Dietary history contributes to enterotype-like clustering and functional metagenomic content in the intestinal microbiome of wild mice.

Understanding the origins of gut microbial community structure is critical for the identification and interpretation of potential fitness-related traits for the host. The presence of community clusters characterized by differences in the abundance of signature taxa, referred to as enterotypes, is a debated concept first reported in humans and later extended to other mammalian hosts. In this study, we provide a thorough assessment of their existence in wild house mice using a panel of evaluation criteria. We identify support for two clusters that are compositionally similar to clusters identified in humans, chimpanzees, and laboratory mice, characterized by differences in Bacteroides, Robinsoniella, and unclassified genera belonging to the family Lachnospiraceae. To further evaluate these clusters, we (i) monitored community changes associated with moving mice from the natural to a laboratory environment, (ii) performed functional metagenomic sequencing, and (iii) subjected wild-caught samples to stable isotope analysis to reconstruct dietary patterns. This process reveals differences in the proportions of genes involved in carbohydrate versus protein metabolism in the functional metagenome, as well as differences in plant- versus meat-derived food sources between clusters. In conjunction with wild-caught mice quickly changing their enterotype classification upon transfer to a standard laboratory chow diet, these results provide strong evidence that dietary history contributes to the presence of enterotype-like clustering in wild mice.