Fusarium, the Microbiome, and the Many Possible Pathways of PATM

After years of collecting patient histories, correspondence, and laboratory reports, one impression has become increasingly difficult to ignore: there may not be one single underlying cause of PATM or MEBO. Instead, different people may arrive at a similar set of symptoms through different biological pathways.

We do have a growing list of possible culprits and triggers, and we are beginning to see that some patients can be matched by particular findings. But it remains a list—with many different candidates rather than one universal explanation. 

Last week, for example, we received a letter from a young woman in the United States who had experienced MEBO for approximately a decade. She was only recently diagnosed with biliary dyskinesia, a disorder affecting the movement of bile from the gallbladder.

This is not the first story of this type that we have encountered. In the past, we heard from a young man in China who had experienced PATM for approximately eight years and from a 37-year-old man in the United States who reported having PATM since he was 14. Both suspected problems with their gallbladder as a culprit.

These stories align with our observation that disturbances in different parts of the gastrointestinal system may sometimes contribute to a similar downstream phenomenon.

And then today, we received another intriguing history, this time from a man in Finland.

He believes that his PATM began following exposure to a water-damaged building and that Fusarium, a genus of fungi, may be involved.  Fusarium odoratissimum are explicitly named for their potent, recognizable odor and many strains produce damp, musty unpleasant smells. He subsequently had testing that detected mycotoxins associated with Fusarium, and he has developed a detailed hypothesis connecting fungal metabolism, intestinal processes, volatile organic compounds (VOCs), and the reactions experienced by people around him. This aligns with several other stories linked to mycotoxins, although those patients did not test specifically for fungi in their systems.

His interpretation is still a hypothesis. Nevertheless, Fusarium is another candidate that deserves to be investigated. 

Fungi and yeasts are still relatively understudied compared with bacteria, particularly when it comes to the human microbiome and gastrointestinal ecosystem.

At the same time, laboratory technology continues to evolve. Testing methods are becoming more sophisticated, and laboratories are expanding the range of microorganisms and metabolites they can detect.

That matters because what we are able to find depends, to some extent, on what we know how to look for.

The Finnish patient's testing was performed by Great Plains Laboratory, the same laboratory used by several other people in the PATM/MEBO community—along with Metametrix, Genova Diagnostics, Viome, and Biohm. We have not yet found one microorganism that is consistently present across all of these cases.

Interestingly, however, there are already some preliminary overlaps.

For example, among the people whose histories and laboratory results we have examined, Citrobacter freundii and E. coli have appeared in more than one case. These findings are far too limited to establish causation - both organisms can be found in the human gastrointestinal tract of individuals not reporting MEBO/PATM issues - but repeated observations are worth documenting and investigating.

Our microbiome study provides another piece of the puzzle. Using 16S rRNA sequencing, we found several microorganisms that appeared in common among participants. Some of these may represent opportunistic organisms or secondary changes resulting from another underlying disturbance, meaning that we may have been observing consequences rather than the original cause. I will be sharing more data from this study separately, but one important finding was the remarkably high heterogeneity among participants. Even with approximately 100 participants, the sample was not large enough to overcome that heterogeneity and identify a single consistent microbial signature.

This is another reason why I am increasingly hesitant to look for one universal culprit. The microorganisms we detect may sometimes be part of the downstream effects of whatever initially disrupted the individual's gastrointestinal ecosystem.

And Fusarium gives us yet another direction to explore.

 

PATM appears not to be a single disease with a single pathogen, but rather an umbrella for several conditions, just as similar symptoms in other medical conditions can arise from very different underlying problems.

One person might have a disorder affecting bile flow. Another might have bacterial dysbiosis. Another might have fungal involvement. Another might have a different gastrointestinal, metabolic, or systemic problem that we have not yet identified.

The common denominator may therefore not be the original cause, but rather what happens downstream.

Different disturbances could potentially alter the intestinal environment, microbiome, metabolism, or the volatile compounds released by the body. If those downstream changes are capable of producing similar external effects, they could potentially lead to what patients experience as PATM or MEBO.

Patient histories are not clinical trials, and an association between two findings does not establish causation. We also have to be careful with laboratory tests: detecting an organism, metabolite, or mycotoxin does not automatically tell us where it came from or whether it is responsible for someone's symptoms.

Nevertheless, patterns are worth recording.

If the same organism appears repeatedly in unrelated patients, that deserves investigation. If several people improve after treatment of a particular gastrointestinal disorder, that deserves investigation. If a fungal organism repeatedly appears in patients with similar symptoms, that deserves investigation too.

And if entirely different medical conditions appear to precede the same phenomenon, that may be an important clue in itself.

For now, our list remains a list.

But we might eventually map it to the different pathways that can lead to the PATM/MEBO phenomenon and to what those pathways have in common.

 

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
URL: https://derma.jmir.org/2020/1/e10508
DOI: 10.2196/10508

MEBO and PATM--associated multispecies microbiomes mostly from stool, but also skin, oral, nasal, and genital sites   https://www.ncbi.nlm.nih.gov/sra?linkname=bioproject_sra_all&from_uid=1413303

Ledoux, M.-P., Dicop, E., Sabou, M., Letscher-Bru, V., Castelain, V., Danion, F., & Herbrecht, R. (2024). Fusarium, Scedosporium and Other Rare Mold Invasive Infections: Over Twenty-Five-Year Experience of a European Tertiary-Care Center. Journal of Fungi, 10(4), 289. https://doi.org/10.3390/jof10040289 

 

Insights from a PATM sufferer’s Perspective on Potential Research Directions

In a letter MEBO received from Zhejiang, China, Bowei shares observations about PATM that he believes are important for scientists to study. His main points include:

• PATM Amplifies Nearby Smells, creating a “super-smell effect” that intensifies odors around PATM sufferers.

• PATM Likely Spreads Primarily Through Breath, as people with the condition seem to release most of the problematic components through their mouths and noses rather than their skin.

• PATM May Heighten Sensitivity to Allergens, making people nearby feel itchy or sneezy, especially in environments with dust or allergens.

• PATM May Be Widely Underreported or Misdiagnosed as a mental health condition.

• PATM Could Be Caused by Unique Microbes, potentially including rare bacteria living in the gut or on the skin. 

  

We agree with these insights but also think skin emissions may play a role, potentially intensified by breath. Our recent studies support these observations: our breath metabolome research revealed that PATM  amplifies certain enviromental compounds, like propylene oxide, while our microbiome study found increased numbers of odor-causing bacteria. We believe these bacteria are secondary to other, possibly rare microbes residing in the gut and on the skin. But there seem to be more than one type of these microbes.

Here is Bowei's original letter:

I am a PATMer from Zhejiang, China. Thank you very much for your attention to PATM. I am writing this email to provide additional details regarding the symptoms and suggest directions and content for subsequent research. Should you still be engaged in PATM research, the following content may be beneficial to your endeavors.

 

1. The core characteristic of PATM in terms of odor is probably to amplify the odor of other gases. This is an imperceptible feature. Many people with PATM believe their body odor is severe. In fact, the root cause may not be the odor itself, but that PATM will amplify the smell of other olfactory gases. It not only amplifies the smell of PATM patients themselves, but also amplifies the smell of other people and objects in the surrounding environment. The principle may be that substances similar to agglutinogens gather some odor molecules in the air together, allowing more olfactory substances to contact the olfactory epithelium almost at the same time. The result of this effect in the brain is that a strong odor is smelled, while in fact the overall concentration of odor molecules in the air may not change significantly. At the same time, PATM has a special symptom of easily picking up odors from the environment, which may be related to the speculated principle of agglutination. Therefore, the gas released by PATM may have some gas components with higher content than that of normal people. These components may just be more easily aggregated by PATM agglutinogens, leading to excessive absorption and excessive release of PATMers, but not necessarily excessive production in their bodies. Some PATMers have repeatedly verified the characteristics of amplified odors in daily life, but there remains a lack of scientific, rigorously controlled experiments to substantiate this. Amplified odors are very difficult to detect, but I think it is the core factor that causes trouble for PATM. Should this pique your interest, you might consider designing an experiment to prove this hypothesis, which I believe would be highly advantageous.

 

2. Gases exhaled orally and nasally may be the primary means by which PATM releases abnormal components. The quantity of abnormal components exhaled through the mouth and nose per unit time may significantly exceed the amount released by the skin of the entire body. If feasible, incorporating a method for collecting exhaled gases from the mouth and nose could be beneficial. Moreover, utilizing the real-time exhaled gases of PATM patients for experiments may be preferable to remote collection, as the core components might be unstable.

 

3. PATM may induce allergies due to an "amplification" effect rather than direct effects.  According to the experience of some PATMers, the more "dirty" the environment, the more likely PATMers are to cause allergic reactions in people around them. It may be that PATM does not directly produce substances that stimulate human allergies, but in some way makes potential allergens more irritating, or makes people more susceptible to allergies. I am uncertain if you plan to verify whether the gases released by PATM cause changes in specific physiological indicators of humans or animals. If the gas of PATM alone cannot cause obvious changes in allergic indicators, it will be helpful to consider adding common potential allergens, or simply making the environment "dirtier", to verify the amplification effect of PATM in this regard. That is, substances that normally do not cause changes in allergic indicators in humans or animals may cause significant changes in related indicators in humans or animals after exposure to PATM gas.

 

4. The number of people suffering from PATM may be much higher than previously estimated. It is likely that more PATM sufferers are diagnosed with mental illnesses, and they do not use the name PATM to refer to their symptoms. At the same time, I am quite certain that PATM gas will not only indirectly cause psychological problems, but more importantly, it will directly cause abnormalities in the mental system (both PATMers and people around them will experience abnormalities), such as irritability, brain fog, fatigue, and abnormalities in certain related indicators. In this regard, I suggest finding people with PATM symptoms to serve as the providers of PATM gases for the experimental group, and finding some animals for comparative experiments to observe the animals' irritability, cognitive decline, fatigue, changes in related blood indicators, etc., to verify this point.

 

5. The root cause of PATM may be associated with a rare microorganism. Based on the very few cases of "infection" and recovery, perhaps the culprit of PATM is some rare microorganism that is difficult to spread but can be relatively stably colonized in the intestines or the human body after infection. Although there appears to be no evidence linking PATM to microorganisms, I personally think that the search for pathogenic microorganisms is the right direction.

 

I hope these suggestions prove helpful, especially the first point mentioned above, which is of great importance. In addition, according to ICD-11, PATM may be "officially" diagnosed as olfactory reference disorder (ORD); however, diagnosing PATM as a mental illness is clearly a misdiagnosis. Therefore, at present, it is deemed more important to first prove the various physiological effects caused by PATM gas and to correct the inaccuracies in ICD-11 regarding ORD. The abnormal gas composition can be considered in subsequent research. I suggest initially finding people with PATM symptoms, conducting animal comparison experiments on the various symptoms caused by PATM gas in the experimental field (the spatial distance between the experimental group and the control group should be as large as possible to avoid gas flow affecting the results), and then proceeding with subsequent research in the order of gas properties, gas composition, microbial species, microbial location, and decolonization.

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Bowei hopes that researchers will investigate these ideas, which may improve our understanding of PATM and help develop effective treatments. Initial studies could focus on isolating and identifying gas compounds and microbial markers unique to PATM sufferers, followed by animal model tests to assess the physiological and neurological responses to PATM-related gases. This perspective adds to the call for both empathy and rigor in the exploration of rare conditions like PATM.

 

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