Despite being the overlooked Cinderella of our senses, the impact of smell on our well-being is profound.
Tuesday, December 20, 2022
Current Trends in Deodorization
Thursday, November 17, 2022
Olfactory Signatures and COVID-19
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.
Wednesday, April 20, 2022
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.
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.
Wednesday, January 12, 2022
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
Tuesday, January 4, 2022
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.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.
Wednesday, December 1, 2021
FMO3 and COVID-19
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.
Friday, November 5, 2021
The PKU microbiome
Phenylketonuria or PKU is an inborn error of metabolism associated with a "mousy" or "musty" odor. This odor is due to a buildup of phenylalanine substances in the body. Recent study explored gut microbiome in adults with PKU and found high levels of Bifidobacterium, Bacillus, Alistipes, Clostridium, Akkermansia, and Bacteroides, while much lower levels of Lactobacillus, Porphyromonas, Frisingicoccus, Blautia, and Faecalibacterium.
REFERENCES
Mancilla VJ, Mann AE, Zhang Y, Allen MS. The Adult Phenylketonuria (PKU) Gut Microbiome. Microorganisms 2021, 9, 530.