The mouse gut microbiota responds to predator odor and predicts host behavior

In mammals, chronic stressors can alter gut microbial communities in ways that mediate host stress responses. However, the effects of acute stressors on the gut microbiota, and how these interact with host stress responses, are less well understood. Here, we show that acute exposure of wild-derived mice (Mus musculus domesticus) to predator odor altered the composition of the gut microbiota, which in turn predicted host behavior. We experimentally tested the individual and combined effects of brief (15-minute) exposure to synthetic fox fecal odor and prolonged (4-week) social isolation—a well-established chronic stress paradigm. Leveraging behavioral assays, transcriptomics of visceral adipose tissue, and analyses of 3,500 metagenome-assembled genomes (MAGs) generated from our data, we found significant effects of predator odor on host behavior, gene expression, and gut microbiota. Gut microbial communities and host gene expression profiles responded more strongly to brief predator-odor exposure than to prolonged social isolation. The relative abundances of predator odor–responsive bacterial species—including members of the Muribaculaceae and Lachnospiraceae—measured a week after a single predator-odor exposure were associated with host phenotypes assessed the following week, namely grooming and social behaviors and the expression of genes involved in anti-microbial defense, even after accounting for the effects of the stressors. Using random forest classifiers, we found that variation in gut-microbiota composition significantly predicted variation in behavior within treatment groups. These results indicate interactions between the gut microbiota and the responses of wild-derived mice to the threat of predation, and ecologically relevant acute stressor.