Interspecies commensal interactions have nonlinear impacts on host immunity

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Individual commensal microbes have varied impacts on immunity and disease, influenced by their microbial context.
• Specific bacterial combinations driving divergent immunological outcomes are not well-defined.

Purpose of the Study:

• To investigate the immunological consequences of specific bacterial interactions in the gut.
• To characterize the role of an immunostimulatory Allobaculum species in inflammatory bowel disease (IBD).

Main Methods:

• Characterization of an Allobaculum species from an IBD patient in gnotobiotic mice.
• Analysis of the inverse association between Allobaculum and Akkermansia muciniphila in mouse models and human cohorts.
• Evaluation of co-colonization effects on intestinal epithelial cell activation, colitis, antibody responses, and immune cell activity in mesenteric lymph nodes.

Main Results:

• Allobaculum exacerbated colitis in gnotobiotic mice.
• Akkermansia muciniphila co-colonization ameliorated Allobaculum-induced intestinal epithelial cell activation and colitis.
• Allobaculum impaired A. muciniphila-specific antibody responses and dendritic cell activation, while blocking T cell expansion.

Conclusions:

• A pairwise reciprocal interaction between Allobaculum and Akkermansia muciniphila dictates divergent immunological outcomes.
• This study provides a framework for understanding how microbial context influences the "incomplete penetrance" of microbial impacts on human disease.