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Immunol."],"abstract":"<jats:p>The B-cell scaffold protein with ankyrin repeats (BANK1) regulates Toll-like receptor-7 (TLR7) signaling in B cells and its absence ameliorates lupus. Here, we investigated the involvement of <jats:italic>Bank1<\/jats:italic> in the gut mucosal B cell response to commensals in a murine model of lupus. In health and disease, <jats:italic>Bank1<\/jats:italic> deficiency resulted in changes in the intestinal IgA production levels that showed differential bacterial binding associated with a re-organization on the composition and structure of the gut microbiota. Furthermore, the amelioration of lupus gut pathology in mice lacking <jats:italic>Bank1<\/jats:italic> was linked to the increase of <jats:italic>Parabacteroides distasonis<\/jats:italic> that when vertically transmitted or orally administered, as emerging probiotic, reduced disease severity and repaired signs of distorted intestinal permeability. The increase of <jats:italic>P. distasonis<\/jats:italic> directly correlated with anti-inflammatory processes. <jats:italic>In vitro<\/jats:italic> stimulation either with <jats:italic>P. distasonis<\/jats:italic> or via TLR9 allowed for the differentiation of IL-10 producing B cells which, <jats:italic>in vivo<\/jats:italic>, differentially accumulated in the Peyer\u00b4s patches of <jats:italic>Bank1<\/jats:italic>-deficient lupus mice. Finally, the blood microbiome of lupus patients was found to be devoid of <jats:italic>P. distasonis<\/jats:italic>, whereas healthy controls exhibited the bacterium, thereby supporting the protective role of <jats:italic>P. distasonis<\/jats:italic> in the disease.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1586025","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T06:05:54Z","timestamp":1753077954000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Bank1 deficiency reshapes the gut microbiota of lupus mice towards an anti-inflammatory 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