personalized medicine.

2013: Deepening Theoretical Insights

MEBO UK's scientific director, Dr. Colin Harvey-Woodworth, publishes an article proposing that some MEBO symptoms may be secondary to dimethylsulphidemia, a previously unidentified metabolic condition linked to DMGDH gene (missense mutation in DMGDH was known to be associated with fish odor similar to pyridoxine non-responsive homocystinuria). Concurrently, a mediterranean study reveals that individuals carrying FMO3 mutations may not necessarily experience odor issues. The study finds that the TMA/TMAO ratio in urine samples from individuals with 158KK/308EG variants indicates reduced FMO3 activity, yet these individuals do not exhibit the hallmark fish-like odor commonly associated with trimethylaminuria. This data underscores the notion that the expression of trimethylaminuria symptoms is influenced by factors beyond the presence of specific genetic variants.

2014: Therapeutic Innovations

Dr. Jean-François Brugère proposes the therapeutic use of archaea to prevent trimethylaminuria and cardiovascular disease. The technique was patented but not yet tested in humans. MEBO's TMAU urine testing program is initiated, and the results are discussed. Another student team from Paris University, genetically engineers skin bacteria by introducing a trimethylamine mono-oxygenase from a non-human bacteria Ruegeria pomeroyi, for iGEM competition. Dr. Aydin proposes new definitions for halitosis. Reddit TMAU and PATM groups are created.

2015: Expanding Testing and new molecular targets

The MEBO Conference in Orlando distributes urine test kits based on choline challenges and discusses emerging trends in testing methodologies.

3,3-Dimethyl-1-butanol (DMB), which is a structural analog of choline found in some foods, such as balsamic vinegars, red wines, some cold-pressed extra virgin olive oils and grapeseed oils is demonstrated to inhibit TMA production by gut bacteria. DMB has potential as a therapeutic approach. Studies also show the inhibitory effects of Resveratrol on TMA production in mice, further expanding the scope of potential small molecule targets. Dr Stanley Hazen files a patent.

2016: Streamlining Diagnostic Approaches

MEBO collaborates with Professor David Wishart on a Urine Metabolomics study, registered as NCT02683876, involving Canadian participants. The study aims to explore simpler, non-challenge-based tests for diagnosis.

Several sufferers in the MEBO community report taking Resveratrol for a few months, with excellent results in decreasing or completely eliminating their odor symptoms while increasing consumption of foods high in choline, carnitine, and lecithin.

2017: Diagnostic Breakthroughs and the Social Media Shift

MEBO's Scientific Director, Irene Gabashvili, publishes the Biolab study on BiorXiv. The study reveals significant differences in intestinal permeability among participants based on body regions responsible for VOC emissions. In addition, the study identifies two subgroups of MEBO/PATM sufferers based on sugar intake. Due to the small sample size of 16 participants, the article remains a preprint. Unfortunately, the current structure and incentives of mainstream academic publishing favor well-funded research on common diseases and are less accommodating to research on overlooked rare conditions.

A Monell Center Study published in BMC Medical Genetics delves into the genetic complexities of TMAU, revealing that not all cases are linked to the FMO3 gene. Although the choline challenge test confirmed a diagnosis of TMAU by revealing a high level of urinary TMA in all 10 subjects, genetic analyses revealed that the FMO3 gene appeared to be normal in four of the 10. Additional analyses revealed defects in several other genes that could contribute to the inability to metabolize the odorous TMA. No rare variants are found in PYROXD2 and a DMGDH, but there were associations with BHMT2, SARDH and SHMT1 genes, which directly interact with DMGDH in the gene network and may participate in the same pathway. At MEBO conference in Miami Beach, Professor Shephard talks about microbiome and diet.

Armpit microbiome transplantation shows reduction in odor when performed from one sibling to another.

Danny Kunz and his Citizen Research Group in Germany initiate a DNA sequencing study. Their simulations backed by large enzyme databases suggest that Thyroid-stimulating hormone (TSH) may play a role. Danny proposes a new name for the condition: Intestinal Metabolic Bromhidrosis Syndrome (IMBS).

TMAU UP Podcast is launched on YouTube. Facebook's "Groups" feature spurs the creation of new private MEBO and PATM communities, marking a new era in community engagement and data sharing.

2018-2020: Advancing Research and Understanding

A Microbiome study of MEBO and PATM communities is initiated, registered as NCT02683876.

A Japanese paper confirms PATM as a physical condition connected to skin petrochemicals and microbes. Meanwhile a case report entitled "People allergic to me and body dysmorphic disorder" published in Asian Journal of Psychiatry is linking a case to a relatively common psychiatric disorder characterized by preoccupations with perceived defects in physical appearance. The average age of BDD onset was previously estimated as 15 with symptoms lasting 18 years on average without proper treatment. The prevalence of BDD is thought to be 0.7-2.4% in the general population, but the condition remains underdiagnosed and poorly understood.

Results from the MEBO-Wishart study align with previous MEBO/PATM findings but highlight the limitations of morning urine tests. A new PATM survey is conducted by an independent PATM ufferer/researcher. Average age of responders is 28. Mononucleosis due to CMV is proposed as the cause of PATM.

A UC San Diego student team explores the enzymatic breakdown of TMA. New gene SELENBP1 is proposed to explain metabolic halitosis. A patent on using Mikania plant extract to inhibit the conversion of choline to trimethylamine (TMA) is filed and granted, based on an earlier patent for using this plant to suppress body odor.

RareConnect is established as a platform for those affected by rare diseases, including MEBO Research members. MEBO Research becomes a member. Unfortunately, by the end of 2023 it will be shut down, not being able to compete with Facebook and Reddit. Yahoo Groups shut down on December 15, 2020, for the same reason. New Instagram and WhatsApp groups are created.

New paper "Treatments of trimethylaminuria: where we are and where we might be heading" is published. It reviews Fecal microbial transplantation (FMT) that was not especially successful for reducing TMA or was only transiently effective as the symptoms returned one year after treatment. Antibiotic treatment is also transiently effective in some patients and completely ineffective in others. Future research directions include gene therapy, enzyme replacement/enhancement therapy and gut microbiome modulation.

Peer-reviewed paper examining the microbiome traits of individuals self-identifying with PATM and MEBO (NCT02683876) is published in JMIR Dermatology. The study reveals that both MEBO and PATM share increased levels of malodor-associated skin bacteria compared to non-MEBO/non-PATM groups, correlating with severity of self-reported symptoms. However, both populations exhibit significant heterogeneity.

2021-2023: Ongoing Challenges and Future Directions

A COVID study identifies flare-ups in 10-15% of the MEBO population post-infection and vaccination, possibly related to microbiome and hormonal fluctuations (NCT04832932; peer-reviewed paper published in JMIR Formative Research). COVID-19 has led to the emergence of new cases, with individuals developing MEBO/PATM conditions following infection and/or vaccination.

A cysteine challenge test for hydrogen sulfide production is suggested. Florida State University's iGem team proposes a synthetic biology project for TMAU.

New paper by Chris Callewaert explores various cutting-edge approaches to skin health, including genetically engineered probiotics and microbiome transplantation. While promising, the latter method currently lacks scalability for industrial applications. The paper also delves into skin bacteriotherapy, a technique involving the application of one or multiple pure bacterial cultures with health-promoting properties to cleansed or disinfected skin areas. Additionally, the study examines the use of prebiotics applied directly to the skin to encourage the growth of beneficial microbes. Each of these innovative approaches holds promise but also presents its own set of challenges.

A study by Professor Sekine in Nature Scientific Reports identifies volatile organic compounds as key differentiators between PATM sufferers and controls. These results align with our yet to be published findings from MEBO-Menssana Alveolar Breath Test Study (NCT03451994) and Microbiome study (NCT03582826).

The FSU team introduces their innovative probiotic, E.esperance, at the iGEM competition in Paris on November 2, 2023.

Despite these advancements, mainstream science remains largely uninterested in community-based research, leaving MEBO, PATM and TMAU without a definitive cure.

Human Skin Gas Profiles in PATM

2023-08-20T11:41:00.016-07:00

People Allergic to Me (PATM) is a perplexing condition that has left both sufferers and medical professionals searching for answers. Thousands of individuals worldwide claim to experience PATM, leading to severe mental health challenges such as depression, anxiety, and suicidal tendencies. Despite its far-reaching impact, the underlying causes remain mysterious, with only a few scientific studies dedicated to understanding this condition. While a small subset of PATM sufferers has been diagnosed with TMAU, the majority remain without a diagnosis.

A new study lead by Professor Sekine, recently published in Nature Scientific Reports, explores the human skin gas profiles to shed new light on PATM.

The study included 44 subjects, divided into two groups: 24 without PATM (non-PATM) and 20 with PATM. The non-PATM group involved 13 male and 11 female participants (age: 18–59, 31 ± 13 years old). The PATM group comprised 12 male and 8 female participants (age: 19–53, average 39 ± 12 years old).

The non-PATM group had no known diseases, while the PATM group reported symptoms of PATM without other apparent diseases.

Researchers sought to understand the skin gas profile of people with and without PATM, potentially the source of body odor or other types of emissions. They measured the emission rate of 75 volatile compounds from the skin using a tool called a passive flux sampler (PFS) coupled with gas chromatography/mass spectrometry (GC/MS). PFS was designed to be convenient and unobtrusive, allowing people to use it on the go without any hassle.

Participants in the study were given a PFS device, similar in size to a bottle cap, to collect skin gas samples from their non-dominant forearm. They wore this device for an hour without any restrictions on their activities. The device was easily attached to the skin with a piece of surgical tape and didn't require any special preparation. After collecting the samples, PFS devices were sent to the laboratory and analyzed.

The PATM group exhibited significantly greater emission fluxes for a variety of chemicals, including some with offensive odors, and lower emissions of others, including some with more pleasant or neutralizing smells.

Among the 75 measured skin gases, the PATM group exhibited significantly greater emission fluxes for chemicals like alcohol 2-ethyl-1-hexanol (2E1H), aldehyde isovaleraldehyde, hexanal, acetone, toluene, m,p-xylene, methyl mercaptan, ethyl mercaptan, and allyl methyl sulphide (AMS). These chemicals often have offensive odors and/or can lead to adverse health effects. The emissions of petrochemical 2E1H, and aromatic hydrocarbons (with benzene ring in their structure): toluene, and m,p-xylene were notably higher in the PATM group, with increases of approximately 12, 39, and four times, respectively.

Volatile organosulfur compounds such as methyl mercaptan (fecal odor, resembling smell of rotten cabbage or decaying vegetables), ethyl mercaptan (rotten fish, garlic, or onions), and Allyl Methyl Sulfide (AMS, garlic- or onion-like odor) were also significant. These compounds have extremely low odor thresholds and could easily alter body odor perception in PATM subjects. Bacteria in the oral cavity, such as Porphyromonas gingivalis and Anaerobic bacteria in the gut, such as Desulfovibrio species are producers of Methanethiol.

Isovaleraldehyde contributes to body odor with a pungent fruit-like smell that can also contribute to aroma of beer and cheese. It can be sourced from metabolic breakdown of amino acids like leucine and valine, hence dietary intake, and microbial activity in the gut by methylotrophic yeasts. , species of Clostridium, Actinobacteria (Rhodococcus, Mycobacterium and Gordonia), Proteobacteria (Acetobacterium such as Gluconobacter oxydans), Odoribacteraceae, Ruminococcus gnavus, etc. These microbes are capable of producing Isovaleraldehyde through anaerobic fermentation and the mevalonate-independent glyceraldehyde 3-phosphate/pyruvate pathway.

Greater emission of acetone might indicate eating disorders in the PATM group, as it is influenced by fasting, starvation, or diet.

The PATM group had less skin release of various substances, including some types of alcohols, smell-related chemicals, and fruity-smelling compounds. Some of these chemicals are used in flavors or fragrances and are known to have a relaxing effect.

For example, α-pinene, β-pinene, and D-limonene have antifungal activities as well as abilities to decrease depression-like behavior and improve memory via an anti-neuroinflammatory mechanism under chronic restraint stress.

D-limonene can be consumed through the diet by eating citrus fruits or drinking citrus-flavored beverages. Some fruity-smelling compounds are naturally found in fruits like peach and pineapple and contribute to sweet body scents. It can also be absorbed through the skin from personal care products containing citrus oils or inhaled from air.

Acetic acid smells like vinegar and is made by bacteria breaking down certain substances in sweat. It is linked to body odor in young adults. Lower skin emissions of acetic acid in the PATM group showed that sweating may not be the cause of their unique body odor. Acetic Acid is produced by acetic acid bacteria, such as Acetobacter and Gluconobacter species. Certain lactic acid bacteria, such as Lactobacillus, can also produce acetic acid.

The study also looked at benzaldehyde, which might come from toluene. People with PATM had much more skin emission of toluene but less of benzaldehyde.

The presence of benzaldehyde in the human body is typically at low levels, and its occurrence may vary based on factors such as diet, environmental exposure, individual metabolism, and gut microbiome composition. Almonds, apricots, and cherries are examples of foods that contain benzaldehyde or related compounds. Toluene is a common solvent used in various industrial and household products such as paints, glues, nail polish, and cleaning agents. Inhalation of fumes from these products can lead to toluene being present in the blood and tissues.

The ratio of toluene to benzaldehyde was much higher in the PATM group, and this ratio is seen as a key sign of PATM.

Air quality in terms of petrochemicals is worse in urban areas, high traffic areas, industrial workspaces, poorly ventilated interiors, newly constructed or renovated spaces, automotive interiors, salons and beauty parlors, households using cleaning products containing petrochemicals, such as certain detergents, aerosol sprays, and solvents, spaces with indoor smoking and even some healthcare facilities.

Our previous study on breath VOC profiles in PATM, TMAU and MEBO (Alveolar Breath Test Study registered as NCT03451994) has unveiled intriguing insights into petrochemical metabolism, indicating that non-TMAU MEBO population may have difficulties with metabolizing environmental pollutants, while the Microbiome study (registered as NCT03582826) uncovered possible microbial sources of compounds that differentiate PATM, TMAU and MEBO from non-MEBO & non-PATM populations. Our findings align remarkably with Professor Sekine's work.

The synergy between these discoveries is shedding light on the underlying mechanisms and potential diagnostic markers. We will be publishing these complementary results soon, further contributing to the scientific community's knowledge of PATM, TMAU and MEBO.

Stay tuned for our upcoming publications, as we continue to unravel the mysteries of these conditions, working towards a future where this condition is better understood, diagnosed, and managed.

REFERENCES

Sekine Y, Oikawa D, Todaka M. Human skin gas profile of individuals with the people allergic to me phenomenon. Sci Rep. 2023 Jun 10;13(1):9471. doi: 10.1038/s41598-023-36615-1. PMID: 37301918; PMCID: PMC10257688.

Mobiluncus and Peptoniphilus

2023-07-08T07:16:00.006-07:00

Mobiluncus is one of bacteria reducing trimethylamine oxide to trimethylamine. It was also found to be associated with halitosis and bacterial vaginosis. We documented this bacterium in the gut and vaginal samples of several participants of our microbiome study. A new paper found Mobiluncus in umbilical dirt of the high odor score group.

Since odor scores did not show a normal distribution, samples were divided into two groups, one with an odor score ≥2.0 and one <2. Well-known resident bacteria of skin, such as Cutibacterium, Staphylococcus, and Corynebacterium, were not detected, whereas some anaerobic bacteria, including Mobiluncus (q-value=2.1E-33), Arcanobacterium (q-value=4.5E-22), and Peptoniphilus (q-value=4.3E-17), were highly abundant in umbilical dirt samples with high odor scores. The same genera were detected when samples were divided into two groups with an odor score ≥1.5 as the criterion.

By a predictive metagenome analysis using Picrust2, the authors identified genes that appeared to be specific to umbilical dirt with high odor scores. Metabolic pathways common to the extracted gene groups were analyzed by GSEA (Gene Set Enrichment Analysis). Anaerobic metabolic pathways, such as methane metabolism and glycolysis/gluconeogenesis, were more abundant in the high odor score group, and secondary metabolite production pathways, such as the biosynthesis of secondary metabolites and quorum sensing, were also identified.

While, Mobiluncus is associated with halitosis and bacterial vaginosis, Peptinophilus contributes to underarm odor by producing chemicals such as butyric acid. Acetobacter is one of species that could be counteracting the undesirable odors in this context.

REFERENCES

Yano T, Okajima T, Tsuchiya S, Tsujimura H. Microbiota in Umbilical Dirt and Its Relationship with Odor. Microbes Environ. 2023;38(3). doi: 10.1264/jsme2.ME23007. PMID: 37407492.

Valerie M, Milaine T, Aicha N, Roger A, Patrick MJ, Ibrahima D, Nehemie D, Laure N, Angeline B. Survey on Intravaginal Practices among Women of Reproductive Age at the Gynaeco-Obstetric and Pediatric Hospital of Yaounde: Association with Bacterial Vaginosis Caused by Gardnerella Vaginalis and Mobiluncus. International Journal Of Medical Science And Clinical Research Studies. 2023 Jan 30;3(1):121-6.

Zhang L, Hong Q, Yu C, Wang R, Li C, Liu S. Acetobacter sp. improves the undesirable odors of fermented noni (Morinda citrifolia L.) juice. Food Chemistry. 2023 Feb 1;401:134126.

Digital Forensics and Sensory Forecasting through VOC Analysis

2023-07-05T13:24:00.002-07:00

Everyone leaves a trace, whether it's a tangible object, invisible DNA, or even an odor.

In a recent study, a team of scientists achieved a remarkable 96% accuracy in determining human sex using a machine learning model guided by human expertise. Researchers collected hand odor samples from 60 individuals and analyzed them using Headspace-Solid Phase Microextraction-Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS). The results revealed distinct VOC signatures that allowed for the classification and prediction of gender. Various dimensional reduction techniques were employed to interpret the data, such as Partial Least Squares-Discriminant Analysis (PLS-DA), Orthogonal-Projections to Latent Structures Discriminant Analysis (OPLS-DA), and Linear Discriminant Analysis (LDA). The highest discrimination and classification of subject gender were observed with OPLS-DA and LDA as confidence level ellipses of both models were not seen to intersect.

In another study, a combination of deep learning, chemometrics, and sensory evaluation proved effective in distinguishing between various methods of roasting food. The researchers employed E-nose and E-tongue devices, quantitative descriptive analysis (QDA), HS-GC-IMS, and HS-SPME-GC–MS to differentiate lamb shashliks prepared through traditional charcoal grilling and four alternative methods. The results showed that these techniques effectively identified the characteristic flavors and volatile organic compounds (VOCs) associated with each roasting method. The clustering heat maps were generated using TBtools and Python was used to run SVM, RF, XGBoost, DNN 5-layer, CNN-SVM, and t-SNE. The CNN-SVM model outperformed other models in predicting VOC content and identifying the specific roasting methods.

REFERENCES

Chantrell J. G. Frazier ,Vidia A. Gokool ,Howard K. Holness,DeEtta K. Mills,Kenneth G. Furton. Multivariate regression modelling for gender prediction using volatile organic compounds from hand odor profiles via HS-SPME-GC-MS Published: July 5, 2023

https://doi.org/10.1371/journal.pone.0286452

Shen C, Cai Y, Ding M, Wu X, Cai G, Wang B, Gai S, Liu D. Predicting VOCs content and roasting methods of lamb shashliks using deep learning combined with chemometrics and sensory evaluation. Food Chem X. 2023 Jun 14;19:100755. doi: 10.1016/j.fochx.2023.100755. PMID: 37389322; PMCID: PMC10300318.

Exploring the Potential of Bioactive Textiles

2023-05-22T14:02:00.004-07:00

The advancements in textile technology led to fabrics that not only clothe us but also promote a healthier and safer lifestyle. From antimicrobial and antioxidant properties to anti-inflammatory and anti-odor capabilities, along with protection against ultraviolet (UV) radiation and repelling unwanted elements, these textiles are setting a new standard for comfort, protection, and style.

In an upcoming paper set to appear in the European Journal of Pharmaceutics and Biopharmaceutics (online ahead of print), the impact of bioactive textiles on human skin microbiota is extensively reviewed.

The paper highlights the growing recognition that textile materials have a profound impact on the microorganisms present on the skin, leading to issues such as biological degradation, loss of strength, elongation, discoloration, and unpleasant odors (see Van Herreweghen et al). The emergence of "maskne," a form of mechanical acne resulting from continuous textile-skin adherence, further underscores the significance of this impact, causing dysbiosis in the skin microbiota and the growth of specific disease-associated species.

Additionally, clothing textiles can act as carriers of microorganisms, posing risks of cross-infection, disease transmission, allergies, and malodors among individuals (reviewed in this paper). To address these challenges posed by microbial growth on textiles, the textile industry has made the search for new bioactive molecules with antimicrobial properties a top priority.

While functional textiles offer promising solutions, further research is needed to fully understand their environmental impact. To enhance the functionality of textiles and mitigate harm, the use of natural dyes derived from herbs, such as black cherry stems and hops flowers, is being explored. This approach not only improves functionality but also aligns with eco-friendly practices. Achieving the full potential of bioactive textiles requires interdisciplinary collaboration, bringing together expertise from various fields to develop safe and effective products that promote human health and safety.

REFERENCES

Suellen Ferro de Oliveira C, Kekhasharú Tavaria F. The impact of bioactive textiles on human skin microbiota. Eur J Pharm Biopharm. 2023 May 12:S0939-6411(23)00118-2. doi: 10.1016/j.ejpb.2023.05.004. Epub ahead of print. PMID: 37182552.

Van Herreweghen F, Amberg C, Marques R, Callewaert C. Biological and chemical processes that lead to textile malodour development. Microorganisms. 2020 Oct 31;8(11):1709.

Gulati R, Sharma S, Sharma RK. Antimicrobial textile: recent developments and functional perspective. Polymer Bulletin. 2022 Aug;79(8):14346-14364, DOI: 10.1080/15440478.2022.2064391

Lactobacillus, Bifidobacterium and other emerging probiotics

2023-03-23T18:02:00.009-07:00

In the past few decades, Lactobacillus and Bifidobacterium genera were the main bacteria to be used as probiotics. One of the reasons for such attention was that these bacteria have the ability to thrive aerobically and are simple to package for sale. Cass Nelson-Dooley and Tony Hoffman of Metametrix (acquired by Genova Diagnostics in 2012) talked about these probiotics in MEBO interviews in 2009, emphasizing that high levels of Lactobacillus could be bad in some cases. Diets rich in simple carbs, poor absorption and small intestinal pockets can feed and trap excess Lactobacillus. Adding probiotics Bifidobacteria or Saccharomyces boulardii and prebiotic fiber to the diet could, in their opinion, help the MEBO population. D-lactate was one of the tests they offered that measured the level of this byproduct of bacterial fermentation, indicating an overgrowth of bacteria in the small intestine. According to our early clinical studies, D-lactate, however, was elevated in less than 20% of MEBO and PATM populations.

Even though Lactobacillus is only a minor member of the human colonic microbiota, the proportions of those bacteria and particular strains are frequently either positively or negatively correlated with human disease and chronic conditions. Although it generally is not considered a pathogen, it can cause disease in compromised hosts, including bacterial endocarditis, pleuropulmonary infections, gastrointestinal abscesses, urinary tract infection, conjunctivitis, dental caries, and endometritis. Lactobacillus bacteremia, presumably secondary to bacterial translocation from the gastrointestinal tract, has been reported in a patient with severe intestinal inflammation caused by ulcerative colitis. A decrease in genus Faecalibacterium and increase in Lactobacillaceae has been previously reported in patients with constipation (Lactiplantibacillus plantarum P9 supplementation, on the other hand, helped to increase frequency of bowel movements, while L11 improved gut health and odor in cats). Compared to healthy individuals, pediatric and adult Crohn's disease (CD) patients had an increased relative abundance of Lactobacillus species. In both cases, Lactobacillus enrichment coincided with depletion of F. prausnitzii - that could represent a good candidate as next-generation probiotic. Another study found that Weissella cibaria ZWC030 can inhibit skatole.

The percentages of Bifidobacterium and the Lactobacillus group presented a decreasing trend in patients with quiescent ulcerative colitis (UC) compared to active UC, although no significant differences were observed. Excessive amounts of Bifidobacteria can have negative effects on the body, such as in the case of Bifidobacterium breve bacteremia caused by excessive probiotic supplementation in infants with gastrointestinal conditions. On the other hand, Lactobacillus, Bifidobacterium and F. prausnitzii are depleted in IBS patients, resulting in lower SCFA concentrations (short-chain fatty acids, which are organic acids produced by gut bacteria during fermentation of indigestible foods) compared with healthy individuals. Maternal prenatal stress could also cause lower levels of Lactobacillus and Bifidobacterium and keep them low even later in life. With lower levels of Bifidobacterium, celiac patients have an imbalance in the intestinal microbiota, regardless of pH, even while on a gluten-free diet. Hormone treatment affects Bifidobacterium longum's ability to produce acids: progesterone reduces lactic acid and acetic acid production, while estradiol and thyroxine increase levels of both lactic acid and acetic acid (ethinyl estradiol) or lactic acid and butyric acid (thyroxine hormone).

Data from our microbiome study (NCT03582826: Microbial Basis of Systemic Malodor and "People Allergic To Me" Conditions - ClinicalTrials.gov) show that while there was a general trend of increasing levels of Bifidobacteria and Lactobacillus in individuals who achieve remission, less than 10% of participants needed to boost levels of both species to improve their condition. In line with previous knowledge, in MEBO/PATM population, Bifidobacteria (one of the first microbes to colonize the human gastrointestinal tract) was more common in younger individuals. About one third of the participants experienced lesser symptoms when increasing levels of their gut Bifidobacteria, another third benefited from more Lactobacillus and the remaining third felt better when increasing levels of Faecalibacterium prausnitzii (a butyrate-producing anaerobe typically associated with good health). Changes in the levels of these bacteria corresponding to recovering are overlayed on Figure 5 from our paper published in JMIR dermatology. It was illustrating changes in microbial diversity vs abundances of selected bacterial species associated with odor (CSS) for 12 female (F1-F12) and 10 male (M1-M19) participants who self-reported both flare-ups (beginning of the arrow) and improvements (end of the arrow). We added text boxes showing whether the levels of F. prausnitzii (F), Bifidobacterium (B) and Lactobacillus (L) are increasing (🡹) , decreasing (🡻) or fluctuating (🡺) as symptoms resolve. It is obvious that individuals with the highest bacterial diversity don't benefit from increasing levels of probiotic diversity, while those with low diversity levels do need more probiotic microbes in their system. The figure demonstrates the complexity of these bacterial perturbations and emphasizes the need to consider more than just three species when predicting which treatment will work best for reducing MEBO and PATM symptoms.

As we mentioned in the previous blog post, Lactobacillus is the main genera responsible for odors of the uncooked food waste and off-flavor pit mud. Some strains of Lactobacillus produce lactic acid, which can contribute to a more acidic environment in the gut. This can be beneficial for some people, but for others it can exacerbate odor issues. Bifidobacteria could also produce organic acids such as acetic acid and lactic acid in addition to short-chain fatty acids (SCFAs) like butyrate, which can have anti-inflammatory effects and promote gut health, but some people may find it unpleasantly smelling. F. prausnitzii produces a range of metabolites including one of the worst smelling compounds Putrescine. F. prausnitzii plays important role in balancing immunity. Its butyrate production has been correlated to the capacity to induce IL-10, an anti-inflammatory cytokine, in peripheral blood mononuclear cells (PBMC) but not to the ability to block IL-8 secretion in TNF-α-stimulated HT-29 cells. In COVID-19, Faecalibacterium prausnitzii has been inversely correlated with disease severity.

Research has shown that the gut microbiome is far more complex than previously thought, with hundreds of bacterial species interacting in a delicate balance. Therefore, focusing solely on Lactobacillus and Bifidobacterium, or any other bacterium, may not be enough to promote a healthy gut microbiome for everyone. Besides, different strains of bacteria within the same species can have different effects on the body.

After more than a century of research, the following species are identified as the primary probiotic species of Lactobacillus species: L.acidophilus, L.casei, L.fermentum, L.gasseri, L.johnsonii, L.paracasei, L. plantarum, L. rhamnosus, and L. salivarius. For Bifidobacteria these are: B.adolescentis, B.animalis, B.bifidum, B.breve, and B.longum. We are learning more about strains of these species. Novel probiotic strain Bifidobacterium bifidum CECT 7366 is active against the pathogenic bacterium Helicobacter pylori - and so are variations of Saccharomyces Boulardii and Lactobacilli johnsonii. Another strain L. plantarum 299v can directly interfere with E. coli colonization and improve the immunological status of the intestinal mucosa although these results have not yet been confirmed in humans. Lactobacillus GR-1 and B-54 or RC-14 strains in the vagina has been shown to reduce the risk of urinary tract infections. Mileti et al. found that Lactobacillus paracasei displayed a delay in the development of colitis and a decreased severity of disease but that L. plantarum and L. rhamnosus GG exacerbated the development of dextran sodium sulfate (DSS)-induced colitis.

L. rhamnosus supplementation contributes to higher intestinal absorption of free choline and elevated production of methylamines including TMA, whereas L. paracasei consumption may result in increasing bacterial consumption of choline for cholesterol assimilation and phospholipid metabolism rather than for methylamine metabolism.

Bifidobacterium supplemented with various fiber additives can prevent the growth of Clostridium difficile, while Lactobacillus salivarius protects the broiler chicks from Salmonella infections. Several strains of other species promising as probiotics are from Roseburia spp., Akkermansia spp., and Faecalibacterium spp. Probiotic potential risk score (PPRS) allowed to classify 84 Faecalibacterium prausnitzii strains into low-, medium-, and high-risk groups. 15 strains identified as low-risk strains are prioritized for clinical application.

Unfortunately, the extreme oxygen sensitivity of F. prausnitzii imposes practical challenges to the production, transportation, storage, and manufacturing of probiotic products to be evaluated in a clinical setting. Instead, we have to turn to prebiotics - a type of dietary fiber - in our food . F. prausnitzii's growth is promoted by inulin, inositol (vitamin B8) and fructo-oligosaccharides, chicory roots, wheat, onion, banana, garlic, and leek, wheat, rye, rice, barley, oat, and sorghum, and gold kiwifruit.

Gut microbiota can be also influenced by phytochemicals. In one study, black raspberry (BR) reduced the serum levels of trimethylamine-N-oxide and cholesterol in rats fed excessive choline with a high-fat diet (HFC). The authors hypothesized that since gut microbiota plays a crucial role in the production of trimethylamine and microbial metabolites, BR could influence gut microbial composition. Their study examined microbiomes and metabolomes of rats and showed that the BR supplementation enriched Bifidobacterium and reduced Clostridium cluster XIVa.

While we have made significant progress in understanding the role of probiotics and prebiotics in supporting our gut health, it's important to recognize that there is still a great deal that we don't know. It's becoming increasingly clear that a personalized approach to prebiotic and probiotic use may be necessary to achieve optimal health outcomes. This approach involves paying attention to how different foods make you feel and adjusting your diet accordingly, while eating a diverse and balanced diet that incorporates a variety of whole foods and phytochemicals, staying hydrated, getting enough sleep and exercise, and managing stress levels. Focusing on overall health and well-being will help to support the body's natural ability to maintain a healthy microbiome and avoid dysbiosis-related health issues.

REFERENCES

Din AU, Hassan A, Zhu Y, Yin T, Gregersen H, Wang G. Amelioration of TMAO through probiotics and its potential role in atherosclerosis. Applied Microbiology and Biotechnology. 2019 Dec;103:9217-28.

Pacifico L, Osborn JF, Bonci E, Romaggioli S, Baldini R, Chiesa C. Probiotics for the treatment of Helicobacter pylori infection in children. World J Gastroenterol 2014; 20(3): 673-683 [PMID: 24574741 DOI: 10.3748/wjg.v20.i3.673]

Lim T, Lee K, Kim RH, Ryu J, Cha KH, Park SY, Koo SY, Hwang KT. Effects of black raspberry extract on gut microbiota, microbial metabolites, and expressions of the genes involved in cholesterol and bile acid metabolisms in rats fed excessive choline with a high-fat diet. Food Sci Biotechnol. 2023 Feb 13;32(4):577-587. doi: 10.1007/s10068-023-01267-4. PMID: 36911337; PMCID: PMC9992478.

Heeney DD, Gareau MG, Marco ML. Intestinal Lactobacillus in health and disease, a driver or just along for the ride?. Current opinion in biotechnology. 2018 Feb 1;49:140-7.

Martín R, Miquel S, Benevides L, Bridonneau C, Robert V, Hudault S, Chain F, Berteau O, Azevedo V, Chatel JM, Sokol H. Functional characterization of novel Faecalibacterium prausnitzii strains isolated from healthy volunteers: a step forward in the use of F. prausnitzii as a next-generation probiotic. Frontiers in microbiology. 2017 Jun 30;8:1226.

Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS, Cook JR, Nordvig AS, Shalev D, Sehrawat TS, Ahluwalia N. Post-acute COVID-19 syndrome. Nature medicine. 2021 Apr;27(4):601-15.

Bai Z, Zhang N, Jin Y, Chen L, Mao Y, Sun L, Fang F, Liu Y, Han M, Li G. Comprehensive analysis of 84 Faecalibacterium prausnitzii strains uncovers their genetic diversity, functional characteristics, and potential risks. Frontiers in Cellular and Infection Microbiology. 2023 Jan 4;12:1924.

Gabashvili I.S. Cutaneous Bacteria in the Gut Microbiome as Biomarkers of Systemic Malodor and People Are Allergic to Me (PATM) Conditions: Insights From a Virtually Conducted Clinical Trial. JMIR Dermatol 2020;3(1):e10508 URL: https://derma.jmir.org/2020/1/e10508 DOI: 10.2196/10508

Rašić, J.L., Vujičić, I.F., Škrinjar, M. et al. Assimilation of cholesterol by some cultures of lactic acid bacteria and bifidobacteria. Biotechnol Lett 14, 39–44 (1992). https://doi.org/10.1007/BF01030911

Food, Hormones and Odor Pollution

2023-01-25T13:46:00.016-08:00

While there is not enough research on human odors, there are plenty of studies that can be related to this topic. Scientific papers published in January are about goats, fish, fermented food and biological waste.

It is worth examining some of the latest findings and how they may be translated into take-home messages for humans.

1. Intermittent fasting could improve body odor.

At least for fish. The study aimed to investigate the response of intestinal microbiota during 3 weeks’ starvation of largemouth bass (Micropterus salmoides), found that food deprivation helped to improve the odor of an economically important freshwater fish by reducing earthy-musty off-flavor compounds such as geosmin and 2-methylisoborneol. The study revealed that certain actinobacteria such as Microbacterium and Nocardioides were able to grow better than Mycoplasma, Pseudomonas, Acinetobacter, and Microbacterium when the fish were in a fasted state. This suggests that intermittent fasting may help to improve body odor by promoting the growth of beneficial bacteria and reducing the growth of odor-causing bacteria. However, more research is needed to confirm these findings in human studies. Besides, our own data show that people smell worse when starving themselves and it is a good idea to not go overboard.

2. Adding fiber to diet and reducing stress levels can improve body odor.

Korean native black goats (KNBG) are able to adapt to a wide variety of climatic conditions and foraging preferences. Twenty-four KNBG (48.6 ± 1.4 kg) were randomly allocated to one of four treatments featuring different dietary forage (high in fiber) to concentrate ratio (high forage [HF, 80:20] and low forage [LF, 20:80]), and a castration treatment (castration [CA] vs. non-castration [NCA] - aka higher levels of sex hormones, stress hormones). The animals were maintained on a free-choice feed and water regimen.

The intensity of a strong “goaty” flavor was remarkably enhanced when non-castrated KNBG were fed with the low forage diet. Better smelling goats had more hydrocarbons and ketones while worse smelling ones were higher in aliphatic aldehydes, possibly owing to the activity of testosterone, androsterone, and skatole. For volatile compounds, dichloromethane (chloroform-like odor) and m-xylene (plastic odor) were reported to be linked with the “strong lamb odor” influenced by dietary selection.

10% fermented mixed feed supplementation (compared to 5% or 0%) helped to improve flavor of pork by increasing the contents of total aldehydes, (E,E)-2,4-nonadienal, dodecanal, nonanal and 2-decenal, along with inosine monophosphate.

A healthy gut microbiome may positively influence sex hormones by regulating the appetite and reducing insulin resistance. Acute psychosocial stress, on the other hand, causes unhealthy fluctuations in sex hormone levels.

Here are a few tables compiled from the goat diet/hormones article:

Microbe Genus	Compounds positively correlated	Compounds negatively correlated.
Flexilinea	C16:0 (Palmitic acid, oily smell)	C18:2n6 (Methyl linoleate, oily odor), C18:3n3 (Linoleic acid, oily, low odor), PUFA
Ihubacter	C16:0 (Palmitic acid, oily smell)	C18:2n6, C18:3n3 (Linoleic acid), PUFA
Ruminococcus	-	C16:0 (Palmitic acid, oily smell)
Christensenella	C18:0 (Stearic acid), PUFA	C16:1n7 (Palmitoleic Acid, Cardioprotective - smells like Old Books)
Lachnoclostridium	C18:1n9 Oleic acid)	C18:2n6, C18:3n3 (Linoleic acid),, PUFA
Treponema	-	C18:0 (Stearic acid), C18:3n3 (Linoleic acid), C20:4n6 (Arachidonic acid: from marine, at low concentrations, to intense orange-citrus and animal-like odor)
Succiniclasticum	C18:1n7 (Vaccenic acid), C18:3n3 (Linoleic acid)	-
Desulfovibrio	C18:1n7 (Vaccenic acid)	-
Blautia	-	C18:2n6 (Linolelaidic acid)
Rhabdanaerobium	-	C18:3n3 (Linoleic acid)
Gracilibacter	-	C18:3n3 (Linoleic acid)
Butyrivibrio	-	C18:3n3 (Linoleic acid)
Paraprevotella	C20:4n6, C22:4n6	-
Intestinimonas	C22:4n6	-

This table summarizes the relationship between meat fatty- composition and rumen bacteria at the genus level.

Higher levels of carbohydrates may promote the persistence and flavor formation of Z. rouxii (Zygosaccharomyces, a genus of yeasts in the family Saccharomycetaceae) in the moromi soy sauce, and it changes its aroma profile. Not sure if it is to the better or worse.

3. Acinetobacter is associated with fish odor and the odor of biowaste. It is also associated with odor in MEBO and PATM populations - this is one of not yet published results of our microbiome study (in addition to skin bacteria)

A study to be published in print in the February issue of "Science of The Total Environment", examined odor profiles of cooked and uncooked food waste.

Odor pollution often occurs in the initial decomposition stage of municipal biowaste, including throwing/collection and transportation. However, this aspect of odor impact from municipal biowaste has not been well studied. In Nie and colleagues' experiments, a practical dustbin (120 L) equipped with flux chamber and filled with three types of municipal biowaste was used to simulate garbage storage conditions. The result indicated that the emission rate of odor pollutants for uncooked food waste (UFW) represented a nearly linear growth trend, reaching the maximum (3963 ± 149 μg kg−1 DM h−1) at 72 h. Cooked food waste (CFW) increased rapidly from 8 h to 24 h, and then remain fluctuated, reached the maximum (2026 ± 77 μg kg−1 DM h−1) at 72 h. Comparatively, household kitchen waste (HKW) reached the maximum emission rate (10,396 ± 363 μg kg−1 DM h−1) at 16 h. Sulfide and aldehydes ketones were identified as dominant odor contributor to UFW and CFW, respectively. While aldehydes ketones and sulfides were both dominant odor contributor to HKW. Moreover, the microbial diversity analysis suggests that Acinetobacter was the dominant genus in UFW, and Lactobacillus was the dominant genus in CFW and HKW. In addition, it was evident that each odorous pollutant was significantly associated with two or more bacterial genera, and most bacterial genera such as Acinetobacter, were also significantly associated with multiple odorous pollutants. The variation of odorants composition kept consistent with microbial composition. The present study could provide essential evidence for a comprehensive understanding of odorant generation in the initial decomposition stage of municipal biowaste. It could contribute to setting out strategies for odor control and abatement in municipal biowaste management systems.

The highest emission was observed in household kitchen waste with alcohol esters.

The highest total odor activity values were observed in uncooked food waste.

Lactobacillus was the dominant genus in household kitchen waste and cooked food waste.

Acinetobacter was the dominant genus in uncooked food waste.

The variation of odorants composition kept consistent with microbial composition.

REFERENCES

Lee J, Kim HJ, Lee SS, Kim KW, Kim DK, Lee SH, Lee ED, Choi BH, Barido FH, Jang A. Effects of diet and castration on fatty acid composition and volatile compounds in the meat of Korean native black goats. Anim Biosci. 2023 Jan 11. doi: 10.5713/ab.22.0378. Epub ahead of print. PMID: 36634653. download pdf

Zou S, Ni M, Liu M, Xu Q, Zhou D, Gu Z, Yuan J. Starvation alters gut microbiome and mitigates off-flavors in largemouth bass (Micropterus salmoides). Folia Microbiologica. 2023 Jan 13:1-2.

Lülf RH, Selg-Mann K, Hoffmann T, Zheng T, Schirmer M, Ehrmann MA. Carbohydrate Sources Influence the Microbiota and Flavour Profile of a Lupine-Based Moromi Fermentation. Foods. 2023 Jan 2;12(1):197. doi: 10.3390/foods12010197. PMID: 36613413; PMCID: PMC9818829.

Nie E, Wang W, Duan H, Zhang H, He P, Lü F. Emission of odor pollutants and variation in microbial community during the initial decomposition stage of municipal biowaste. Sci Total Environ. 2023 Feb 25;861:160612. doi: 10.1016/j.scitotenv.2022.160612. Epub 2022 Nov 29. PMID: 36455726.

Shi Q, Tang X, Liu BQ, Liu WH, Li H, Luo YY. Correlation between microbial communities and key odourants in fermented capsicum inoculated with Pediococcus pentosaceus and Cyberlindnera rhodanensis. J Sci Food Agric. 2023 Feb;103(3):1139-1151. doi: 10.1002/jsfa.12321. Epub 2022 Nov 24. PMID: 36349455.

Search Odors (cdc.gov) - database of toxic chemicals

OdorDB: Home (yale.edu)

Current Trends in Deodorization

2022-12-20T14:06:00.009-08:00

In the Victorian era, people would wash off with a sponge soaked in cool water and vinegar, use sweat-absorbing pads in armpit areas and overwhelm unpleasant smells with perfume. The most popular scent was ambergris known for its marine, sweat and earthy scent with a fecal note (if not properly aged). Since energy was obtained from burning of fuels, large amounts of sulfur were always present in the air, covering odors of animal and human waste released into river and streams.

Engineers eventually designed centralized closed water sewage treatment systems and modern plumbing, enabling rigorous personal hygiene. But in the early 1900s, fear-based marketing convinced people that they smelled bad, and this turned niche deodorant trades into a $22 billion industry. Odorono (from "Odor? Oh No!") was one of the first antiperspirants at the forefront of this transformation.

The use of antiperspirant deodorants has been declining in recent years due to their potential effect on health and environment, and the availability of more natural and organic alternatives. COVID-19 pandemics has also negatively affected the deodorant market. As a result, the demand for deodorization has decreased during these times. But innovation continues.

Across North America, the deodorants market witnessed growth of few brands creating antiperspirants intended for alternative body parts, such as hands, face, and feet. For example, Gamer Grip Hand Antiperspirant, designed for athletes to improve their grip, has a lasting fragrance for 4 to 6 hours. Neat 3B Face Saver is an antiperspirant gel for the face that can be applied before makeup. Carpe No-Sweat Face is a natural, sweat absorbing gelled lotion created with sweat absorbing ingredients like jojoba esters, vitamin B3, silica microspheres, aloe vera, and colloidal oatmeal.

In the early 2000s, new types of deodorants appeared on the market. Deo Perfume Candy, Swallowable Parfum, and Otoko Kaoru were designed as edibles, and the fragrance was supposed to be released from the user's mouth and nose. However, these products were eventually discontinued due to safety concerns, as well as their lack of popularity.

Beginning in the mid-2000s, many clothing companies started incorporating silver nanoparticles into their products including nano-engineered anti-odor textiles. While the technology was initially developed for use in the medical industry (antimicrobial wound dressings), nano-porous materials in clothing presented another way to manage body odor. These materials offered the potential to make traditional deodorants old-fashioned or even obsolete.

Ag nanoparticles, for example, are effective at slowing the growth of bacteria that cause body odor and itchiness. Nano-silver socks help in preventing bacterial and fungal growth. Haojey creates textiles comprising a TiO2 particle core to provide UV resistance, silver nanoparticles for antibacterial textiles, and nanobamboo for odor adsorption. Cotton treated with pomegranate and galnut extract showed excellent deodorizing performance against trimethylamine. Odor-free medical masks are fabricated using Polyvinyl Butyral and Eucalyptus Anti Odor Agent. Aloe Vera and Polyvinyl Alcohol (AV/PVA) electrospun nanofibers show excellent results suppressing growth of S. aureus bacteria (by ~25%) although not E. coli. A team from UC Berkeley introduced a way to reduce underarm sweating and odor by using a cross-linked microporous copolymer containing methacrylate and acrylate units.

Unfortunately, many of nano-infused textile products are investigated as skin irritants. Besides, considerable amounts of Ag nanoparticles were found to be released on washing Ag nanoparticle integrated fabrics, which is highly toxic to aquatic life.

Another trend in the world of skincare that started in the late 2000s was topically applied probiotics.

Although the idea is not new, as research into the human microbiome began to uncover the role that probiotics could play in improving health, the use of probiotics, prebiotics and postbiotics to help combat odor-causing bacteria began to gain traction. Oral deodorizers with probiotics are already commonly found in the market in the form of chewing tablets, lozenges, and capsules. Topical probiotic formulations could exert anti-inflammatory effects by stimulating regulatory T-cells and release of anti-inflammatory cytokines such as IL-10, within the immune system, competing with odor-causing microbes for nutrients, and aggregating and displacing them. When applied to the skin, Lactobacilli, for example, exhibits antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, and Cutibacterium (formerly Propionibacterium) acnes. Topical microbiome transplantation (Roseomonas mucosa lysate cultured from healthy volunteers) is believed to improve atopic dermatitis by restoring epithelial barrier function and innate/adaptive immune balance as well as via inhibition of S. aureus growth. Nitrosomonas eutropha improves appearance of skin. Transplantation of microbiome enriched in S. epidermidis helped to reduce axillary malodor in siblings or other matching individuals. Bacteria responsible for odor emitted from the skin is known and is common for individuals suffering from a variety of odor disorders, including those with genetic variations in ABCC11, FMO3 and those with idiopathic malodor. The presence of these bacteria in the gut microbiome correlates with the intensity of malodor. Balancing composition of gut microbes will definitely help to improve the odor but may take a long time and require tailor-made diets. And it is not clear if "suicide substrate inhibitors" such as iodomethylcholine are sufficiently safe to use.

More than a dozen topical probiotic species have been found to have a unique spectrum of characteristics, including keratin adhesion, inhibitory action, organic acid production, and inhibition of biofilm formation, skin whitening, moisturizing, anti-aging, anti-wrinkle and removing body odor. A new bilayer vaginal tablet of Lactococcus lactis has been designed for the treatment of vaginal bacterial infections and could also help to combat unpleasant odors. And so could Nitrosomonas eutropha, although so far it was only proven to help with acne. Genetically modified bacteria are also being investigated as topical therapeutics. Candidate genes are Fillaggrin, LEKTI, IL-10, genes encoding growth factors and hormones. Studies of safety and efficiency are still, however, in very early stages. The application of high amounts of bacteria, could, for example, lead to a skin immune reaction with irritation and side effects as a result. It could also lead to infection.

The skin microbiome is relatively stable and quickly restores after washing and skincare product application, even if they contain antimicrobials. The reason is, skin microbiome is actually derived from within the skin, the deeper stratum corneum layers, skin hair follicles and is connected to the gut microbiome. Skin microbiome transplantation methods are currently being investigated and showed some promising results although many challenges remain that need to be overcome.

Probiotic-infused products and skin transplants are gaining popularity due to their ability to promote healthy bacteria growth on the skin, which can, for example, help reduce body odor. However, there is still a lack of strong scientific evidence of effectiveness and a lack of thorough understanding of side effects. Probiotics are living microorganisms, which means that they are sensitive to environmental conditions and can be difficult to work with. This can make it challenging to incorporate probiotics into skincare products in a way that preserves their effectiveness and stability. Finally, there are regulatory issues to consider when it comes to introducing new probiotic-based skincare products to the market. In order to be sold as a cosmetic product, a skincare product must be safe and effective, and the manufacturer must provide evidence to support these claims. This process can be time-consuming and costly and may discourage some companies from investing in the development of new probiotic-based skincare products.

Overall, while there is a growing interest in the potential benefits of probiotics, prebiotics and postbiotics for the skin, the development of new probiotic-infused skincare products is likely to continue to be slow and incremental as researchers and manufacturers work to understand more about how probiotics work and how they can be effectively incorporated into skincare products.

It is likely that skincare products developed in the future will be tailored to specific genetic profiles, as researchers continue to learn more about the role that genetics plays in skin health and the skincare concerns that people may have.

One example is a urea-containing moisturizer that could be effective for people with a certain genetic variation in the filaggrin gene, Transient erythema (reddening of skin) is a potential side effect. A number of genes (such as MC1R, ASIP and BNC2) are related to skin conditions including sun sensitivity, skin moisturizing function, oxidative stress, stretch marks, and skin inflammation and are being investigated in personalized skincare R&D.

Gene therapy and enzyme replacement therapies have achieved some notable successes in recent years. For instance, the US Food and Drug Administration (FDA) approved Luxturna for a rare form of inherited blindness, and Kymriah using genetically modified T cells to attack cancer cells, in 2017. However, the costs of research and development and the risk of side effects are extremely high.

As a result, it can be difficult to obtain funding for non-fatal conditions like TMAU (trimethylaminuria). Trinzyme, a company focused on enzyme replacement therapies, was founded in 2011 with the goal of developing treatments for TMAU. While the company was able to secure initial funding, it has not yet been able to deliver on its promise of a treatment for this condition. Despite these challenges, the potential for gene therapy and enzyme replacement therapies to revolutionize the way we treat and prevent diseases remains significant, and research and development in these fields continues to advance.

In 2022, several companies started testing their deodorizing cosmetic products intended to block smelly chemical trimethylamine, emitted from the skin if the liver cannot completely break down this product of essential nutrients. Spain-based perfume manufacturer Eurofragance has recently teamed up with a Barcelona Children Hospital on a project to neutralize the strong odor of those who suffer from trimethylaminuria (caused by genetic mutations that affect the FMO3 function of the liver). The hospital's program initially focused on pediatric subjects with primary carnitine deficiency, manifesting as metabolic encephalopathy, lipid storage myopathy, or cardiomyopathy. Since the patients are not able to process long-chain fatty acids to convert them into energy, the accumulation of toxic fatty acyl derivatives impedes gluconeogenesis and urea cycle function which, in turn, causes hypoketotic hypoglycemia, transaminase elevations, and hyperammonemia - hence fishy odor. Eurofragance solution has citrus notes blocking the fish odor receptors in the nose. This way the fishy odor does not disappear, but it is not perceived. Eurofragance designed body cream lotion with 1% fragrance, an eau de toilette with 5% fragrance and a body serum with 2% fragrance. Other businesses designing their own solutions were Nannic "Skin care by science", and stealth-mode teams from British and US companies.

While there is still a lot more research to be done, the development of these new deodorizing cosmetic products has provided hope for those who struggle with trimethylaminuria and similar conditions.

REFERENCES

Callewaert C, Knödlseder N, Karoglan A, Güell M, Paetzold B. Skin microbiome transplantation and manipulation: Current state of the art. Computational and Structural Biotechnology Journal. 2021 Jan 1;19:624-31.

Gabashvili IS. Cutaneous Bacteria in the Gut Microbiome as Biomarkers of Systemic Malodor and People Are Allergic to Me (PATM) Conditions: Insights From a Virtually Conducted Clinical Trial JMIR Dermatol 2020;3(1):e10508 URL: https://derma.jmir.org/2020/1/e10508 DOI: 10.2196/10508

Gabashvili IS. Identifying subtypes of a stigmatized medical condition. medRxiv. 2019 Jan 1:19005223.

Habeebuddin M, Karnati RK, Shiroorkar PN, Nagaraja S, Asdaq SM, Khalid Anwer M, Fattepur S. Topical Probiotics: More Than a Skin Deep. Pharmaceutics. 2022 Mar 3;14(3):557.

Lee GR, Maarouf M, Hendricks AJ, Lee DE, Shi VY. Topical probiotics: the unknowns behind their rising popularity. Dermatology Online Journal. 2019;25(5).

Lee YH, Lee SG, Hwang EK, Baek YM, Cho S, Kim JS, Kim HD. Deodorizing performance and antibacterial properties of fabric treated with pomegranate and gallnut extracts compared with properties of commercial deodorizing and antibacterial agents. Textile Science and Engineering. 2016;53(1):45-54.

Myles IA, Earland NJ, Anderson ED, Moore IN, Kieh MD, Williams KW, Saleem A, Fontecilla NM, Welch PA, Darnell DA, Barnhart LA. First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis. JCI insight. 2018 May 5;3(9).

Qadir MB, Jalalah M, Shoukat MU, Ahmad A, Khaliq Z, Nazir A, Anjum MN, Rahman A, Khan MQ, Tahir R, Faisal M. Nonwoven/Nanomembrane Composite Functional Sweat Pads. Membranes. 2022 Dec 5;12(12):1230.

Yang J. Personalized Skin Care Service Based on Genomics. InInternational Conference on Health Information Science 2021 Oct 25 (pp. 104-111). Springer, Cham.

Olfactory Signatures and COVID-19

2022-11-17T18:20:00.013-08:00

Olfactory disorders have a significant impact on human lives - be it a lost/distorted sense of smell or unpleasant odors affecting the sense of smell of others.

Odortypes can be influenced by human leukocyte antigen (HLA) genes of the major histocompatibility complex (MHC), genes associated with stronger response to COVID-19 vaccine as well as the severity of this disease. HLA may also be related to people's perception of the odor of other people.

Of course, these are not the only variables involved, and there are more potentially overlapping risk factors for olfaction, metabolic body odor (MEBO), including trimethylaminuria (TMAU), and COVID-19: FMO3, SELENBP1, HspA, UGT2A1/UGT2A2, etc.

A new peer-reviewed paper reporting results of a decentralized observational study (NCT04832932) compared MEBO participants to general populations in respect to their response to COVID-19 vaccines and SARS-Co-V2 infections.

Body odor flareups were observed in about 10% of malodor sufferers after vaccination, as preliminarily reported. This number was similar to flareups of other chronic symptoms in groups of participants with gastrointestinal and autoimmune disorders.

Long-term worsening of body odor was observed by other researchers after COVID-19 vaccination in about ~1% of studied populations. Dry mouth leading to halitosis was 10 times more prevalent compared to flu vaccines. MEBO participants reported stronger reactions than general population pointing to genetic and microbiome influences beyond FMO3.

A better understanding of systemic malodor conditions could offer leads for targeted therapies. Findings on genetic and microbiome overlaps between COVID-19 and MEBO could pave the way for precision medicine to address the unmet needs of odor sufferers.

REFERENCE

Gabashvili IS. The Incidence and Effect of Adverse Events Due to COVID-19 Vaccines on Breakthrough Infections: Decentralized Observational Study With Underrepresented Groups. JMIR Formative Research. 2022 Nov;6(11):e41914. DOI: 10.2196/41914. PMID: 36309347; PMCID: PMC9640199.

On Cabbage and Selenium Binding Protein 1

2022-04-20T16:36:00.046-07:00

Mutations in the gene encoding Selenium Binding Protein (SELENBP1) on chromosome 1q21 were found in multiple individuals with extra-oral halitosis. These individuals had increased levels of methanethiol and dimethylsulfide in their breath perceived as unpleasantly cabbage-smelling. It was reported to worsen after drinking beer.

The mutations responsible include rs1553204817 (OMIM: 604188.0001: c.1039G>T); rs758495626 (c.673G>T (p.Gly225Trp)), rs1357490520 (c.481+1G>A disrupting splice site), and rs1553204840 (c.985C>T)

SELENBP1 was identified as a methanethiol oxidase (MTO), catalyzing the conversion of methanethiol (H3C-SH) to hydrogen sulfide (H2S), hydrogen peroxide (H2O2) and formaldehyde (HCHO). If this enzyme is not properly functional, the body will be releasing more Methanethiol - a volatile and toxic gas with the characteristic smell of rotten cabbage. We get this compound from food - not only the cancer-fighting cabbage family, including radishes, but also orange juice, pineapple, strawberries, asparagus, wheat bread, gruyere cheese, coffee, roasted filberts and even cooked rice. Water, cherries, apples, whole milk, spinach and citrusy fruits could counteract the odor in some individuals.

Selenium binding protein1 (SELENBP1) has been also associated with a rare disease hypermethioninemia (sometimes accompanied by learning disabilities and neurological problems), several cancers and schizophrenia (downregulated at its onset and upregulated at later stages); hypertension and ischemic heart conditions. Dysregulation of SELENBP1 is common to Zika virus (ZIKV) and dengue infections, and Guillain-Barré syndrome. It was also found to COVID-19.

REFERENCES

Pol A, Renkema GH, Tangerman A, Winkel EG, Engelke UF, De Brouwer AP, Lloyd KC, Araiza RS, Van Den Heuvel L, Omran H, Olbrich H. Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis. Nature genetics. 2018 Jan;50(1):120-9.

Philipp TM, Will A, Richter H, Winterhalter PR, Pohnert G, Steinbrenner H, Klotz LO. A coupled enzyme assay for detection of selenium-binding protein 1 (SELENBP1) methanethiol oxidase (MTO) activity in mature enterocytes. Redox Biology. 2021 Jul 1;43:101972.

Lin X, Lin Z, Zhao X, Liu Z, Xu C, Yu B, Gao P, Wang Z, Ge J, Shen Y, Li L. Serum SELENBP1 and VCL Are Effective Biomarkers for Clinical and Forensic Diagnosis of Coronary Artery Spasm. International Journal of Molecular Sciences. 2022 Oct 31;23(21):13266.

Chau EJ, Mostaid MS, Cropley V, McGorry P, Pantelis C, Bousman CA, Everall IP. Downregulation of plasma SELENBP1 protein in patients with recent-onset schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2018 Jul 13;85:1-6.

Zhang X, Hong R, Bei L, Hu Z, Yang X, Song T, Chen L, Meng H, Niu G, Ke C. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition. Open Medicine. 2022 Jan 1;17(1):1390-404.

Moni MA, Lio’ P. Genetic profiling and comorbidities of zika infection. The Journal of infectious diseases. 2017 Sep 15;216(6):703-12.

de Melo CV, Bhuiyan MA, Gatua WN, Kanyerezi S, Uzairue L, Abechi P, Kumar K, Rahmat J, Giwa A, Mwandira G, Olamilekan AM. Transcriptomic dysregulations associated with SARS-CoV-2 infection in human nasopharyngeal and peripheral blood mononuclear cells. bioRxiv. 2020 Jan 1.

Albert-Puleo M. Physiological effects of cabbage with reference to its potential as a dietary cancer-inhibitor and its use in ancient medicine. Journal of ethnopharmacology. 1983 Dec 1;9(2-3):261-72.

Post-infectious body odor

2022-01-12T19:23:00.006-08:00

Every infection has a distinct odor. It could be associated with changes in the gut microbiome. Besides, circulating B-cells from our immune system are also producing chemical odors that appear after viral infection. T-cell and cytokine involvement is also possible. Infections can change body odor for the worse. PATM or MEBO conditions could begin after an infection and linger thereafter.

COVID-19 is known to be associated with a specific odor. Early studies identified volatile compounds that discriminated COVID-19 from other conditions. Some of these compounds - such as fruity smelling ketones - are also associated with diabetes - a risk factor for Severe COVID-19 infection. Another compound, Heptanal, associated with lung cancer, can also predict the severity of the Coronavirus disease.

Dogs (and rats and other animals) can easily detect the smell of COVID-19. They are already helping during this pandemic - Massachusetts schools, for example, are using dogs to sniff out Covid-19. The dogs come to the schools weekly and work to detect cases in empty classrooms, auditoriums, cafeterias and gymnasiums, If Covid is detected, the authorities tell the health nurse who relays the information to the people affected.

Long COVID - when people continue to have symptoms of COVID-19 for months after their initial illness. - has a distinct smell as well. A paper posted today on MedRxiv tells that dogs can easily detect long COVID as well - in at least half of the cases.

Between May and October 2021, 45 Long COVID patients sent their axillary sweat samples to the National Veterinary School of Alfort. Average age of the patients was 45 (6-71) and 73.3% were female. No patient had been admitted in intensive care unit during the acute phase. Prolonged symptoms had been evolving for an average of 15.2 months (range: 5-22). Main symptoms of prolonged phase were intense fatigue (n=37, 82.2%), neurocognitive disorders such as concentration and attention difficulties, immediate memory loss (n=24, 53.3%), myalgias/arthralgias (n=22, 48.9%), cardiopulmonary symptoms (dyspnea, cough, chest pain, palpitations) (n=21, 46.7%), digestive symptoms (diarrhea, abdominal pain, reflux, gastroparesis...) (n=18, 40.0%), ENT disorders (hyposmia, parosmia, tinnitus, nasal obstruction, inflammatory tongue, dysphonia, sinusitis) (n=18, 40.0%) (table 1). 11 (24.4) patients had at least one positive SARS-CoV-2 serology before any vaccination, 29 (64.4%) had a negative SARS-CoV-2 serology and 5 (11.1%) had no serology results. Snapshot of the table shows some of the cases. Interestingly, patients with odor exhibited symptoms similar to long COVID sufferers in the MEBO community. This includes loss of smell and heart palpitations.

REFERENCES

Dominique GRANDJEAN, Dorsaf SLAMA, Capucine GALLET, Clothilde JULIEN, Emilie SEYRAT, Marc BLONDOT, Maissa BENAZAZIEZ, Judith ELBAZ, Dominique SALMON Screening for SARS-CoV-2 persistence in Long COVID patients using sniffer dogs and scents from axillary sweats samples medRxiv 2022.01.11.21268036; doi: https://doi.org/10.1101/2022.01.11.21268036