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 (α1^KI-CD89^tg mice), the quantity of deglycosylated IgA1 correlated with the relative abundance of A. muciniphila at various sites in the intestinal lumen.

微生物组可以调节免疫反应，对人类健康具有重要影响，但其在获得性自身免疫性疾病中的潜在因果作用仍有待确定。现在，James Gleeson、Renato Monteiro 及其同事报告了肠道微生物失调可能导致 IgA 肾病 (IgAN) 发病机制的机制。

由于肠壁管腔侧的粘蛋白层含有与 IgA1 铰链区相似的 O 连接聚糖糖蛋白，研究人员研究了粘蛋白降解细菌是否可以改变 IgA1 的糖基化。他们表明A. muciniphila可以在体外使人 IgA1 去糖基化。此外，在表达人 IgA1 和 Fcα 受体 I 的小鼠（α1 ^KI -CD89 ^tg小鼠）中，去糖基化 IgA1 的数量与肠腔不同部位A. muciniphila的相对丰度相关。