biostudies-literatureLu QNIDDK NIH HHSNIH HHSeadk2536https://www.ebi.ac.uk/biostudies/studies/S-EPMC12486176biostudies-literatureUnknown385(6716)Harnessing the microbiome to benefit human health requires an initial step in determining the identity and function of causative microorganisms that affect specific host physiological functions. We show a functional screen of the bacterial microbiota from mice with low intestinal immunoglobulin A (IgA) levels; we identified a Gram-negative bacterium, proposed as <i>Tomasiella immunophila</i>, that induces and degrades IgA in the mouse intestine. Mice harboring <i>T. immunophila</i> are susceptible to infections and show poor mucosal repair. <i>T. immunophila</i> is auxotrophic for the bacterial cell wall amino sugar N-acetylmuramic acid. It delivers immunoglobulin-degrading proteases into outer membrane vesicles that preferentially degrade rodent antibodies with kappa but not lambda light chains. This work indicates a role for symbionts in immunodeficiency, which might be applicable to human disease.Science (New York, N.Y.)A host-adapted auxotrophic gut symbiont induces mucosal immunodeficiency.PMC12486176F32 DK136180S10 OD023436Zhou JYStappenbeck TSSangwan NHan YNolan LSHitch TCAKarell PEBaldridge MTEspenschied STSalazar VNewhall KPLawrence DDwidar MClavel TLu QfalseA host-adapted auxotrophic gut symbiont induces mucosal immunodeficiency.Harnessing the microbiome to benefit human health requires an initial step in determining the identity and function of causative microorganisms that affect specific host physiological functions. We show a functional screen of the bacterial microbiota from mice with low intestinal immunoglobulin A (IgA) levels; we identified a Gram-negative bacterium, proposed as <i>Tomasiella immunophila</i>, that induces and degrades IgA in the mouse intestine. Mice harboring <i>T. immunophila</i> are susceptible to infections and show poor mucosal repair. <i>T. immunophila</i> is auxotrophic for the bacterial cell wall amino sugar N-acetylmuramic acid. It delivers immunoglobulin-degrading proteases into outer membrane vesicles that preferentially degrade rodent antibodies with kappa but not lambda light chains. This work indicates a role for symbionts in immunodeficiency, which might be applicable to human disease.2024-01-01T00:00:00Z2024 Sep2026-06-04T00:36:38.504Z2026-05-03T03:12:33.69ZS-EPMC124861763932590610.1126/science.adk2536