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

get New Posts by EMAIL : Enter your email address :

---

A EURORDIS and NORD Member Organization

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.

get New Posts by EMAIL : Enter your email address :

---

A EURORDIS and NORD Member Organization

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

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

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

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