Showing posts with label Research. Show all posts
Showing posts with label Research. Show all posts

Saturday, August 26, 2023

Chronicles of Community-Driven Research: The Evolution of MEBO and PATM Studies

In the ever-evolving landscape of medical science, the untangling of medical mysteries often hinges not just on technological advancements or expert researchers, but on the active involvement of community members. Community efforts have been instrumental in the identification and understanding of elusive conditions MEBO (Metabolic Body Odor) and PATM (People Are Allergic to Me).

Late 1990s - early 2000s: The Dawn of Online Support Forums 

Before the conditions were officially named, online forums like MSN Body Odor Support Forum, ibsgroup.org, Yahoo TMAU group, and Curezone BO & Halitosis and TMAU forums served as early platforms for sufferers to discuss their symptoms. 

At this time, Trimethylaminuria (TMAU) was a scarcely recognized condition, and diagnostic tests were both costly and geographically limited. Trimethylaminuria support group, later established as foundation raises 35K and awards it to Dr. George Preti of Monell Center, the world’s only independent, non-profit scientific institute dedicated to interdisciplinary basic research on the senses of taste and smell.

2006-2007: Birth of MEBO and PATM Communities

In 2006, the acronym "PATM" was first coined by a sufferer, and by 2007, a dedicated PATM community was established on MedHelp. The initial post was reposted in PATM forum and garnered over 8,800 responses, signifying the start of a community-led initiative to explore the condition. While the term FBO (fecal body odor) emerged earlier and is still used on online forums,  it is often avoided due to its less appealing connotation. MEBO was coined by another individual suffering from a similar undiagnosed condition. This further fueled community-driven research and knowledge sharing among those affected.

2008: Broadening the Dialogue

The blog Bloodbornebodyodorandhalitosis.com is launched, later transitioned to meboblog.com. This year also saw more in-person meetups and community surveys, including one by pharmacist Arun Nagrath that received about 100 responses. 95% of responders was trying to seek medical help, over 90% thought that their doctor was not knowledgeable nor confident in their recommendations. 


2009: Formalizing Research Efforts

MEBO Research Charity was founded in both the UK and Florida, spearheaded by Maria de la Torre. The first collaborative study with UK's Biolab was initiated, focusing on blood and urine tests. The results were subsequently published on the MEBO blog and clinicaltrials.gov (NCT02692495, principal investigator: Irene Gabashvili).

2010: Unveiling the Microbiome and Genetic Factors

At MEBO's 1st annual conference, held in Nashville, Dr. Gabashvili presents "Microbes and us," discussing the human microbiome's role in poorly understood conditions like idiopatrhic malodor and multiple chemical sensitivities (MCS). Previously, MEBO interviewed Metametrix about their GI Effects panel, which measured stool bacteria, fungus, and parasites with DNA analysis.  Metametrix, pioneer in diagnostics of nutritional insufficiencies and metabolic dysfunction,was later acquired by Genova Diagnostics.

Dr. Nigel Manning introduces 12 potential subtypes of TMAU. Out of 1,150 urine samples from 716 individuals collected between 1997 and 2009, 379 (53%) indicate significant TMAU presence. The launch of a new FMO3 genetic testing service promises to provide clearer diagnostic results. Additionally, a TMAU service dog program is initiated.

2011: The Advent of Genomic Data Sharing

Community members begin sharing genomic data, and MEBO critiques the limitations of 23andMe's FMO3 testing in blog posts. Dr. George Preti and his team at the Monell Center publish "Individuals reporting idiopathic malodor production: demographics and incidence of trimethylaminuria", revealing that only one-third of individuals with idiopathic malodor test positive for TMAU. New study from Oxford, proposes two genes coding enzymes, besides FMO3, NAT8 and PYROXD2, both with relatively uncharacterized functional roles, as potentially linked to TMAU. 

The second annual meetup in Washington, DC, focuses on the interplay between genetic mechanisms and holistic health. Skype conference call group is formed. 

2012: Empowering Patients Through Technology
A new MEBO study focusing on alveolar breath is initiated (NCT03451994). Aurametrix health management software is publicly launched, allowing patients to diagnose metabolic inefficiencies through digital food and symptom journaling. Karen James, MEBO UK’s Public Relations Director, publishes an article in the Royal College of General Practitioners (RCGP) journal InnovAiT, describing the life of a TMAU sufferer. For iGEM competition,  student team from Fatih university genetically engineers bacteria producing geraniol and FMO3 to eliminate TMA odors. Their product, FreshEcoli, is supposed to work as a synthetic perfume. 

The Third Annual Meetup in Miami Beach features Dr. Elizabeth Shephard discussing pharmacogenetics and personalized medicine.

2013: Deepening Theoretical Insights
MEBO UK's scientific director, Dr. Colin Harvey-Woodworth, publishes an article proposing that some MEBO symptoms may be secondary to dimethylsulphidemia, a previously unidentified metabolic condition linked to DMGDH gene. Concurrently, a mediterranean study reveals that individuals carrying FMO3 mutations may not necessarily experience odor issues. The study finds that the TMA/TMAO ratio in urine samples from individuals with 158KK/308EG variants indicates reduced FMO3 activity, yet these individuals do not exhibit the hallmark fish-like odor commonly associated with trimethylaminuria. This data underscores the notion that the expression of trimethylaminuria symptoms is influenced by factors beyond the presence of specific genetic variants.

2014: Therapeutic Innovations
Dr. Jean-François Brugère proposes the therapeutic use of archaea to prevent trimethylaminuria and cardiovascular disease. The technique was patented but not yet tested in humans. MEBO's TMAU urine testing program is initiated, and the results  are discussed. Another student team from Paris University, genetically engineers skin bacteria by introducing a trimethylamine mono-oxygenase from a non-human bacteria Ruegeria pomeroyi, for iGEM competition. Dr. Aydin proposes new definitions for halitosis. Reddit TMAU and PATM groups are created. 

2015: Expanding Testing and new molecular targets
The MEBO Conference in Orlando distributes urine test kits based on choline challenges and discusses emerging trends in testing methodologies.

3,3-Dimethyl-1-butanol (DMB), which is a structural analog of choline found in some foods, such as balsamic vinegars, red wines, some cold-pressed extra virgin olive oils and grapeseed oils is demonstrated to inhibit TMA production by gut bacteria. DMB has potential as a therapeutic approach. Studies also show the inhibitory effects of Resveratrol on TMA production in mice, further expanding the scope of potential small molecule targets. Dr Stanley Hazen files a patent.

2016: Streamlining Diagnostic Approaches
MEBO collaborates with Professor David Wishart on a Urine Metabolomics study, registered as NCT02683876, involving Canadian participants. The study aims to explore simpler, non-challenge-based tests for diagnosis.

Several sufferers in the MEBO community report taking Resveratrol for a few months, with excellent results in decreasing or completely eliminating their odor symptoms while increasing consumption of foods high in choline, carnitine, and lecithin.


2017: Diagnostic Breakthroughs and the Social Media Shift

MEBO's Scientific Director, Irene Gabashvili, publishes the Biolab study on BiorXiv. The study reveals significant differences in intestinal permeability among participants based on body regions responsible for VOC emissions. In addition, the study identifies two subgroups of MEBO/PATM sufferers based on sugar intake. Due to the small sample size of 16 participants, the article remains a preprint. Unfortunately, the current structure and incentives of mainstream academic publishing favor well-funded research on common diseases and are less accommodating to research on overlooked rare conditions. 

A Monell Center Study published in BMC Medical Genetics delves into the genetic complexities of TMAU, revealing that not all cases are linked to the FMO3 gene. Although the choline challenge test confirmed a diagnosis of TMAU by revealing a high level of urinary TMA in all 10 subjects, genetic analyses revealed that the FMO3 gene appeared to be normal in four of the 10. Additional analyses revealed defects in several other genes that could contribute to the inability to metabolize the odorous TMA. No rare variants are found in PYROXD2 and a DMGDH, but there were associations with BHMT2, SARDH and SHMT1 genes, which directly interact with DMGDH in the gene network and may participate in the same pathway. At MEBO conference in Miami Beach, Professor Shephard talks about microbiome and diet

Armpit microbiome transplantation shows reduction in odor when performed from one sibling to another. 

Danny Kunz and his Citizen Research Group in Germany initiate a DNA sequencing study. Their simulations backed by large enzyme databases suggest that Thyroid-stimulating hormone (TSH) may play a role. Danny proposes a new name for the condition: Intestinal Metabolic Bromhidrosis Syndrome (IMBS).

Facebook's "Groups" feature spurs the creation of new private MEBO and PATM communities, marking a new era in community engagement and data sharing.

2018-2020: Advancing Research and Understanding

Microbiome study of MEBO and PATM communities is initiated, registered as NCT02683876

A Japanese paper confirms PATM as a physical condition connected to skin petrochemicals and microbes. Meanwhile a case report entitled "People allergic to me and body dysmorphic disorder" published in Asian Journal of Psychiatry is linking a case to a relatively common psychiatric disorder characterized by preoccupations with perceived defects in physical appearance. The average age of BDD onset was previously estimated as 15 with symptoms lasting 18 years on average without proper treatment. The prevalence of BDD is thought to be 0.7-2.4% in the general population, but the condition remains underdiagnosed and poorly understood.

Results from the MEBO-Wishart study align with previous MEBO/PATM findings but highlight the limitations of morning urine tests. A new PATM survey is conducted by an independent PATM ufferer/researcher. Average age of responders is 28. Mononucleosis due to CMV is proposed as the cause of PATM.

UC San Diego student team explores the enzymatic breakdown of TMA. New gene SELENBP1 is proposed to explain metabolic halitosis. A patent on using Mikania plant extract to inhibit the conversion of choline to trimethylamine (TMA) is filed and granted, based on an earlier patent for using this plant to suppress body odor. 

RareConnect is established as a platform for those affected by rare diseases, including MEBO Research members. MEBO Research becomes a member. Unfortunately, by the end of 2023 it will be shut down, not being able to compete with Facebook and Reddit. Yahoo Groups shut down on December 15, 2020, for the same reason. New Instagram and WhatsApp groups are created.

New paper "Treatments of trimethylaminuria: where we are and where we might be heading" is published. It reviews Fecal microbial transplantation (FMT) that was not especially successful for reducing TMA or was only transiently effective as the symptoms returned one year after treatment. Antibiotic treatment is also transiently effective in some patients and completely ineffective in others.  Future research directions include gene therapy, enzyme replacement/enhancement therapy and gut microbiome modulation. 

Peer-reviewed paper examining the microbiome traits of individuals self-identifying with PATM and MEBO (NCT02683876) is published in JMIR Dermatology. The study reveals that both MEBO and PATM share increased levels of malodor-associated skin bacteria compared to non-MEBO/non-PATM groups, correlating with severity of self-reported symptoms. However, both populations exhibit significant heterogeneity.

2021-2023: Ongoing Challenges and Future Directions

A COVID study identifies flare-ups in 10-15% of the MEBO population post-infection and vaccination, possibly related to microbiome and hormonal fluctuations (NCT04832932; peer-reviewed paper published in JMIR Formative Research). 

A cysteine challenge test for hydrogen sulfide production is suggested. Florida State University's iGem team proposes a synthetic biology project for TMAU

New paper by Chris Callewaert explores various cutting-edge approaches to skin health, including genetically engineered probiotics and microbiome transplantation. While promising, the latter method currently lacks scalability for industrial applications. The paper also delves into skin bacteriotherapy, a technique involving the application of one or multiple pure bacterial cultures with health-promoting properties to cleansed or disinfected skin areas. Additionally, the study examines the use of prebiotics applied directly to the skin to encourage the growth of beneficial microbes. Each of these innovative approaches holds promise but also presents its own set of challenges.

A study by Professor Sekine in Nature Scientific Reports identifies volatile organic compounds as key differentiators between PATM sufferers and controls. These results align with our yet to be published findings from MEBO-Menssana Alveolar Breath Test Study (NCT03451994) and Microbiome study (NCT03582826). 

Despite these advancements, mainstream science remains largely uninterested in community-based research, leaving MEBO, PATM and TMAU without a definitive cure.

Wednesday, January 25, 2023

Food, Hormones and Odor Pollution

While there is not enough research on human odors, there are plenty of studies that can be related to this topic. Scientific papers published in January are about goats, fish, fermented food and biological waste. 

It is worth examining some of the latest findings and how they may be translated into take-home messages for humans.

1. Intermittent fasting could improve body odor. 

At least for fish. The study aimed to investigate the response of intestinal microbiota during 3 weeks’ starvation of largemouth bass (Micropterus salmoides), found that food deprivation helped to improve the odor of an economically important freshwater fish by reducing earthy-musty off-flavor compounds such as geosmin and 2-methylisoborneol. The study revealed that certain actinobacteria such as Microbacterium and Nocardioides were able to grow better than Mycoplasma, Pseudomonas, Acinetobacter, and Microbacterium when the fish were in a fasted state. This suggests that intermittent fasting may help to improve body odor by promoting the growth of beneficial bacteria and reducing the growth of odor-causing bacteria. However, more research is needed to confirm these findings in human studies. Besides, our own data show that people smell worse when starving themselves and it is a good idea to not go overboard. 

2. Adding fiber to diet and reducing stress levels can improve body odor. 

Korean native black goats (KNBG) are able to adapt to a wide variety of climatic conditions and foraging preferences. Twenty-four KNBG (48.6 ± 1.4 kg) were randomly allocated to one of four treatments featuring different dietary forage (high in fiber) to concentrate ratio (high forage [HF, 80:20] and low forage [LF, 20:80]), and a castration treatment (castration [CA] vs. non-castration [NCA] - aka higher levels of sex hormones, stress hormones). The animals were maintained on a free-choice feed and water regimen.

The intensity of a strong “goaty” flavor was remarkably enhanced when non-castrated KNBG were fed with the low forage diet. Better smelling goats had more hydrocarbons and ketones while worse smelling ones were higher in aliphatic aldehydes, possibly owing to the activity of testosterone, androsterone, and skatole. For volatile compounds, dichloromethane (chloroform-like odor) and m-xylene (plastic odor) were reported to be linked with the “strong lamb odor” influenced by dietary selection. 

10% fermented mixed feed supplementation (compared to 5% or 0%) helped to improve flavor of pork by increasing the contents of total aldehydes, (E,E)-2,4-nonadienal, dodecanal, nonanal and 2-decenal, along with inosine monophosphate. 

A healthy gut microbiome may positively influence sex hormones by regulating the appetite and reducing insulin resistance. Acute psychosocial stress, on the other hand, causes unhealthy fluctuations in sex hormone levels.  

Here are a few tables compiled from the goat diet/hormones article:

Microbe GenusCompounds positively correlatedCompounds negatively correlated.
FlexilineaC16:0 (Palmitic acid, oily smell)C18:2n6 (Methyl linoleate, oily odor), C18:3n3 (Linoleic acid, oily, low odor), PUFA
IhubacterC16:0 (Palmitic acid, oily smell)C18:2n6, C18:3n3 (Linoleic acid), PUFA
Ruminococcus-C16:0 (Palmitic acid, oily smell)
ChristensenellaC18:0 (Stearic acid), PUFAC16:1n7 (Palmitoleic Acid, Cardioprotective - smells like Old Books)
LachnoclostridiumC18:1n9 Oleic acid)C18:2n6, C18:3n3 (Linoleic acid),, PUFA
Treponema-C18:0 (Stearic acid), C18:3n3 (Linoleic acid), C20:4n6 (Arachidonic acid: from marine, at low concentrations, to intense orange-citrus and animal-like odor)
SucciniclasticumC18:1n7 (Vaccenic acid), C18:3n3 (Linoleic acid)-
DesulfovibrioC18:1n7 (Vaccenic acid)-
Blautia-C18:2n6 (Linolelaidic acid)
Rhabdanaerobium-C18:3n3 (Linoleic acid)
Gracilibacter-C18:3n3 (Linoleic acid)
Butyrivibrio-C18:3n3 (Linoleic acid)
ParaprevotellaC20:4n6, C22:4n6-
IntestinimonasC22:4n6-

This table summarizes the relationship between meat fatty- composition and rumen bacteria at the genus level. 

Higher levels of carbohydrates may promote the persistence and flavor formation of Z. rouxii (Zygosaccharomyces, a genus of yeasts in the family Saccharomycetaceae) in the moromi soy sauce, and it changes its aroma profile. Not sure if it is to the better or worse. 

3. Acinetobacter is associated with fish odor and the odor of biowaste. It is also associated with odor in MEBO and PATM populations - this is one of not yet published results of our microbiome study  (in addition to skin bacteria)

A study to be published in print in the February issue of "Science of The Total Environment", examined odor profiles of cooked and uncooked food waste.

Odor pollution often occurs in the initial decomposition stage of municipal biowaste, including throwing/collection and transportation. However, this aspect of odor impact from municipal biowaste has not been well studied. In Nie and colleagues' experiments, a practical dustbin (120 L) equipped with flux chamber and filled with three types of municipal biowaste was used to simulate garbage storage conditions. The result indicated that the emission rate of odor pollutants for uncooked food waste (UFW) represented a nearly linear growth trend, reaching the maximum (3963 ± 149 μg kg−1 DM h−1) at 72 h. Cooked food waste (CFW) increased rapidly from 8 h to 24 h, and then remain fluctuated, reached the maximum (2026 ± 77 μg kg−1 DM h−1) at 72 h. Comparatively, household kitchen waste (HKW) reached the maximum emission rate (10,396 ± 363 μg kg−1 DM h−1) at 16 h. Sulfide and aldehydes ketones were identified as dominant odor contributor to UFW and CFW, respectively. While aldehydes ketones and sulfides were both dominant odor contributor to HKW. Moreover, the microbial diversity analysis suggests that Acinetobacter was the dominant genus in UFW, and Lactobacillus was the dominant genus in CFW and HKW. In addition, it was evident that each odorous pollutant was significantly associated with two or more bacterial genera, and most bacterial genera such as Acinetobacter, were also significantly associated with multiple odorous pollutants. The variation of odorants composition kept consistent with microbial composition. The present study could provide essential evidence for a comprehensive understanding of odorant generation in the initial decomposition stage of municipal biowaste. It could contribute to setting out strategies for odor control and abatement in municipal biowaste management systems.

The highest emission was observed in household kitchen waste with alcohol esters.

The highest total odor activity values were observed in uncooked food waste.

Lactobacillus was the dominant genus in household kitchen waste and cooked food waste.

Acinetobacter was the dominant genus in uncooked food waste. 

The variation of odorants composition kept consistent with microbial composition.




REFERENCES

Lee J, Kim HJ, Lee SS, Kim KW, Kim DK, Lee SH, Lee ED, Choi BH, Barido FH, Jang A. Effects of diet and castration on fatty acid composition and volatile compounds in the meat of Korean native black goats. Anim Biosci. 2023 Jan 11. doi: 10.5713/ab.22.0378. Epub ahead of print. PMID: 36634653. download pdf

Zou S, Ni M, Liu M, Xu Q, Zhou D, Gu Z, Yuan J. Starvation alters gut microbiome and mitigates off-flavors in largemouth bass (Micropterus salmoides). Folia Microbiologica. 2023 Jan 13:1-2.

Lülf RH, Selg-Mann K, Hoffmann T, Zheng T, Schirmer M, Ehrmann MA. Carbohydrate Sources Influence the Microbiota and Flavour Profile of a Lupine-Based Moromi Fermentation. Foods. 2023 Jan 2;12(1):197. doi: 10.3390/foods12010197. PMID: 36613413; PMCID: PMC9818829.

Nie E, Wang W, Duan H, Zhang H, He P, Lü F. Emission of odor pollutants and variation in microbial community during the initial decomposition stage of municipal biowaste. Sci Total Environ. 2023 Feb 25;861:160612. doi: 10.1016/j.scitotenv.2022.160612. Epub 2022 Nov 29. PMID: 36455726.

Shi Q, Tang X, Liu BQ, Liu WH, Li H, Luo YY. Correlation between microbial communities and key odourants in fermented capsicum inoculated with Pediococcus pentosaceus and Cyberlindnera rhodanensis. J Sci Food Agric. 2023 Feb;103(3):1139-1151. doi: 10.1002/jsfa.12321. Epub 2022 Nov 24. PMID: 36349455.

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

Search Odors (cdc.gov) - database of toxic chemicals

OdorDB: Home (yale.edu)

Friday, March 31, 2017

Giving the underserved the care they deserve

Nobody likes strong smells coming from other human beings. It's just that social convention: you are nice, if you smell nice, and you are a monster - like Shakespeare's Caliban - if you smell bad.

But it could be the brunt of the genetic or environmental misfortune



Wednesday, July 28, 2010

Hormonal Manipulation of Olfactory Cues, or How to Lose a Guy in 10 days

This post was chosen as an Editor's Selection for ResearchBlogging.org
Ring-tailed Lemur (Lemur catta) at Berenty Pri...Image via Wikipedia
Body odors are important cues used for social and sexual discrimination. As was shown many times, animals can easily smell age-, health- and genetics-related  differences.  Recent study of our large-eyed relatives, ring-tailed lemurs, demonstrate that drugs can alter body scents and change behavior.

Researchers examined changes in endocrine and  semiochemical profiles of sexually mature female lemurs treated with hormonal contraceptives during their breeding season. Genetic diversity and kinship were estimated using 11–14 microsatellite loci and pairwise genetic distances. Gas chromatography-mass spectrometry (GCMS) was used to detect the volatile compounds in odor. A rater blind to the treatments scored lemur male behavior in regards to female odors. 

The conclusion? Contraceptives change chemical ‘signature’, minimizing distinctiveness and genetic fitness cues. No more can the males determine which females are genetically and physically beautiful. All contracepted females lost their individuality and started to smell funny.  

What about hormones and chemicals in our food?  Maybe one day humans will wake up and realize that something is lost? May it will happen  sooner rather than later...

For those interested in helping with our research of human environmental malodor - check our studies or this call for collaboration.   

ResearchBlogging.org

Jeremy Chase Crawford,, Marylène Boulet,, & Christine M. Drea (2010). Smelling wrong: hormonal contraception in lemurs alters critical female odour cues Proc. R. Soc. B published online before print July 28, 2010


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