Natural genetic variation drives microbiome selection in the Caenorhabditis elegans gut

Host genetic landscapes can shape microbiome assembly in the animal gut by contributing to the establishment of distinct physiological environments. However, the genetic determinants contributing to the stability and variation of these microbiome types remain largely undefined. Here, we use the free-living nematode Caenorhabditis elegans to identify natural genetic variation among wild strains of C. elegans strains that drives assembly of distinct microbiomes. To achieve this, we first established a diverse model microbiome that represents the phylogenetic and functional diversity naturally found in the C. elegans microbiome. Using this community, we show that C. elegans utilizes immune, xenobiotic and metabolic signaling pathways to favor the assembly of different microbiome types. Variations in these pathways were associated with the enrichment for specific commensals, including the Alphaproteobacteria Ochrobactrum. Using RNAi and mutant strains, we showed that host selection for Ochrobactrum is mediated specifically by host insulin signaling pathways. Ochrobactrum recruitment is blunted in the absence of daf-2/IGFR and requires the insulin signaling transcription factors daf-16/FOXO and pqm-1/SALL2. Further, the ability of C. elegans to enrich for Ochrobactrum is correlated positively with host outcomes, as animals that develop faster are larger and have higher gut Ochrobactrum colonization as adults. These results highlight a new role for the highly conserved insulin signaling pathways in the regulation of microbiome composition in C. elegans.