Symbiotic microbial communities can affect the health and fitness of the host. Recent studies in humans and mouse models have demonstrated previously unknown roles for the gut microbiota in mammalian digestion, immunity, behavior, and development. These findings suggest that the compositional variation in gut microbiotas may play a fundamental role in host biology. However, the determinants and implications of the gut microbiota in natural populations of mammals are less well understood. My dissertation aims to identify genetic and environmental factors shaping variation in the gut microbiota and to understand the role of gut microbiota in mammalian biology. First, I reviewed studies over the last decade that show links between variation in symbiotic microbiota and variation in host phenotype in natural populations of mammals to motivate the work. Next, I found obesity-associated gut microbial composition tend to be more prevalent in humans living in colder environments consistent with the ecological pattern known as Bergmann’s rule. The results suggest a link between the gut microbiota and climatic adaptation. To further investigate whether the pattern observed in humans is general, I conducted a series of studies where I combined field observations and laboratory experiments to investigate the determinants of the gut microbiota and their roles in environmental adaptation using natural populations of house mice (Mus musculus) as a model system. I have characterized the gut microbiota of wild house mice using 16S amplicon sequencing within individuals’ gastrointestinal tract and between individuals’ cecum across two altitudinal and three latitudinal transects across the Americas. Microbiotas of the lower gastrointestinal tract showed greater individual differences compared to the upper gastrointestinal tract. The individual differences in the cecal microbiota were explained by differences in host genetic distance independent of geographic distance. Several gene-bacteria associations were identified from a microbiome genome-wide association study (mGWAS) using exome sequences. The results from the altitudinal and latitudinal transects suggest that differences in partial pressure of oxygen and host body mass may cause changes in gut microbiota. Beneficial functions of the gut microbiota regulating blood pressure at high altitudes and facilitating energy harvest at high latitudes were proposed. Many of the findings here have been replicated in other mammalian systems, including humans. Together, the results suggest general mechanisms governing the assembly and function of the mammalian gut microbiota.