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Significant morbidity and mortality are caused by immune dysregulation complications (CVIDid), which affect around one-third of CVID patients and have a poorly understood etiology. Here, we investigate the hypothesis that gut microbial dysbiosis contributes to the inflammation underlying CVIDid.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Bacterial invasion of colonic crypts was observed in CVID (3\/15) and X-linked agammaglobulinemia (XLA, 1\/3), but not in healthy control (HC, 0\/9) biopsies. Fecal gut microbiota was characterized using 16S rRNA-targeted amplicon sequencing. Increased bacterial load, decreased alpha diversity and distinct beta diversity were observed in CVIDid (<jats:italic>n<\/jats:italic>\u2009=\u200942) compared to HC (<jats:italic>n<\/jats:italic>\u2009=\u200948), and similar results were seen in CVID with IgA deficiency (<jats:italic>n<\/jats:italic>\u2009=\u200940) compared to HC. CVIDid and CVID-IgA showed enrichment of the genus <jats:italic>Enterococcus<\/jats:italic>, and in vitro studies confirmed the inflammatory potential of <jats:italic>Enterococcus gallinarum<\/jats:italic> and <jats:italic>Enterococcus hirae<\/jats:italic> in patient monocytes. <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>This study further supports the hypothesis that a dysregulated gut microbiota, with IgA deficiency as an important driving factor, contributes to systemic inflammation in primary antibody deficiency, and introduces enterococci as potential pathobionts in CVIDid.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s40168-024-01982-y","type":"journal-article","created":{"date-parts":[[2025,1,16]],"date-time":"2025-01-16T13:46:00Z","timestamp":1737035160000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Gut microbial dysbiosis, IgA, and Enterococcus in common variable immunodeficiency with immune dysregulation"],"prefix":"10.1186","volume":"13","author":[{"given":"Roos-Marijn","family":"Berbers","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda L.","family":"Paganelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joris M.","family":"van Montfrans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline M.","family":"Ellerbroek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco C.","family":"Viveen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malbert R. 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Written informed consent was obtained from all patients and controls according to the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"PH reports research grants and personal fees from Shire\/Takeda and CSL Behring. VD reports research grants and consulting fees from Shire\/Takeda, Griffols, ACtelion, Novartis and CSL Behring. JM reports personal fees from Shire\/Takeda. AvdV reports personal fees from Lamepro B.V.. HL reports research grants from Shire\/Takeda. All other authors report no potential conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"12"}}