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Similar to other autoimmune diseases, the gut microbiome might encode disease-triggering or disease-sustaining factors.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>The gut microbiomes from IgG4-RD and SSc patients as well as healthy individuals with no recent antibiotic treatment were studied by metagenomic sequencing of stool DNA. De novo assembly-based taxonomic and functional characterization, followed by association and accessory gene set enrichment analysis, were applied to describe microbiome changes associated with both diseases.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Microbiomes of IgG4-RD and SSc patients distinctly separated from those of healthy controls: numerous opportunistic pathogenic <jats:italic>Clostridium<\/jats:italic> and typically oral <jats:italic>Streptococcus<\/jats:italic> species were significantly overabundant, while <jats:italic>Alistipes<\/jats:italic>, <jats:italic>Bacteroides<\/jats:italic>, and butyrate-producing species were depleted in the two diseases compared to healthy controls. Accessory gene content analysis in these species revealed an enrichment of Th17-activating <jats:italic>Eggerthella lenta<\/jats:italic> strains in IgG4-RD and SSc and a preferential colonization of a homocysteine-producing strain of <jats:italic>Clostridium bolteae<\/jats:italic> in SSc. Overabundance of the classical mevalonate pathway, hydroxyproline dehydratase, and fibronectin-binding protein in disease microbiomes reflects potential functional differences in host immune recognition and extracellular matrix utilization associated with fibrosis. Strikingly, the majority of species that were differentially abundant in IgG4-RD and SSc compared to controls showed the same directionality in both diseases. Compared with multiple sclerosis and rheumatoid arthritis, the gut microbiomes of IgG4-RD and SSc showed similar signatures; in contrast, the most differentially abundant taxa were not the facultative anaerobes consistently identified in inflammatory bowel diseases, suggesting the microbial signatures of IgG4-RD and SSc do not result from mucosal inflammation and decreased anaerobism.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These results provide an initial characterization of gut microbiome ecology in fibrosis-prone IgG4-RD and SSc and reveal microbial functions that offer insights into the pathophysiology of these rare diseases.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13073-021-00853-7","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T10:04:54Z","timestamp":1614593094000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Congruent microbiome signatures in fibrosis-prone autoimmune diseases: IgG4-related disease and systemic sclerosis"],"prefix":"10.1186","volume":"13","author":[{"given":"Damian R.","family":"Plichta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juhi","family":"Somani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Pichaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary S.","family":"Wallace","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana D.","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cory A.","family":"Perugino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harri","family":"L\u00e4hdesm\u00e4ki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Stone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hera","family":"Vlamakis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dinesh","family":"Khanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiv","family":"Pillai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5630-5167","authenticated-orcid":false,"given":"Ramnik J.","family":"Xavier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,28]]},"reference":[{"key":"853_CR1","doi-asserted-by":"publisher","unstructured":"Skelly AN, Sato Y, Kearney S, Honda K. 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Human patient research in the SSc cohort was approved by the Institutional Review Board of the University of Michigan Medical School (HUM00101836). Human patient research in the healthy control cohort was reviewed and approved by the Partners Human Research Committee (2015P000275). The study was approved by the Office of Research Subject Protection at the Broad Institute of MIT and Harvard. All experiments adhered to the regulations of these review boards. Study procedures were performed in compliance with all relevant ethical and federal regulations. This research conformed to the principles of the Helsinki Declaration. All study participants gave their written informed consent for sample collection and to participate in the study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"RJX is a consultant to Novartis and Nestle. DK is a consultant to Acceleron, Actelion, Amgen, Bayer, Blade Therapeutics, Boehringer Ingelheim, CSL Behring, Corbus, Cytori, Galapagos, Genentech\/Roche, GSK, Horizon, Merck, Mitsubishi Tanabe Pharma, Regeneron, Sanofi-Aventis, and United Therapeutics; CME programs: Impact PH; Stocks: Eicos Sciences, Inc.; Leadership\/Equity position -Medical lead, Scleroderma Development, CiviBioPharma\/Eicos Sciences, Inc. The remaining authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"35"}}