Immunoglobulin-degrading commensal bacterium in wild-type B6 mice. A host-adapted auxotrophic gut symbiont induces mucosal immunodeficiency

The microbiome holds great promise as a source of novel therapeutic targets for many diseases. Mining for causative microbes that impact processes underlying disease states should utilize Koch’s postulates. Here we show a functional screen of the bacterial microbiome for mice deficient in luminal IgA; we identified a novel gram-negative bacterium, named as Tomasiella immunophila that degrades IgA both in vitro and in vivo. T. immunophila was strictly auxotrophic for the bacterial cell wall amino sugar N-acetylmuramic acid (MurNAc). T. immunophila secreted IgA-degrading enzymes exclusively onto outer membrane vesicles (OMVs) and preferentially degraded rodents’ antibodies with kappa but not lambda light chains. We propose this study uncovers a new paradigm for the role of symbionts in immunodeficiency that can ultimately be applied to human disease.