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 Genus	Compounds positively correlated	Compounds negatively correlated.
Flexilinea	C16:0 (Palmitic acid, oily smell)	C18:2n6 (Methyl linoleate, oily odor), C18:3n3 (Linoleic acid, oily, low odor), PUFA
Ihubacter	C16:0 (Palmitic acid, oily smell)	C18:2n6, C18:3n3 (Linoleic acid), PUFA
Ruminococcus	-	C16:0 (Palmitic acid, oily smell)
Christensenella	C18:0 (Stearic acid), PUFA	C16:1n7 (Palmitoleic Acid, Cardioprotective - smells like Old Books)
Lachnoclostridium	C18:1n9 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)
Succiniclasticum	C18:1n7 (Vaccenic acid), C18:3n3 (Linoleic acid)	-
Desulfovibrio	C18:1n7 (Vaccenic acid)	-
Blautia	-	C18:2n6 (Linolelaidic acid)
Rhabdanaerobium	-	C18:3n3 (Linoleic acid)
Gracilibacter	-	C18:3n3 (Linoleic acid)
Butyrivibrio	-	C18:3n3 (Linoleic acid)
Paraprevotella	C20:4n6, C22:4n6	-
Intestinimonas	C22:4n6	-

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)

Current Trends in Deodorization

In the Victorian era, people would wash off with a sponge soaked in cool water and vinegar, use sweat-absorbing pads in armpit areas and overwhelm unpleasant smells with perfume. The most popular scent was ambergris known for its marine, sweat and earthy scent with a fecal note (if not properly aged). Since energy was obtained from burning of fuels, large amounts of sulfur were always present in the air, covering odors of animal and human waste released into river and streams. 

Engineers eventually designed centralized closed water sewage treatment systems and modern plumbing, enabling rigorous personal hygiene. But in the early 1900s, fear-based marketing convinced people that they smelled bad, and this turned niche deodorant trades into a $22 billion industry. Odorono (from "Odor? Oh No!") was one of the first antiperspirants at the forefront of this transformation. 

The use of antiperspirant deodorants has been declining in recent years due to their potential effect on health and environment, and the availability of more natural and organic alternatives. COVID-19 pandemics has also negatively affected the deodorant market. As a result, the demand for deodorization has decreased during these times. But innovation continues.

Across North America, the deodorants market witnessed growth of few brands creating antiperspirants intended for alternative body parts, such as hands, face, and feet. For example, Gamer Grip Hand Antiperspirant, designed for athletes to improve their grip, has a lasting fragrance for 4 to 6 hours. Neat 3B Face Saver is an antiperspirant gel for the face that can be applied before makeup. Carpe No-Sweat Face is a natural, sweat absorbing gelled lotion created with sweat absorbing ingredients like jojoba esters, vitamin B3, silica microspheres, aloe vera, and colloidal oatmeal.

In the early 2000s, new types of deodorants appeared on the market. Deo Perfume Candy, Swallowable Parfum, and Otoko Kaoru were designed as edibles, and the fragrance was supposed to be released from the user's mouth and nose. However, these products were eventually discontinued due to safety concerns, as well as their lack of popularity. 

Beginning in the mid-2000s, many clothing companies started incorporating silver nanoparticles into their products including nano-engineered anti-odor textiles. While the technology was initially developed for use in the medical industry (antimicrobial wound dressings), nano-porous materials in clothing presented another way to manage body odor. These materials offered the potential to make traditional deodorants old-fashioned or even obsolete. 

Ag nanoparticles, for example, are effective at slowing the growth of bacteria that cause body odor and itchiness. Nano-silver socks help in preventing bacterial and fungal growth. Haojey creates textiles comprising a TiO2 particle core to provide UV resistance, silver nanoparticles for antibacterial textiles, and nanobamboo for odor adsorption. Cotton treated with pomegranate and galnut extract showed excellent deodorizing performance against trimethylamine. Odor-free medical masks are fabricated using Polyvinyl Butyral and Eucalyptus Anti Odor Agent. Aloe Vera and Polyvinyl Alcohol (AV/PVA) electrospun nanofibers show excellent results suppressing growth of S. aureus bacteria (by ~25%) although not E. coli. A team from UC Berkeley introduced a way to reduce underarm sweating and odor by using a cross-linked microporous copolymer containing methacrylate and acrylate units. 

Unfortunately, many of nano-infused textile products are investigated as skin irritants. Besides, considerable amounts of Ag nanoparticles were found to be released on washing Ag nanoparticle integrated fabrics, which is highly toxic to aquatic life. 

Another trend in the world of skincare that started in the late 2000s was topically applied probiotics. 

Although the idea is not new, as research into the human microbiome began to uncover the role that probiotics could play in improving health, the use of probiotics, prebiotics and postbiotics to help combat odor-causing bacteria began to gain traction. Oral deodorizers with probiotics are already commonly found in the market in the form of chewing tablets, lozenges, and capsules. Topical probiotic formulations could exert anti-inflammatory effects by stimulating regulatory T-cells and release of anti-inflammatory cytokines such as IL-10, within the immune system, competing with odor-causing microbes for nutrients, and aggregating and displacing them. When applied to the skin, Lactobacilli, for example, exhibits antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, and Cutibacterium (formerly Propionibacterium) acnes. Topical microbiome transplantation (Roseomonas mucosa lysate cultured from healthy volunteers) is believed to improve atopic dermatitis by restoring epithelial barrier function and innate/adaptive immune balance as well as via inhibition of S. aureus growth. Nitrosomonas eutropha improves appearance of skin. Transplantation of microbiome enriched in S. epidermidis helped to reduce axillary malodor in siblings or other matching individuals. Bacteria responsible for odor emitted from the skin is known and is common for individuals suffering from a variety of odor disorders, including those with genetic variations in ABCC11, FMO3 and those with idiopathic malodor. The presence of these bacteria in the gut microbiome correlates with the intensity of malodor. Balancing composition of gut microbes will definitely help to improve the odor but may take a long time and require tailor-made diets. And it is not clear if "suicide substrate inhibitors" such as iodomethylcholine are sufficiently safe to use.

More than a dozen topical probiotic species have been found to have a unique spectrum of characteristics, including keratin adhesion, inhibitory action, organic acid production, and inhibition of biofilm formation, skin whitening, moisturizing, anti-aging, anti-wrinkle and removing body odor. A new bilayer vaginal tablet of Lactococcus lactis has been designed for the treatment of vaginal bacterial infections and could also help to combat unpleasant odors. And so could Nitrosomonas eutropha, although so far it was only proven to help with acne. Genetically modified bacteria are also being investigated as topical therapeutics. Candidate genes are Fillaggrin, LEKTI, IL-10, genes encoding growth factors and hormones. Studies of safety and efficiency are still, however, in very early stages. The application of high amounts of bacteria, could, for example, lead to a skin immune reaction with irritation and side effects as a result. It could also lead to infection. 

The skin microbiome is relatively stable and quickly restores after washing and skincare product application, even if they contain antimicrobials. The reason is, skin microbiome is actually derived from within the skin, the deeper stratum corneum layers, skin hair follicles and is connected to the gut microbiome. Skin microbiome transplantation methods are currently being investigated and showed some promising results although many challenges remain that need to be overcome. 

Probiotic-infused products and skin transplants are gaining popularity due to their ability to promote healthy bacteria growth on the skin, which can, for example, help reduce body odor. However, there is still a lack of strong scientific evidence of effectiveness and a lack of thorough understanding of side effects.  Probiotics are living microorganisms, which means that they are sensitive to environmental conditions and can be difficult to work with. This can make it challenging to incorporate probiotics into skincare products in a way that preserves their effectiveness and stability. Finally, there are regulatory issues to consider when it comes to introducing new probiotic-based skincare products to the market. In order to be sold as a cosmetic product, a skincare product must be safe and effective, and the manufacturer must provide evidence to support these claims. This process can be time-consuming and costly and may discourage some companies from investing in the development of new probiotic-based skincare products. 

Overall, while there is a growing interest in the potential benefits of probiotics, prebiotics and postbiotics for the skin, the development of new probiotic-infused skincare products is likely to continue to be slow and incremental as researchers and manufacturers work to understand more about how probiotics work and how they can be effectively incorporated into skincare products. 

It is likely that skincare products developed in the future will be tailored to specific genetic profiles, as researchers continue to learn more about the role that genetics plays in skin health and the skincare concerns that people may have. 

One example is a urea-containing moisturizer that could be effective for people with a certain genetic variation in the filaggrin gene, Transient erythema (reddening of skin) is a potential side effect. A number of genes (such as MC1R, ASIP and BNC2) are related to skin conditions including sun sensitivity, skin moisturizing function, oxidative stress, stretch marks, and skin inflammation and are being investigated in personalized skincare R&D. 

Gene therapy and enzyme replacement therapies have achieved some notable successes in recent years. For instance, the US Food and Drug Administration (FDA) approved Luxturna for a rare form of inherited blindness, and Kymriah using genetically modified T cells to attack cancer cells, in 2017. However, the costs of research and development and the risk of side effects are extremely high. 

As a result, it can be difficult to obtain funding for non-fatal conditions like TMAU (trimethylaminuria). Trinzyme, a company focused on enzyme replacement therapies, was founded in 2011 with the goal of developing treatments for TMAU. While the company was able to secure initial funding, it has not yet been able to deliver on its promise of a treatment for this condition. Despite these challenges, the potential for gene therapy and enzyme replacement therapies to revolutionize the way we treat and prevent diseases remains significant, and research and development in these fields continues to advance.

In 2022, several companies started testing their deodorizing cosmetic products intended to block smelly chemical trimethylamine, emitted from the skin if the liver cannot completely break down this product of essential nutrients. Spain-based perfume manufacturer Eurofragance has recently teamed up with a Barcelona Children Hospital on a project to neutralize the strong odor of those who suffer from trimethylaminuria (caused by genetic mutations that affect the FMO3 function of the liver). The hospital's program initially focused on pediatric subjects with primary carnitine deficiency, manifesting as metabolic encephalopathy, lipid storage myopathy, or cardiomyopathy. Since the patients are not able to process long-chain fatty acids to convert them into energy, the accumulation of toxic fatty acyl derivatives impedes gluconeogenesis and urea cycle function which, in turn, causes hypoketotic hypoglycemia, transaminase elevations, and hyperammonemia - hence fishy odor. Eurofragance solution has citrus notes blocking the fish odor receptors in the nose. This way the fishy odor does not disappear, but it is not perceived. Eurofragance designed body cream lotion with 1% fragrance, an eau de toilette with 5% fragrance and a body serum with 2% fragrance. Other businesses designing their own solutions were Nannic "Skin care by science", and stealth-mode teams from British and US companies. 

While there is still a lot more research to be done, the development of these new deodorizing cosmetic products has provided hope for those who struggle with trimethylaminuria and similar conditions.

REFERENCES

Callewaert C, Knödlseder N, Karoglan A, Güell M, Paetzold B. Skin microbiome transplantation and manipulation: Current state of the art. Computational and Structural Biotechnology Journal. 2021 Jan 1;19:624-31.

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

Gabashvili IS. Identifying subtypes of a stigmatized medical condition. medRxiv. 2019 Jan 1:19005223.

Habeebuddin M, Karnati RK, Shiroorkar PN, Nagaraja S, Asdaq SM, Khalid Anwer M, Fattepur S. Topical Probiotics: More Than a Skin Deep. Pharmaceutics. 2022 Mar 3;14(3):557.

Lee GR, Maarouf M, Hendricks AJ, Lee DE, Shi VY. Topical probiotics: the unknowns behind their rising popularity. Dermatology Online Journal. 2019;25(5).

Lee YH, Lee SG, Hwang EK, Baek YM, Cho S, Kim JS, Kim HD. Deodorizing performance and antibacterial properties of fabric treated with pomegranate and gallnut extracts compared with properties of commercial deodorizing and antibacterial agents. Textile Science and Engineering. 2016;53(1):45-54.

Myles IA, Earland NJ, Anderson ED, Moore IN, Kieh MD, Williams KW, Saleem A, Fontecilla NM, Welch PA, Darnell DA, Barnhart LA. First-in-human topical microbiome transplantation with Roseomonas mucosa for atopic dermatitis. JCI insight. 2018 May 5;3(9).

Qadir MB, Jalalah M, Shoukat MU, Ahmad A, Khaliq Z, Nazir A, Anjum MN, Rahman A, Khan MQ, Tahir R, Faisal M. Nonwoven/Nanomembrane Composite Functional Sweat Pads. Membranes. 2022 Dec 5;12(12):1230.

Yang J. Personalized Skin Care Service Based on Genomics. InInternational Conference on Health Information Science 2021 Oct 25 (pp. 104-111). Springer, Cham.

 

Olfactory Signatures and COVID-19

Olfactory disorders have a significant impact on human lives - be it a lost/distorted sense of smell or unpleasant odors affecting the sense of smell of others. 

Odortypes can be influenced by human leukocyte antigen (HLA) genes of the major histocompatibility complex (MHC), genes associated with stronger response to COVID-19 vaccine as well as the severity of this disease. HLA may also be related to people's perception of the odor of other people. 

Of course, these are not the only variables involved, and there are more potentially overlapping risk factors for olfaction, metabolic body odor (MEBO), including trimethylaminuria (TMAU), and COVID-19: FMO3, SELENBP1, HspA, UGT2A1/UGT2A2, etc. 

A new peer-reviewed paper reporting results of a decentralized observational study (NCT04832932) compared MEBO participants to general populations in respect to their response to COVID-19 vaccines and SARS-Co-V2 infections. 

Body odor flareups were observed in about 10% of malodor sufferers after vaccination, as preliminarily reported. This number was similar to flareups of other chronic symptoms in groups of participants with gastrointestinal and autoimmune disorders.  

Long-term worsening of body odor was observed by other researchers after COVID-19 vaccination in about ~1% of studied populations. Dry mouth leading to halitosis was 10 times more prevalent compared to flu vaccines. MEBO participants reported stronger reactions than general population pointing to genetic and microbiome influences beyond FMO3.  

A better understanding of systemic malodor conditions could offer leads for targeted therapies. Findings on genetic and microbiome overlaps between COVID-19 and MEBO could pave the way for precision medicine to address the unmet needs of odor sufferers.

REFERENCE

Gabashvili IS. The Incidence and Effect of Adverse Events Due to COVID-19 Vaccines on Breakthrough Infections: Decentralized Observational Study With Underrepresented Groups. JMIR Formative Research. 2022 Nov;6(11):e41914. DOI: 10.2196/41914. PMID: 36309347; PMCID: PMC9640199.

On Cabbage and Selenium Binding Protein 1

Mutations in the gene encoding Selenium Binding Protein (SELENBP1) on chromosome 1q21 were found in multiple individuals with extra-oral halitosis. These individuals had increased levels of methanethiol and dimethylsulfide in their breath perceived as unpleasantly cabbage-smelling. It was reported to worsen after drinking beer. 

The mutations responsible include rs1553204817 (OMIM: 604188.0001: c.1039G>T); rs758495626 (c.673G>T (p.Gly225Trp)), rs1357490520 (c.481+1G>A disrupting splice site), and rs1553204840 (c.985C>T)

SELENBP1 was identified as a methanethiol oxidase (MTO), catalyzing the conversion of methanethiol (H3C-SH) to hydrogen sulfide (H2S), hydrogen peroxide (H2O2) and formaldehyde (HCHO). If this enzyme is not properly functional, the body will be releasing more Methanethiol  - a volatile and toxic gas with the characteristic smell of rotten cabbage. We get this compound from food - not only the cancer-fighting cabbage family, including radishes, but also orange juice, pineapple, strawberries, asparagus, wheat bread, gruyere cheese, coffee, roasted filberts and even cooked rice. Water, cherries, apples, whole milk, spinach and citrusy fruits could counteract the odor in some individuals. 

Selenium binding protein1 (SELENBP1) has been also associated with a rare disease hypermethioninemia (sometimes accompanied by learning disabilities and neurological problems), several cancers and schizophrenia (downregulated at its onset and upregulated at later stages); hypertension and ischemic heart conditions. Dysregulation of SELENBP1 is common to Zika virus (ZIKV) and dengue infections, and Guillain-Barré syndrome. It was also found to COVID-19.

REFERENCES

Pol A, Renkema GH, Tangerman A, Winkel EG, Engelke UF, De Brouwer AP, Lloyd KC, Araiza RS, Van Den Heuvel L, Omran H, Olbrich H. Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis. Nature genetics. 2018 Jan;50(1):120-9.

Philipp TM, Will A, Richter H, Winterhalter PR, Pohnert G, Steinbrenner H, Klotz LO. A coupled enzyme assay for detection of selenium-binding protein 1 (SELENBP1) methanethiol oxidase (MTO) activity in mature enterocytes. Redox Biology. 2021 Jul 1;43:101972.

Lin X, Lin Z, Zhao X, Liu Z, Xu C, Yu B, Gao P, Wang Z, Ge J, Shen Y, Li L. Serum SELENBP1 and VCL Are Effective Biomarkers for Clinical and Forensic Diagnosis of Coronary Artery Spasm. International Journal of Molecular Sciences. 2022 Oct 31;23(21):13266.

Chau EJ, Mostaid MS, Cropley V, McGorry P, Pantelis C, Bousman CA, Everall IP. Downregulation of plasma SELENBP1 protein in patients with recent-onset schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2018 Jul 13;85:1-6.

Zhang X, Hong R, Bei L, Hu Z, Yang X, Song T, Chen L, Meng H, Niu G, Ke C. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition. Open Medicine. 2022 Jan 1;17(1):1390-404.

Moni MA, Lio’ P. Genetic profiling and comorbidities of zika infection. The Journal of infectious diseases. 2017 Sep 15;216(6):703-12.

de Melo CV, Bhuiyan MA, Gatua WN, Kanyerezi S, Uzairue L, Abechi P, Kumar K, Rahmat J, Giwa A, Mwandira G, Olamilekan AM. Transcriptomic dysregulations associated with SARS-CoV-2 infection in human nasopharyngeal and peripheral blood mononuclear cells. bioRxiv. 2020 Jan 1.

Albert-Puleo M. Physiological effects of cabbage with reference to its potential as a dietary cancer-inhibitor and its use in ancient medicine. Journal of ethnopharmacology. 1983 Dec 1;9(2-3):261-72.

Post-infectious body odor

Every infection has a distinct odor. It could be associated with changes in the gut microbiome. Besides, circulating B-cells from our immune system are also producing chemical odors that appear after viral infection. T-cell and cytokine involvement is also possible. Infections can change body odor for the worse.  PATM or MEBO conditions could begin after an infection and linger thereafter.  

COVID-19 is known to be associated with a specific odor.  Early studies identified volatile compounds that discriminated COVID-19 from other conditions. Some of these compounds - such as fruity smelling ketones - are also associated with diabetes - a risk factor for Severe COVID-19 infection. Another compound, Heptanal, associated with lung cancer, can also predict the severity of the Coronavirus disease.

Dogs (and rats and other animals) can easily detect the smell of COVID-19. They are already helping during this pandemic - Massachusetts schools, for example, are using dogs to sniff out Covid-19. The dogs come to the schools weekly and work to detect cases in empty classrooms, auditoriums, cafeterias and gymnasiums, If Covid is detected, the authorities tell the health nurse who relays the information to the people affected.

Long COVID - when people continue to have symptoms of COVID-19 for months after their initial illness. - has a distinct smell as well. A paper posted today on MedRxiv tells that dogs can easily detect long COVID as well - in at least half of the cases. 

Between May and October 2021, 45 Long COVID patients sent their axillary sweat samples to the National Veterinary School of Alfort. Average age of the patients was 45 (6-71) and 73.3% were female. No patient had been admitted in intensive care unit during the acute phase. Prolonged symptoms had been evolving for an average of 15.2 months (range: 5-22). Main symptoms of prolonged phase were intense fatigue (n=37, 82.2%), neurocognitive disorders such as concentration and attention difficulties, immediate memory loss (n=24, 53.3%), myalgias/arthralgias (n=22, 48.9%), cardiopulmonary symptoms (dyspnea, cough, chest pain, palpitations) (n=21, 46.7%), digestive symptoms (diarrhea, abdominal pain, reflux, gastroparesis...) (n=18, 40.0%), ENT disorders (hyposmia, parosmia, tinnitus, nasal obstruction, inflammatory tongue, dysphonia, sinusitis) (n=18, 40.0%) (table 1). 11 (24.4) patients had at least one positive SARS-CoV-2 serology before any vaccination, 29 (64.4%) had a negative SARS-CoV-2 serology and 5 (11.1%) had no serology results. Snapshot of the table shows some of the cases. Interestingly, patients with odor exhibited symptoms similar to long COVID sufferers in the MEBO community. This includes loss of smell and heart palpitations. 

REFERENCES

Dominique GRANDJEAN, Dorsaf SLAMA, Capucine GALLET, Clothilde JULIEN, Emilie SEYRAT, Marc BLONDOT, Maissa BENAZAZIEZ, Judith ELBAZ, Dominique SALMON Screening for SARS-CoV-2 persistence in Long COVID patients using sniffer dogs and scents from axillary sweats samples  medRxiv 2022.01.11.21268036; doi: https://doi.org/10.1101/2022.01.11.21268036

Worried about body odor?

You are not alone. According to pre-COVID surveys, over one third said the fear of smelling unpleasant left them feeling unhappy and unattractive. Many people who survived COVID-19 worry about their body odor getting worse post-infection.

A team of researchers from Virginia Commonwealth University surveyed 322 individuals with loss of smell or taste as a result of confirmed COVID-19 infection and found that about half of them felt depressed and worried about their body odor [Coelho et al., 2021].  Extrapolating results of other surveys, this translates into about 20% of those who got through COVID-19.  

The most frequently reported phantom smell (likely not actually there) is the odor of smoke or burned food [Frasnelli et al, 2004]. Interestingly, these are also the most frequently reported types of smells that long-COVID sufferers can't perceive, when others detect them. 

Temporary loss of smell is common. About 20% of population experience it sometime before the age of 75. This number increases to ~80% in older age. 

Loss of smell associated with viral infections, especially COVID-19 is much more prevalent. Sometimes it's the only symptom associated with this infection. A meta-analysis of published reports reveals that the overall prevalence of alteration of the sense of smell or taste following COVID-19 infection ranges between 31% and 67% in severe and mild-to-moderate symptomatic patients, respectively. Fortunately, in most (70-80%) cases it comes back in 6 month or longer. A higher recovery rate was highlighted for subjects who underwent influenza vaccination. 

REFERENCES

Coelho DH, Reiter ER, Budd SG, Shin Y, Kons ZA, Costanzo RM. Quality of life and safety impact of COVID-19 associated smell and taste disturbances. American Journal of Otolaryngology. 2021 Jul 1;42(4):103001.

Frasnelli J, Landis BN, Heilmann S, Hauswald B, Hüttenbrink KB, Lacroix JS, Leopold DA, Hummel T. Clinical presentation of qualitative olfactory dysfunction. European Archives of Oto-Rhino-Laryngology and Head & Neck. 2004 Aug;261(7):411-5. 

Maiorano E, Calastri A, Robotti C, Cassaniti I, Baldanti F, Zuccaro V, Stellin E, Ferretti VV, Klersy C, Benazzo M. Clinical, virological and immunological evolution of the olfactory and gustatory dysfunction in COVID-19. American Journal of Otolaryngology. 2022 Jan 1;43(1):103170.

Vaira LA, De Vito A, Lechien JR, Chiesa‐Estomba CM, Mayo‐Yàñez M, Calvo‐Henrìquez C, Saussez S, Madeddu G, Babudieri S, Boscolo‐Rizzo P, Hopkins C. New onset of smell and taste loss are common findings also in patients with symptomatic COVID‐19 after complete vaccination. The Laryngoscope. 2021 Nov 26.

FMO3 and COVID-19

Flavin-containing monooxygenase 3 (FMO3) enzyme is a seemingly insignificant enzyme that normally converts fishy-smelling trimethylamine (TMA) into a neutral trimethylamine-N-oxide (TMAO). The amounts of this highly specialized detoxifying enzyme are highly variable. It depends on the age, sex hormones, infections (estradiol and testosterone, hepatitis virus have been found to reduce FMO3 capacity), obesity traits and diseases such as diabetes. The difference can be up to 20-fold between individuals. Mutations in the FMO3 gene cause low metabolic capacity associated with the disorder trimethylaminuria (TMAU) that attracts little biomedical interest.  This condition, however, might matter more than it seems.

Could there be a link between FMO3 and SARS-CoV-2 infection and vaccination? 

Individuals differ in their susceptibility to viral infections and genes contribute to the risk score. Less than 10% of humans infected with Mycobacterium tuberculosis develop TB, partially because of polymorphism in Tyrosine kinase (TYK2, P1104A) also responsible for severe COVID-19. Early in the pandemic, it was discovered that SARS-CoV-2 infection is dependent on the ACE2 receptor for cell entry and the serine protease TMPRSS2 for spike protein priming. ACE2 expression, indeed, influences COVID-19 risk and a rare variant located close to this gene was found to confer protection against COVID-19, possibly by decreasing ACE2 expression. Interestingly, FMO3 is one of the few genes with expression correlated to ACE2 [Sungnak et al, 2020] along with genes associated with immune functions. 

One of the characteristics of COVID-19 is the appearance of inflammatory processes, which could be leading to increased levels of TMAO. It could contribute to the hypercoagulative state in COVID-19-associated coagulopathy (CAC). SARS-Cov2 was shown to enhance TMAO-induced inflammation.  

Coronavirus disease is associated with increased risk of thrombotic events. According to recent research, low levels of FMO3 protect against thrombosis [Shih et al, 2019] while some FMO3 mutations confer higher risk [Oliveira-Filho et al, 2021]. FMO3 rs1736557 might increase the anti‐platelet efficacy of clopidogrel [Zhu et al, 2021]. Genetic risk can be mediated by gut microbiota [Gabashvili, 2020]. There are also associations with salt tolerance, wound healing, and diseases such as diabetes, renal and cardiovascular conditions increasing risk of severe COVID-19. 

Studying trimethylaminuria-like conditions might help in developing strategies for prevention and therapy of other diseases, including COVID-19.

Our COVID-19 disease and vaccines study [NCT04832932, Gabashvili, 2021] compares side-effects of vaccines and clinical course of infections (including vaccine breakthroughs) in several cohorts including MEBO and TMAU. You can help by enrolling and participating in this online survey in English or Spanish.

REFERENCES

Andreakos E, Abel L, Vinh DC, Kaja E, Drolet BA, Zhang Q, O’Farrelly C, Novelli G, Rodríguez-Gallego C, Haerynck F, Prando C. A global effort to dissect the human genetic basis of resistance to SARS-CoV-2 infection. Nature immunology. 2021 Oct 18:1-6. 

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.  

Gabashvili IS. Community-Based Phenotypic Study of Safety, Tolerability, Reactogenicity and Immunogenicity of Emergency-Use-Authorized Vaccines Against COVID-19 and Viral Shedding Potential of Post-Vaccination Infections: Protocol for an Ambispective study. medRxiv 2021.06.28.21256779; doi: https://doi.org/10.1101/2021.06.28.21256779

Liu W, Wang C, Xia Y, Xia W, Liu G, Ren C, Gu Y, Li X, Lu P. Elevated plasma trimethylamine-N-oxide levels are associated with diabetic retinopathy. Acta Diabetologica. 2021 Feb;58(2):221-9.

Janmohamed A, Dolphin CT, Phillips IR, Shephard EA. Quantification and cellular localization of expression in human skin of genes encoding flavin-containing monooxygenases and cytochromes P450. Biochemical pharmacology. 2001 Sep 15;62(6):777-86.

Oliveira-Filho AF, Medeiros PF, Velloso RN, Lima EC, Aquino IM, Nunes AB. Trimethylaminuria and Vascular Complications. Journal of the Endocrine Society. 2021 Apr;5(Supplement_1):A313-4. 

Zhu KX, Song PY, Li MP, Du YX, Ma QL, Peng LM, Chen XP. Association of FMO3 rs1736557 polymorphism with clopidogrel response in Chinese patients with coronary artery disease. European Journal of Clinical Pharmacology. 2021 Mar;77(3):359-68.

Sungnak W, Huang N, Bécavin C, Berg M, Queen R, Litvinukova M, Talavera-López C, Maatz H, Reichart D, Sampaziotis F, Worlock KB. SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes. Nature medicine. 2020 May;26(5):681-7.

Shih, D.M., Zhu, W., Schugar, R.C., Meng, Y., Jia, X., Miikeda, A., Wang, Z., Zieger, M., Lee, R., Graham, M. and Allayee, H., 2019. Genetic deficiency of Flavin-containing monooxygenase 3 (Fmo3) protects against thrombosis but has only a minor effect on plasma lipid levels—brief report. Arteriosclerosis, thrombosis, and vascular biology, 39(6), pp.1045-1054.