Rebuild your Health

There is increasing evidence that intestinal microbial dysbiosis has a role in the pathogenesis of systemic malodor conditions and other metabolic disorders. The most studied non-syndromic malodor condition Trimethylaminuria is usually inherited in an autosomal recessive fashion, which means that two mutations from both parents, both affecting abilities of FMO3 enzyme to catalyze the N-oxidation of trimethylamine into trimethylamine (eg, [Glu158Lys (rs2266782) and Glu308Gly (rs2266780)]), may be needed for a person to have symptoms. Yet genotype is not always predictive of phenotype, not even in this case.

Illustration by Monica Garwood

Studies have shown that the symptoms of metabolic inefficiencies, food intolerance and even allergies can be relieved by changing the composition of intestinal microbes and adjusting dietary components feeding these microbes - to encourage growth of microorganisms properly digesting problem ingredients. Lactose-digesting bacteria Lactobacillus acidophilus, Lactobacillus bulgaricus and Streptococcus thermophilus, for example, can help to digest lactose into useful compounds, instead of offensive gas. On the other hand, the low-FODMAP diet reduces gastrointestinal symptoms by reducing the food that bacteria ferment. For lactose-intolerance, however,  the "O" in FODMAPs - oligosacharides - can be beneficial as Galacto-oligosaccharides (GOS) are useful prebiotics promoting the growth of the right microorganisms. 

Rebuilding the network of microorganisms on and inside our bodies can help to improve the volatiles in the surrounding air, aka body and breath odor. Microbes associated with unpleasant odors include Anaerococcus, Corynebacterium, Campylobacter, and Propionibacterium [1], Gardnerella, Alloprevotella, Sutterella, and species of Candida. Microbes associated with improvements in odors include archaebiotic Methanomassiliicoccus luminyensis, Lactobacillus pentosus KCA1, and Lactobacillus salivarius, but there are more, working together and relying on each other. Our studies (see protocols of microbiome [2] and volatilome [3] trials published on Medrxiv)  identified several microbial strains and volatile compounds associated with improvement of malodor symptoms. We are currently summarizing our results and plan to publish it. Development of personalized protocols and defining the right compositions of probiotics and prebiotics is a long-term research endeavor. Meanwhile, be your own best medical researcher and take control of your wellbeing: 

Step 1: Pull out your fitness journal and create an action plan

• Analyze your diet, everyday activities, exercise and sleep patterns to make initial guesses about things that could be triggering your flareups or making you feel better. Write out a list of these things. 
• Break your goal into small steps and milestones. For example: if you have fructose as a potential trigger on your list, go fructose free for a week. An earlier survey of about 100 body odor and halitosis sufferers indicated stress (34%), food (25%) and environment, including the weather and perfumed products (15%) as main triggers of odors or PATM. Make sure you are not missing something in your diet - like Zinc, Vitamin C, or Vitamin D - insufficient amounts of these vitamins and minerals could also contribute to PATM. 
• Develop metrics for evaluating progress. Some people can't objectively evaluate their malodor or PATM condition. Try to find a trust buddy or take note of how the people around you react when you’re in close proximity. For example, pay attention to the space people leave between you and themselves (assuming COVID-19 is behind us and the 6-feet rule no longer applies!)

Step 2: Change your diet, physical activity and behavior

• Intestinal lining is regenerating every five to seven days, so you need to stick to your diet for at least a week to notice improvements in your symptoms. Most elimination diets are actually recommended for about 3–6 weeks, to allow the antibodies (negatively reacting to problem food components) dissipate. So if your diet seems to be helping, extend it to 3 or 6 weeks. 
• If it is not helping, try the next thing on your list. It should not be just diet - one study showed that bad breath was associated with abnormal sleep patterns. Perhaps you need to reevaluate your clothing material, temperature an humidity or mycotoxins in the environment? Are you getting enough sunlight ? Does your home have a healthy microbiome? Try to eliminate the triggers one at a time. No need to reduce your overall food intake, many people observe malodor or PATM flareups when they are hungry & undernourished. Try to train your body to digest more fiber - but start adding them to your diet little at a time, on weekends when you can safely experiment.   

Step 3: Let go of past hurts

• Stop dwelling on the past. You have the power to change your future. Learn how to express confidence with your body language. Pretend you are comfortable in presence of other people and they will learn to be comfortable in yours. 

RFRERENCES

1. 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 Dermatology. 2020 Nov 4;3(1):e10508.

2. Gabashvili I.S. Dynamics of the Gut Microbiota in MEBO and PATM conditions: Protocol of a fully remote clinical study. medRxiv. 2020 Aug.24. medRxiv 2020.08.21.20179242; doi: https://doi.org/10.1101/2020.08.21.20179242

3. Gabashvili I.S. Effects of diet, activities, environmental exposures and trimethylamine metabolism on alveolar breath compounds: protocol for a retrospective case-cohort observational study medRxiv 2021, Jan. 26 2021.01.25.21250101; doi: https://doi.org/10.1101/2021.01.25.21250101

New Paper Reveals Insights into Bacteria that Live on Your Skin and in Your Gut

What do MEBO (metabolic body odor), PATM ("People are Allergic to ME" condition) and TMAU (trimethylaminuria) have in common - beside the obvious:  airborne substances that make people feel uncomfortable?  New paper published in JMIR Dermatology - Cutaneous Bacteria in the Gut Microbiome as Biomarkers of Systemic Malodor and PATM Conditions - demonstrates: it's microorganisms that live on the skin and can be also present in the gut. The results of a clinical trial reported in this paper showed that the same microbes can modulate severity of odor or allergic reactions in others independently of genetics and trimethylamine metabolism. 

Researchers long suspected that there was a link between gut and skin health. Recent studies have confirmed it for a number of inflammatory skin diseases - such as psoriasis, rosacea, acne and atopic dermatitis. Microbes have been also suggested as targets for treating TMAU, a disorder that causes the body to constantly emit foul odor - from the skin, the mouth and the nose - via skin or fecal microbiome transplantation, antibiotics and probiotics. However, existing treatments are too broad, can lead to other health problems and lack understanding of precise targets and mechanisms. 

The paper shows that MEBO and PATM conditions don't always arise because of the decrease in microbial diversity. About half of the people might be lacking in microbial richness, but another half has too many different bacterial species to handle. 

The figure shows results of 22 study volunteers that were able to observe both flare-ups and improvements in their condition. The Y axis shows changes in microbial diversity vs abundances of selected bacterial species (X axis) for 12 female and 10 male participants. The arrows are labeled with 3 or 4 digits - the last digits of MEBO ID. Beginning of the arrow shows participants' microbial diversity and proportion of skin microbes in the gut during flare-ups, the end of the arrow points to improvements. As this figure shows, the only exceptions to the conclusion that the fewer cutaneous bacteria in the gut, the fewer skin emanations were 1214, 1287 and 1307. All of them observed very minor if not negligible (and easy to misinterpret) improvement of their condition (flare-ups happening from “all the time” to “most of the time”). 1214 was seen by a professional dermatologist, who concluded that a diagnosis of bromhidrosis didn’t seem warranted. 1307 had undergone a Botox procedure to treat hyperhidrosis, but was still experiencing symptoms (and, from our results, large fluctuations in odorous skin bacteria). 1287 did not report any skin odors and noted only halitosis. 

Read the paper to learn more and stay tuned for more details as they develop.

REFERENCE

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

The Many Genes of TMAU

Twenty years ago Trimethylaminuria was linked to mutations in the FMO3 gene. It turns out there are many more genes that can lead to this condition. 

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Microbiome and TMA metabolism

Original article at Aurametrix

We are still waiting for the 4th batch of sequences/taxonomies and are incorporating more data from different sources for our NCT03582826 study, but have already started looking at the available data. 

Our previous trials showed that while there is no one-size-fits-all solution to MEBO and PATM symptoms, some metabolite measurements and self-reported data can distinguish different subtypes of these conditions with very high accuracy. 

Hence, we may need different treatments for sufferers with different metabolism - for example, abilities to process sugar in their food or higher production of putrescine  in urine (could it be due to pseudomonas and enterobacteria in the gut?).

Our previous studies had much fewer variables differentiating MEBO subtypes and fewer participants (NCT02692495: 16 viable samples from 11 men and 5 women; NCT02683876: 15 viable samples from 10 women and 5 men). We are now collecting the biggest ever MEBO dataset for the current study,  NCT03582826, with about 5 times larger number of participants than previous studies. One of the questions asked in QoL survey was whether participant's condition was 

active/progressing, regressing or they were in remission. We decided to start our exploratory analysis from the subset of sufferers with "disappearing" symptoms - when participants felt they were on the road to improvement. The figure above shows a quick-and-dirty model describing how compositions of just 4 microbes could predict quality of life for these participants. Interestingly, these bacteria did not seem to be responsible for their MEBO or PATM symptoms, only overall wellbeing. The figure on the left shows how just one class of bacteria  - Actinobacteria - correlates with the severity of MEBO symptoms in those whose condition is improving. It's very noisy, but it seems that increasing numbers of this bacteria  (responsible for the pleasant smell of rain) helps to improve odor. Yet, look what happens when we throw in data from those with active disease or in remission (right section of the figure above) - the pattern is completely lost. Even more so, looks that those who already achieved remission care less about this bacterium and sometimes even slightly benefit (at least, in their own opinion) if they slightly reduce its population. Obviously, we need to subdivide the data better before attempting to build predictive models and look at a lower level of microbial hierarchy.  

A quick-and-dirty principal component analysis of available samples vs all microbial species (figure on the right) shows that our research participants that tested negative for TMAU have different microbial profiles than those who tested positive, and microbiome for TMAU1 is different from TMAU2. 

So far, we have over 40 samples of those negative to TMAU1 and TMAU2, and over 30 samples of those diagnosed as either TMAU1 or TMAU2, dozens of samples of those with PATM with or without body odor or bad breath.  Interestingly these groups significantly differ in the self-perceived severity of their symptoms. 

Average MEBO score is the worst for those diagnosed negative to TMAU. (The figures show average MEBO scores along with their variations) Surprisingly, it's the best for those diagnosed with the most severe form of TMAU - TMAU1! This shows that it's possible to learn to control symptoms even in extreme cases. 

PATM symptom severity is even lower than MEBO symptoms for TMAU-negative individuals. 

In our next posts we will be looking at the potential of microbiome for diagnosis of different sub-conditions, such as TMA1, TMA2, PATM and other subtypes. 

We'll be also looking at different subgroups of bacteria - such as Enterobacteria that reduces TMAO to TMA Multiple research studies including correlation of metabolomic data from mixed microbiota fermentation systems did not give a true picture of which members of the gut microbiota were responsible for converting TMAO to TMA, and we hope to get a better insight.  

We also have 21 sets of "good" and "bad" days for the same individuals that will help us to understand what improves or worsens MEBO and PATM symptoms.

Big thanks to all those who were able to complete the study - we know that it was quite a challenge for some! Thanks to those who contributed at least one sample along with the QoL questionnaire. Thanks to all who donated their samples, even though they had to pay for it out of their own pocket. Let's continue to work hard together to find the solution.

REFERENCES

Hoyles L, Jiménez-Pranteda ML, Chilloux J, Brial F, Myridakis A, Aranias T, Magnan C, Gibson GR, Sanderson JD, Nicholson JK, Gauguier D. Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota. Microbiome. 2018 Dec;6(1):73.

Qiu L, Tao X, Xiong H, Yu J, Wei H. Lactobacillus plantarum ZDY04 exhibits a strain-specific property of lowering TMAO via the modulation of gut microbiota in mice. Food & function. 2018;9(8):4299-309.

Gabashvili IS. Community-led research discovers links between elusive symptoms and clinical tests. bioRxiv. 2017 Jan 1:139014.

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Update on Clinical trial NCT03582826:  Microbial Basis of Systemic Malodor and PATM Conditions

Recruited: 110 participants

Participated in the study (at least partially): 74

    Submitted 3 or more samples: 48
    Submitted 2 samples: 13
    Submitted 1 sample: 13

Studying body odor: one step at a time

Unpleasant body odors could be a sign of a disease. But even when the cause of the disease is known - an example is trimethylaminuria or TMAU - there are no one-size-fits-all solutions. Elimination of choline and other essential nutrients from diet can be harmful and unhelpful.  Everyone has their own unique needs, with individual combinations of foods, activities and optimal environmental conditions.

An earlier survey of about 100 body odor and halitosis sufferers indicated stress (34%), food (25%) and environment, including the weather and perfumed products (15%) as main triggers of odors. 23% of sufferers did not know what the trigger was.

Our study seems to have less unknowns. As you see from the picture, 60% of participants have both body odor and halitosis. Only 22% of participants were diagnosed with TMAU, one third has IBS, one third has environmental sensitivities (mostly pollen and mold allergies, but some have dust mite and pet allergies and chemical sensitivities). Over 60% of participants reported sensitivities to specific foods. Most frequent was lactose sensitivity.

It is known that a specific diet, infections and diseases have major impact on variations in human body odor.  Some of our early results on fatty and ammonia types of odors identified a few food ingredients and their maldigestion as potential causes. Our next posts on musty and smoky odors, as well as unpleasant odors in general will tell more.

e-mail to

 for more information

And stay tuned for results!

REFERENCES
Jan Havlicek, & Pavlina Lenochova (2008). Environmental effects on human body odour Chemical Signals in Vertebrates DOI: 10.1007/978-0-387-73945-8_19

Havlicek, J., & Lenochova, P. (2006). The Effect of Meat Consumption on Body Odor Attractiveness Chemical Senses, 31 (8), 747-752 DOI: 10.1093/chemse/bjl017

Moshkin M, Litvinova N, Litvinova EA, Bedareva A, Lutsyuk A, Gerlinskaya L. Scent Recognition of Infected Status in Humans. J Sex Med. 2011 Dec 6. doi: 10.1111/j.1743-6109.2011.02562.x.

The Road to Ammonia

Why do I smell like Ammonia? This question, in thousands of variations, has been asked over and over again at every major question/answer site, especially teen, bodybuilding and athletic forums.

The Internet provides plenty of opinions.

Medical sites talk about diseases like chronic kidney failure, hepatic cirrhosis or H. pylori infection. Fitness sites recommend drinking more water, reevaluating protein sources and eating more carbohydrates.

What are these diet-odor links? And what's the Science? Ammonia may be formed during the alkaline hydrolysis and deamidation of proteins - by our own metabolism and the metabolism of microbes that call us home. If our kidneys can't handle the load of nitrogen, it's excreted as ammonia in sweat. Excretion increases 10 times as temperature goes from 70 to 100 Fahrenheit.

Aurametrix is a breakthrough analysis tool that correlates users' actions and reactions based on what information they enter into the system. Preliminary correlations in the Aurametrix knowledge base show exactly what's expected: excess protein does lead to ammonia-like odor.

But wait a minute - does it say the same about excess fat?

An  example provided by one of our users is very interesting. The user logged a few foods he thought were contributing to odor. These were different odors according to the user - ranging from "Ammonia-like" to "Fishy", sharp, cloying and stale. Aurametrix, however, recognized that all these odors described by the user may be related to nitrogen-containing compounds.  When these three data points were analyzed along with four foods that the user did not associate with any odors, Aurametrix displayed only one result:

Based on your Aura entries, the following may be contributing to "Ammoniacal odor" in a 3 hour timeframe:

• Hexadecanoic acid (when consumed more than 0.7 grams, up to 1.19)

Hexadecanoic acid  - commonly known as Palmitic acid - is one of the most common saturated fatty acids in the Western diet. Palm oil and coconut oil contain especially high levels of this acid. What effect does this acid have on metabolism? It down-regulates glycose metabolism and protein metabolism, affecting Calcium or mRNA binding proteins [1]. So there may very well be a connection!

Want to connect the dots to your own health and wellbeing and see what you have in common with others?

Write to:

References

Hovsepyan, M., Sargsyan, E., & Bergsten, P. (2010). Palmitate-induced changes in protein expression of insulin secreting INS-1E cells Journal of Proteomics, 73 (6), 1148-1155 DOI: 10.1016/j.jprot.2010.01.012

Trabue S, Kerr B, Bearson B, Ziemer C. Swine odor analyzed by odor panels and chemical techniques. J Environ Qual. 2011 Sep-Oct;40(5):1510-20.

Ito, Shigeji; Kohli, Yoshihiro; Kato, Takuji; Abe, Yoshimichi; Ueda, Takashi
Significance of ammonia produced by Helicobacter pylori. European Journal of Gastroenterology & Hepatology. 6(2):167-174, February 1994.

Qiu, Y.T., Smallegange, R.C., Van Loon, J.J.A., Takken, W. 2011 Behavioural responses of Anopheles gambiae sensu stricto to components of human breath, sweat and urine depend on mixture composition and concentration. Medical and Veterinary Entomology 25 (3), pp. 247-255

Enrique Wolpert, M.D., Sidney F. Phillips, M.D., and W. H. J. Summerskill, D.M. Ammonia Production in the Human Colon — Effects of Cleansing, Neomycin and Acetohydroxamic Acid N Engl J Med 1970; 283:159-164

V Bhatia, R Singh, S K Acharya Liver: Predictive value of arterial ammonia for complications and outcome in acute liver failure. Gut 2006;55:98-104 Published Online First: 15 July 2005 doi:10.1136/gut.2004.061754

Consolazio, C.F., Nelson, R.A., Matoush, L.O., Canham, J.E. Nitrogen excretion in sweat and its relation to nitrogen balance requirements. J Nutr. 1963 Apr; 79:399-406.

Ammonia in personal care products:
After Bite ointments
Hair dyes

Ammonia in household products:
Ammonia Removing Products
Glass Cleaners
Kitchen Cleaners