Secretory IgM regulates gut microbiota homeostasis and metabolism

The coating of microbiota by secretory immunoglobulins (sIgs) determines which bacteria colonize the gut and influences bacterial metabolism. Previous work has identified sIgA and sIgT as mediators of gut homeostasis. However, sIgM coats a large proportion of the gut microbiota in humans and teleost fish, thus suggesting a conserved role of sIgM in microbiota homeostasis. Here, to investigate this hypothesis, we used the teleost rainbow trout as a model system. Depletion of IgM from trout resulted in severe microbiota-dependent gut tissue damage, body weight loss, bacterial translocation and gut dysbiosis. IgM depletion led also to alterations in microbiota-derived metabolites, including short-chain fatty acids and essential amino acids. Supporting a protective role for sIgM in the gut, high mortality of IgM-depleted fish occurred in an experimental colitis model as a result of severe systemic bacteraemia and septic shock. Our findings uncover sIgM as a previously unrecognized regulator of microbiota homeostasis and metabolism.