A defined microbial community remodels host metabolism and pathogen resistance in Caenorhabditis elegans.

The microbiome is an important regulator of metabolism and health, yet the mechanisms by which microbial communities influence host physiological state remain incompletely understood. Here we used a defined host-microbiota model consisting of Caenorhabditis elegans and an 11-member bacterial consortium representative of its natural microbiota (DefNatMta). We investigated how this native microbial community influences host metabolism and physiology relative to the standard laboratory diet, E. coli OP50. Transcriptomic analyses revealed remodelling of host pathways associated with lipid metabolism, immunity and xenobiotic detoxification. Comparison with fasting-responsive transcriptional programmes showed that the DefNatMta response is distinct from fasting or caloric restriction. DefNatMta enhanced resistance to Staphylococcus aureus infection, and this protective effect was consistent with roles for the conserved host defence regulators PMK-1/p38 MAPK and HLH-30/TFEB. Additionally, DefNatMta reduced lipid accumulation, modified expression of lipid metabolism genes, and altered fatty acid composition, including enrichment of monomethyl branched-chain fatty acids and polyunsaturated fatty acids. Together, these findings demonstrate that a defined microbial community can induce transcriptional, metabolic and physiological remodelling in the host. Our results are consistent with microbial communities shaping host metabolic state and immune competence.