Bank1 deficiency reshapes the gut microbiota of lupus mice towards an anti-inflammatory composition

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 <i>Bank1</i> in the gut mucosal B cell response to commensals in a murine model of lupus. In health and disease, <i>Bank1</i> 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 <i>Bank1</i> was linked to the increase of <i>Parabacteroides distasonis</i> that when vertically transmitted or orally administered, as emerging probiotic, reduced disease severity and repaired signs of distorted intestinal permeability. The increase of <i>P. distasonis</i> directly correlated with anti-inflammatory processes. <i>In vitro</i> stimulation either with <i>P. distasonis</i> or via TLR9 allowed for the differentiation of IL-10 producing B cells which, <i>in vivo</i>, differentially accumulated in the Peyer´s patches of <i>Bank1</i>-deficient lupus mice. Finally, the blood microbiome of lupus patients was found to be devoid of <i>P. distasonis</i>, whereas healthy controls exhibited the bacterium, thereby supporting the protective role of <i>P. distasonis</i> in the disease.