Dietary fat disrupts a commensal-host lipid network that promotes metabolic health.

The microbiota influences metabolic health; however, few specific microbial molecules and mechanisms have been identified. We isolated a Turicibacter strain from a community of spore-forming bacteria that promotes leanness in mice. Human metagenomic analysis demonstrates reduced Turicibacter abundance in individuals with obesity. Similarly, a high-fat diet reduces Turicibacter colonization, preventing its weight-suppressive effects, which can be overcome with continuous Turicibacter supplementation. Ceramides accumulate during a high-fat diet and promote weight gain. Transcriptomics and lipidomics reveal that the spore-forming community and Turicibacter suppress host ceramides. Turicibacter produces unique lipids, which are reduced during a high-fat diet. These lipids can be transferred to host epithelial cells, reduce ceramide production, and decrease fat uptake. Treatment of animals with purified Turicibacter lipids prevents obesity, demonstrating that bacterial lipids can promote host metabolic health. These data identify a lipid metabolic circuit between bacteria and host that is disrupted by diet and can be targeted therapeutically.