Interspecies commensal interactions have nonlinear impacts on host immunity

The impacts of individual commensal microbes on immunity and disease can differ dramatically depending on the surrounding microbial context; however, the specific bacterial combinations that dictate divergent immunological outcomes remain largely undefined. Here, we characterize an immunostimulatory Allobaculum species from an inflammatory bowel disease patient that exacerbates colitis in gnotobiotic mice. Allobaculum inversely associates with the taxonomically divergent immunostimulatory species Akkermansia muciniphila in human-microbiota-associated mice and human cohorts. Co-colonization with A. muciniphila ameliorates Allobaculum-induced intestinal epithelial cell activation and colitis in mice, whereas Allobaculum blunts the A.muciniphila-specific systemic antibody response and reprograms the immunological milieu in mesenteric lymph nodes by blocking A.muciniphila-induced dendritic cell activation and T cell expansion. These studies thus identify a pairwise reciprocal interaction between human gut bacteria that dictates divergent immunological outcomes. Furthermore, they establish a generalizable framework to define the contextual cues contributing to the “incomplete penetrance” of microbial impacts on human disease. [Display omitted] •Allobaculum isolates from ulcerative colitis patients exacerbate colitis in mice•Immunostimulatory Allo. sp. are inversely correlated with Akkermansia muciniphila•Co-colonization uniquely alters immune responses elicited by Allo. or A. muc. alone•“Epistatic” interspecies interactions have nonlinear impacts on host immunity Microbial community context can critically alter commensal-induced immune responses. Here, Rice et al. describe a reciprocal interaction between a novel colitogenic human Allobaculum species and Akkermansia muciniphila that uniquely reprograms the immune responses elicited by either microbe alone, revealing nonlinear impacts of interspecies interactions on host immunity.