Abstract
Abstract Specific members of the microbiota are known to modulate the immune system, which also plays an important role in regulating metabolism. Indeed, there are emerging data detailing specific bacterial species that impact multiple physiological outcomes, but the mechanisms underlying these pleiotropic effects are unclear. We previously discovered a new human commensal bacteria species, Clostridium immunis, that protects against colitis. Here, we define the host and bacterial mechanisms of action for C. immunis-mediated disease regulation. We found that C. immunis treatment decreases ILC3 numbers and function in mice and humans. Consistent with this finding, C. immunis regulates the severity of intestinal and extra-intestinal inflammatory diseases, as well as body composition in an ILC3-dependent manner. Interestingly, C. immunis influences metabolism by decreasing expression of lipid processing genes, thereby inhibiting dietary fat processing. The bioactive component of C. immunis is a secreted product and comparative genomics identified 8 C. immunis genes associated with ILC3 regulation. Collectively, we have demonstrated how a single bacterial species impacts different physiological pathways via its suppression of ILC3s. More broadly, our work reveals a microbiome-based therapy for diseases driven by pathogenic ILC3s. Supported by a Development Award from the National University of Singapore and a Graduate Student Award from the Triangle Center for Evolutionary Medicine
Published Version
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