Determining the forces that shape diversity in host-associated bacterial communities is critical to understanding the evolution and maintenance of metaorganisms. To gain deeper understanding of the role of host genetics in shaping gut microbial traits, we employed a powerful genetic mapping approach using inbred lines derived from the hybrid zone of two incipient house mouse species. Furthermore, we uniquely performed our analysis on microbial traits measured at the gut mucosal interface, which is in more direct contact with host cells and the immune system. Several mucosa-associated bacterial taxa have high heritability estimates, and interestingly, 16S rRNA transcript-based heritability estimates are positively correlated with cospeciation rate estimates. Genome-wide association mapping identifies 428 loci influencing 120 taxa, with narrow genomic intervals pinpointing promising candidate genes and pathways. Importantly, we identified an enrichment of candidate genes associated with several human diseases, including inflammatory bowel disease, and functional categories including innate immunity and G-protein-coupled receptors. These results highlight key features of the genetic architecture of mammalian host-microbe interactions and how they diverge as new species form.

Two bacterial strains, KH365_2T and KH569_7, were isolated from the cecum contents of wild-derived house mice. The strains were characterized as Gram-negative, rod-shaped, strictly anaerobic, and non-motile. Phylogenetic analysis based on 16S rRNA gene sequences revealed that both strains were most closely related to Bacteroides uniformis ATCC 8492T. Whole genome sequences of KH365_2T and KH569_7 strains have a DNA G + C content of 46.02% and 46.03% mol, respectively. Most morphological and biochemical characteristics did not differ between the newly isolated strains and classified Bacteroides strains. However, the average nucleotide identity (ANI) and dDNA–DNA hybridization (dDDH) values clearly distinguished the two strains from described members of the genus Bacteroides. Here, we present the phylogeny, morphology, and physiology of a novel species of the genus Bacteroides and propose the name Bacteroides muris sp. nov., with KH365_2T (DSM 114231T = CCUG 76277T) as type strain.

The breadth of phenotypes influenced by the gut microbiome in multicellular hosts has attracted the keen and renewed interest of evolutionary biologists. Comparative studies suggest that coevolutionary processes may occur as hosts and their associated microbes (i.e., holobionts) diverge. The majority of studies to date however lack information beyond that of 16S rRNA gene profiling, and thus fail to capture potential underlying genomic changes among microbes. In this study, we conducted a comparative genomic analysis of 19 newly sampled Bacteroides acidifaciens isolates derived from the eastern and western house mouse subspecies, Mus musculus musculus and M. m. domesticus. Through a panel of genome-wide association (GWAS) analyses applied to pangenomic content, structural gene rearrangements, and SNPs, we reveal several candidates for adaptation to the host subspecies environment. The proportion of significant loci in each respective category is small, indicating low levels of differentiation according host subspecies. However, consistent signal is observed for genes involved in processes such as carbohydrate acquisition/utilization (SusD/RagB, amyA and amyS) and de novo purine nucleotide biosynthesis (purD), which serve as promising candidates for future experimental investigation in the house mouse as a model of holobiont evolution.