Abstract
Obesity is a worsening global epidemic that is regulated by the microbiota through unknown bacterial factors. We discovered a human commensal bacterium, Clostridium immunis , that treats obesity by secreting a phosphocholine-modified exopolysaccharide. Loss-and gain-of-function bacterial mutants involving the phosphocholine biosynthesis locus ( licABC ) revealed the phosphocholine moiety is critically required to protect against metabolic disease. This C. immunis exopolysaccharide acts by decreasing small-intestinal and visceral fat levels of IL-22, which results in the recruitment of beige cells specifically in visceral adipose tissue and ultimately increased energy expenditure. 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 provides immunometabolic control of obesity. More broadly, they highlight a clinically translatable strategy to increase energy expenditure and reduce visceral fat.