Genetic mapping of functional microbial traits in hybrid mice
The genetic basis of host-microbiome interactions remains largely unexplored at the functional level. Here, we use shotgun metagenomic sequencing in a panel of hybrid house mice to map host loci associated with microbial functional traits and directly compare these results to 16S rRNA gene-based taxonomic mapping in the same population. We identify 892 genome-wide and 182 study-wide significant loci linked to microbial functions, with narrower mapping intervals and fewer genes per region than previously observed for taxonomic traits, suggesting more precise genetic control.  Functional traits are substantially more heritable than taxonomic ones, supporting the hypothesis that host genetics exerts a stronger influence on microbial capabilities than on composition. In addition to confirming the importance of immune, antimicrobial, and metabolic pathways, we identify a novel set of collagen-related host genes as central hubs in host–microbe interaction networks. These findings offer new insights into the genetic architecture of microbial functionality and suggest potentially important co-evolutionary dynamics at the host-microbiome interface.