High-resolution genetic mapping of the mucosa-associated gut microbiome in hybrid mice provides novel insight on the impact of host genetics

Determining the forces that shape diversity in host-associated bacterial communities is critical to understanding the evolution and maintenance of meta-organisms. To gain novel insight on the genetics of gut microbial traits, we employed a powerful approach using inbred lines derived from the hybrid zone of two incipient house mouse species and uniquely investigated the microbiome at the gut mucosal interface. We identify a high number of mucosa-associated bacterial taxa with significant heritability estimates, particularly for 16S rRNA transcript-based traits. Interestingly, heritability estimates also positively correlate with cospeciation rate estimates. Association mapping identifies 443 loci influencing 123 taxa, whose narrow genomic intervals enable promising individual candidate genes and pathways to be pinpointed. These results indicate a unique genetic architecture for cospeciating taxa, a clear enrichment for several classes of human disease, including inflammatory bowel disease, and identify important functional categories including innate immunity and G-protein-coupled receptors, whose role in host-microbe interactions diverge as new species form.