The microbiome can modulate immune responses and has an important effect on human health, but its potential causal role in acquired autoimmune diseases remains to be determined. Now, James Gleeson, Renato Monteiro and colleagues report a mechanism by which gut microbial dysbiosis could contribute to the pathogenesis of IgA nephropathy (IgAN).

As the mucin layer on the luminal side of the gut wall contains glycoproteins with O-linked glycans similar to those found in the hinge region of IgA1, the researchers investigated whether mucin-degrading bacteria could modify the glycosylation of IgA1. They show that A. muciniphila can deglycosylate human IgA1 in vitro. Furthermore, in mice that expressed human IgA1 and Fcα receptor I (α1KI-CD89tg mice), the quantity of deglycosylated IgA1 correlated with the relative abundance of A. muciniphila at various sites in the intestinal lumen.