Impact of type 2 immunity on small intestinal microbiota

Metabolites produced by the gut microbiota influence intestinal immunity and epithelial cell function. These molecular cues are often derived from bacteria, but here, we show that succinate generated by the commensal protist Tritrichomonas musculis (T. mu) increases goblet and Paneth cell numbers and profoundly alters the antimicrobial peptide (AMP) landscape in the distal small intestine. Succinate was sufficient to drive this epithelial remodeling, but not in mice lacking tuft cell chemosensory components required to detect this metabolite. Tuft cells respond to succinate by stimulating type 2 immunity, leading to interleukin-13-mediated epithelial and AMP expression changes. Moreover, type 2 immune activation decreases the total number of mucosa-associated microbes, including segmented filamentous bacteria (SFB), and alters the small intestinal microbiota composition. These findings demonstrate that a single metabolite produced by commensals, like T. mu, can markedly alter the antimicrobial profile of the intestine and shape host-microbiota interactions.