Mammal-microbial coevolution: mechanisms and health implications - PROJECT SUMMARY The goal of my research program is to investigate the mechanisms of mammal-microbial coevolution and its implications for host health, with a focus on codiversification—the parallel evolutionary history of host and microbial lineages. The microbiome has emerged as a key therapeutic target, and disruptions in these coevolved relationships are linked to adverse health outcomes, including immune, metabolic, and behavioral changes. However, the mechanisms underlying codiversification and the health impacts of losing vertically transmitted microbes in mammals remain unclear. As human migration and translocation increase, populations are exposed to novel microbes, making it crucial to predict host-microbial interactions in changing environments. Over the next five years, we will utilize Peromyscus spp. (deer mice) in the Arizona Sky Islands—an isolated system where mouse populations diverged similarly to major human populations—to disentangle the mechanisms of codiversification across various temporal and spatial scales. This natural experiment, combined with laboratory experiments, provides a unique model to assess how codiversification influences host phenotypes. The research will address three major knowledge gaps: (1) Identify codiversified microbial taxa and traits across body sites (skin, vaginal tract, small intestine, and feces), populations, and species; (2) Investigate mechanisms driving codiversification, specifically whether host filtering or dispersal limitation governs microbiome assembly; and (3) Assess how disruptions in codiversification affect host health by measuring changes in immune response, metabolic function, and behavior. We will generate whole-genome and metagenomic sequencing data to construct phylogenies for both host and microbial lineages and identify key microbial taxa and traits that are passed across generations. A key challenge will be distinguishing host filtering from dispersal limitations in shaping evolutionarily stable host-microbial associations. However, our comprehensive sampling design, manipulative laboratory experiments, and new bioinformatic tools provide a rigorous framework to tackle this issue. Fecal transplant experiments will offer the first description of mammalian phenotypes in response to host population- and species-level differences in microbiomes, addressing critical knowledge gaps and motivating future research. These findings have significant implications for the development of microbiome-based therapeutics tailored to specific host genotypes and ancestries, supporting a precision medicine approach.
