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

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

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.

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The Smell of Life

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.

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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

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

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

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

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.

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