Summary scheme for IgA–MAFF axis in the colon. Optimal in vivo metabolic capacity of B. theta requires IgA and MAFF. (1) IgA binds to B. theta via glycan–glycan interactions (IgA-glycan and LPS) and enhances the association of the bacteria with host mucus and/or diet-derived polysaccharide. (2) Mucus-associated B. theta induces MAFF system expression dependent on interaction with Firmicutes members such as Clostridiales and enhances the metabolic activity of B. theta. (3) Metabolically active B. theta induces the expansion of Clostridiales members, altering the composition of the gut microbial community. (4) The MAFF-induced microbiota rich in Clostridiales enhances proliferation and regeneration of colonic epithelial cells during DSS colitis. MAFF in B. vulgatus shows similar effects. Mucus-specific MAFF expression was also observed in human colon biopsies, suggesting that the MAFF system is involved in the maintenance of colonic homeostasis in both mice and humans.