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

The Breathprint of COVID-19

Bad breath in those infected with COVID-19 might be the least of their problems. But studying it helps in understanding the mechanisms of this deadly respiratory disease and developing diagnostic tests. 

Dozens of confirmed cases of halitosis owing to active infection by SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) have been reported in the literature (Patel & Woolley, 2020; Riad et al, 2020)

Possible explanations were decreased salivatory flow due to angiotensin‐converting enzyme 2 receptor-mediated alterations in the tongue, a greater risk of bad breath for mouth breathers who are also more prone to halitosis and increased attention to odor when wearing face masks. Another likely explanation is bacterial co‐infections arising from the novel coronavirus.

DNA analyses of microbial communities in the respiratory tract of those infected with SARS‐CoV‐2 frequently detect abnormally high bacterial reads of Prevotella, Streptococci, Treponema, Veillonella and Fusobacteria, known to emit malodorous volatile sulfur compounds and volatile fatty acids (VFAs). In addition to odor, VFAs could impair T- and B-cell proliferation responses and cytokine production.

What molecules could we expect to find in a person infected with the novel coronavirus? Lamote and colleagues review dozens of (often overlapping) molecules detected in other infections. Among those are aliphatic alcohols, branched hydrocarbons, alkane derivatives, terpenes, dimethyl sulfide and other sulfur and nitrogen-containing compounds. Three aldehydes (octanal, nonanal, and heptanal) drew special attention as candidate biomarkers in pediatric SARS-Cov-2 infection (Berna et al., 2020). These three biomarkers demonstrated 100% sensitivity and 66.6% specificity. Analysis of breath in two groups of adults with median ages 40 and 60 identified aldehydes (ethanal, octanal), ketones (acetone, butanone), and methanol that discriminated COVID-19 from other conditions. Aldehyde Heptanal had significant predictive power for severity of the disease.

It has been shown that properly trained dogs  are able to detect an olfactory signature of SARS-CoV-2 infection with a specificity greater than 90%. Several clinical trials have been initiated to study biomarkers of COVID-19 in breath by e-nose and other technologies. Two studies have been already completed and one paper reported successful detection using Aeronose (Wintjens et al, 2020) with 86% sensitivity and negative predictive value of 92%. Gas Chromatography-Ion Mobility Spectrometry allowed differentiation of patients with definite diagnosis of Covid-19 from non-Covid-19 with about 80% accuracy and 82.4%/75% to 90%/80% sensitivity/specificity. 

REFERENCES

Patel J, Woolley J. Necrotizing periodontal disease: Oral manifestation of COVID‐19. Oral diseases. 2020 Jun 7.

Riad A, Kassem I, Hockova B, Badrah M, Klugar M. Halitosis in COVID-19 patients. Special care in dentistry: official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry. 2020 Nov.29

Lamote K, Janssens E, Schillebeeckx E, Lapperre TS, De Winter BY, Van Meerbeeck JP. The scent of COVID-19: viral (semi-) volatiles as fast diagnostic biomarkers?. Journal of breath research. 2020 Jun 29.

Berna AZ, Akaho EH, Harris RM, Congdon M, Korn E, Neher S, Farrej MM, Burns J, John AO. Breath biomarkers of pediatric SARS-CoV-2 infection: a pilot study. medRxiv. 2020 Dec. 7

Ruszkiewicz DM, Sanders D, O'Brien R, Hempel F, Reed MJ, Riepe AC, Bailie K, Brodrick E, Darnley K, Ellerkmann R, Mueller O. Diagnosis of COVID-19 by analysis of breath with gas chromatography-ion mobility spectrometry-a feasibility study. EClinicalMedicine. 2020 Oct 24:100609.

Wintjens AG, Hintzen KF, Engelen SM, Lubbers T, Savelkoul PH, Wesseling G, van der Palen JA, Bouvy ND. Applying the electronic nose for pre-operative SARS-CoV-2 screening. Surgical endoscopy. 2020 Dec 2:1-8.

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

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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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