A commensal-derived sugar protects against metabolic disease

Abstract

SUMMARYObesity is a worsening global epidemic that is regulated by the microbiota through unknown bacterial factors. We discovered a human-derived commensal bacterium,Clostridium immunis, that protects against metabolic disease by secreting a phosphocholine-modified exopolysaccharide. Genetic interruption of the phosphocholine biosynthesis locus (licABC) results in a functionally inactive exopolysaccharide, which demonstrates the critical requirement for this phosphocholine moiety. ThisC. immunisexopolysaccharide acts via group 3 innate lymphoid cells and modulating IL-22 levels, which results in a reduction in serum triglycerides, body weight, and visceral adiposity. Importantly, phosphocholine biosynthesis genes are less abundant in humans with obesity or hypertriglyceridemia, findings that suggest the role of bacterial phosphocholine is conserved across mice and humans. These results define a bacterial molecule—and its key structural motif—that regulates host metabolism. More broadly, they highlight how small molecules, such as phosphocholine, may help fine-tune microbiome– immune–metabolism interactions.