{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T14:07:40Z","timestamp":1791900460141,"version":"4.3.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    As one of the three mammalian gasotransmitters, hydrogen sulfide (H\n                    <jats:sub>2<\/jats:sub>\n                    S) plays a major role in maintaining physiological homeostasis. Endogenously produced H\n                    <jats:sub>2<\/jats:sub>\n                    S plays numerous beneficial roles including mediating vasodilation and conferring neuroprotection. Due to its high membrane permeability, exogenously produced H\n                    <jats:sub>2<\/jats:sub>\n                    S originating from the gut microbiota can also influence human physiology and is implicated in reducing intestinal mucosal integrity and potentiating genotoxicity and is therefore a potential target for therapeutic interventions. Gut microbial H\n                    <jats:sub>2<\/jats:sub>\n                    S production is often attributed to dissimilatory sulfate reducers such as\n                    <jats:italic>Desulfovibrio<\/jats:italic>\n                    and\n                    <jats:italic>Bilophila<\/jats:italic>\n                    species. However, an alternative source for H\n                    <jats:sub>2<\/jats:sub>\n                    S production, cysteine degradation, is present in some gut microbes, but the genes responsible for cysteine degradation have not been systematically annotated in all known gut microbes. We classify mechanisms of cysteine degradation into primary, secondary, and erroneous levels of H\n                    <jats:sub>2<\/jats:sub>\n                    S production and perform a comprehensive search for primary, secondary, and erroneous cysteine-degrading enzymes in 4,644 non-redundant bacterial genomes from the Unified Human Gastrointestinal Genome (UHGG) catalog. Of the 4,644 genomes we have putatively identified 2,046 primary, 1,951 secondary, and 5 erroneous cysteine-degrading species. We identified the presence of at least one putative cysteine-degrading bacteria in metagenomic data of 100% of 6,623 healthy subjects and the expression of cysteine-degrading genes in metatranscriptomic data of 100% of 736 samples taken from 318 individuals. Additionally, putative cysteine-degrading bacteria are more abundant than sulfate-reducing bacteria across healthy controls, IBD patients and CRC patients (\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 2.2e-16, Wilcoxon rank sum test). Although we have linked many taxa with the potential for cysteine degradation, experimental validation is required to establish the H\n                    <jats:sub>2<\/jats:sub>\n                    S production potential of the gut microbiome. Overall, this study improves our understanding of the capacity for H\n                    <jats:sub>2<\/jats:sub>\n                    S production by the human gut microbiome and may help to inform interventions to therapeutically modulate gut microbial H\n                    <jats:sub>2<\/jats:sub>\n                    S production.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2021.705583","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T19:41:40Z","timestamp":1634758900000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":135,"title":["The Capacity to Produce Hydrogen Sulfide (H2S) via Cysteine Degradation Is Ubiquitous in the Human Gut Microbiome"],"prefix":"10.3389","volume":"12","author":[{"given":"Domenick J.","family":"Braccia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofang","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai","family":"Pop","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Brantley","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1038\/s41564-017-0084-4","article-title":"Metatranscriptome of human faecal microbial communities in a cohort of adult men.","volume":"3","author":"Abu-Ali","year":"2018","journal-title":"Nat. Microbiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/s41587-020-0603-3","article-title":"A unified catalog of 204,938 reference genomes from the human gut microbiome.","volume":"39","author":"Almeida","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"4149","DOI":"10.1128\/aem.71.7.4149-4152.2005","article-title":"Identification and functional analysis of Escherichia coli cysteine desulfhydrases.","volume":"71","author":"Awano","year":"2005","journal-title":"Appl. Environ. Microbiol."},{"key":"B4","year":"2021","journal-title":"Babraham Bioinformatics - Trim Galore! [Internet]."},{"key":"B5","doi-asserted-by":"crossref","first-page":"G125","DOI":"10.1152\/ajpgi.00261.2020","article-title":"Production of hydrogen sulfide by the intestinal microbiota and epithelial cells and consequences for the colonic and rectal mucosa.","volume":"320","author":"Blachier","year":"2021","journal-title":"Am. J. Physiol.-Gastrointest Liver Physiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"448","DOI":"10.3389\/fphys.2012.00448","article-title":"Microbial pathways in colonic sulfur metabolism and links with health and disease.","volume":"3","author":"Carbonero","year":"2012","journal-title":"Front Physiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1101\/gr.126516.111","article-title":"Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma.","volume":"22","author":"Castellarin","year":"2012","journal-title":"Genome Res."},{"key":"B8","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1093\/bioinformatics\/btz848","article-title":"GTDB-Tk: a toolkit to classify genomes with the Genome Taxonomy Database.","volume":"36","author":"Chaumeil","year":"2020","journal-title":"Bioinformatics"},{"key":"B9","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/nature12820","article-title":"Diet rapidly and reproducibly alters the human gut microbiome.","volume":"505","author":"David","year":"2014","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","first-page":"3762","DOI":"10.4081\/ijas.2015.3762","article-title":"Prebiotics mitigate in vitro sulfur-containing odour generation in caecal content of pigs.","volume":"14","author":"Deng","year":"2015","journal-title":"Ital. J. Anim. Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: multiple sequence alignment with high accuracy and high throughput.","volume":"32","author":"Edgar","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"B12","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41564-018-0306-4","article-title":"Gut microbiome structure and metabolic activity in inflammatory bowel disease.","volume":"4","author":"Franzosa","year":"2019","journal-title":"Nat. Microbiol."},{"key":"B13","doi-asserted-by":"crossref","first-page":"R1479","DOI":"10.1152\/ajpregu.90566.2008","article-title":"Whole tissue hydrogen sulfide concentrations are orders of magnitude lower than presently accepted values.","volume":"295","author":"Furne","year":"2008","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/s0006-2952(01)00657-8","article-title":"Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat tissues: a specialized function of the colonic mucosa.","volume":"62","author":"Furne","year":"2001","journal-title":"Biochem. Pharmacol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1111\/j.1365-2672.1988.tb01498.x","article-title":"Occurrence of sulphate-reducing bacteria in human faeces and the relationship of dissimilatory sulphate reduction to methanogenesis in the large gut.","volume":"65","author":"Gibson","year":"1988","journal-title":"J. Appl. Bacteriol."},{"key":"B16","year":"2021","journal-title":"HMMER [Internet]."},{"key":"B17","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1128\/jb.01273-06","article-title":"Conversion of methionine to cysteine in Bacillus subtilis and its regulation.","volume":"189","author":"Hullo","year":"2007","journal-title":"J. Bacteriol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1089\/ars.2009.2919","article-title":"Hydrogen sulfide: from brain to gut.","volume":"12","author":"Kimura","year":"2009","journal-title":"Antioxid Redox Signal."},{"key":"B19","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2.","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"B20","doi-asserted-by":"crossref","first-page":"W256","DOI":"10.1093\/nar\/gkz239","article-title":"Interactive Tree Of Life (iTOL) v4: recent updates and new developments.","volume":"47","author":"Letunic","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1111\/j.1572-0241.1998.083_c.x","article-title":"Fecal hydrogen sulfide production in ulcerative colitis.","volume":"93","author":"Levine","year":"1998","journal-title":"Am. J. Gastroenterol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.chom.2015.09.008","article-title":"Inflammation, antibiotics, and diet as environmental stressors of the gut microbiome in pediatric Crohn\u2019s disease.","volume":"18","author":"Lewis","year":"2015","journal-title":"Cell Host Microbe"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2083","DOI":"10.1007\/s00726-017-2493-3","article-title":"A review of the relationship between the gut microbiota and amino acid metabolism.","volume":"49","author":"Lin","year":"2017","journal-title":"Amino Acids."},{"key":"B24","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1128\/aem.43.1.227-232.1982","article-title":"Isolation of Methanobrevibacter smithii from human feces.","volume":"43","author":"Miller","year":"1982","journal-title":"Appl. Environ. Microbiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1038\/ismej.2014.208","article-title":"Phylogenetic and environmental diversity of DsrAB-type dissimilatory (bi)sulfite reductases.","volume":"9","author":"M\u00fcller","year":"2015","journal-title":"ISME J."},{"key":"B26","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/ismej.2011.90","article-title":"Abundance and diversity of mucosa-associated hydrogenotrophic microbes in the healthy human colon.","volume":"6","author":"Nava","year":"2012","journal-title":"ISME J."},{"key":"B27","doi-asserted-by":"crossref","first-page":"S","DOI":"10.1016\/S0016-5085(18)32286-8","article-title":"Su1940 - Dietary Patterns, Sulfur Intake, and the Abundance of Sulfate-Reducing Bacteria.","volume":"154","author":"Nguyen","year":"2018","journal-title":"Gastroenterology"},{"key":"B28","first-page":"D77","article-title":"Expression Atlas update: from tissues to single cells.","volume":"48","author":"Papatheodorou","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1038\/nmeth.4468","article-title":"Accessible, curated metagenomic data through ExperimentHub.","volume":"14","author":"Pasolli","year":"2017","journal-title":"Nat. Methods"},{"key":"B30","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nmeth.4197","article-title":"Salmon provides fast and bias-aware quantification of transcript expression.","volume":"14","author":"Patro","year":"2017","journal-title":"Nat. Methods"},{"key":"B31","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1038\/sj.embor.embor914","article-title":"A genomic overview of pyridoxal-phosphate-dependent enzymes.","volume":"4","author":"Percudani","year":"2003","journal-title":"EMBO Rep."},{"key":"B32","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/s41586-019-1238-8","article-title":"The integrative human microbiome project.","volume":"569","author":"Proctor","year":"2019","journal-title":"Nature"},{"key":"B33","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/s41579-019-0213-6","article-title":"Microbial genes and pathways in inflammatory bowel disease.","volume":"17","author":"Schirmer","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1126\/science.1209855","article-title":"H2S: a universal defense against antibiotics in bacteria.","volume":"334","author":"Shatalin","year":"2011","journal-title":"Science"},{"key":"B35","doi-asserted-by":"publisher","first-page":"100328","DOI":"10.1016\/j.sbsr.2020.100328","article-title":"Sensor of transdermal biomarkers for blood perfusion monitoring.","volume":"28","author":"Shekarriz","year":"2020","journal-title":"Sens Bio-Sens Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1099\/mic.0.000337","article-title":"Transcription factor DecR (YbaO) controls detoxification of L-cysteine in Escherichia coli.","volume":"162","author":"Shimada","year":"2016","journal-title":"Microbiology"},{"key":"B37","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1080\/01635589509514417","article-title":"Does digestibility of meat protein help explain large bowel cancer risk?","volume":"24","author":"Silvester","year":"1995","journal-title":"Nutr. Cancer"},{"key":"B38","year":"2021","journal-title":"SRA-Tools - NCBI [Internet]."},{"key":"B39","doi-asserted-by":"crossref","first-page":"G1028","DOI":"10.1152\/ajpgi.1997.272.5.G1028","article-title":"Insights into human colonic physiology obtained from the study of flatus composition.","volume":"272","author":"Suarez","year":"1997","journal-title":"Am. J. Physiol.-Gastrointest Liver Physiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"2992","DOI":"10.1099\/mic.0.051813-0","article-title":"Identification of an l-methionine \u03b3-lyase involved in the production of hydrogen sulfide from l-cysteine in Fusobacterium nucleatum subsp. nucleatum ATCC 25586.","volume":"157","author":"Suwabe","year":"2011","journal-title":"Microbiology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"5972","DOI":"10.1099\/ijsem.0.004213","article-title":"Proposal to reclassify the proteobacterial classes Deltaproteobacteria and Oligoflexia, and the phylum Thermodesulfobacteria into four phyla reflecting major functional capabilities.","volume":"70","author":"Waite","year":"2020","journal-title":"Int. J. Syst. Evol. Microbiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1089\/ars.2009.2938","article-title":"Hydrogen sulfide: the third gasotransmitter in biology and medicine.","volume":"12","author":"Wang","year":"2009","journal-title":"Antioxid Redox Signal."},{"key":"B43","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1152\/physrev.00017.2011","article-title":"Physiological implications of hydrogen sulfide: a whiff exploration that blossomed.","volume":"92","author":"Wang","year":"2012","journal-title":"Physiol. Rev."},{"key":"B44","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1002\/wics.147","article-title":"ggplot2.","volume":"3","author":"Wickham","year":"2011","journal-title":"WIREs Comput. Stat."},{"key":"B45","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1186\/s13059-019-1891-0","article-title":"Improved metagenomic analysis with Kraken 2.","volume":"20","author":"Wood","year":"2019","journal-title":"Genome Biol."},{"key":"B46","first-page":"510","article-title":"Modulation of colonic hydrogen sulfide production by diet and mesalazine utilizing a novel gas-profiling technology.","volume":"9","author":"Yao","year":"2018","journal-title":"Gut Microbes."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.705583\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,11]],"date-time":"2023-11-11T07:50:51Z","timestamp":1699689051000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.705583\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,20]]},"references-count":46,"alternative-id":["10.3389\/fmicb.2021.705583"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2021.705583","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.03.24.436781","asserted-by":"object"}]},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,20]]},"article-number":"705583"}}