Selection and transmission of the gut microbiome alone shifts mammalian behavior

Natural selection acts on phenotypic variation, which is influenced by genetic and environmental factors including the microbiome. Whether microbiome-mediated host phenotypes can be selected and transmitted remains untested in vertebrates. Here, we first identified locomotor activity as a trait transmissible through the gut microbiome in mice. We then performed a selection experiment, where we serially transferred microbiomes from low-activity mice to independently bred germ-free mice. Over four transfer rounds, microbiome transfer significantly reduced locomotor activity. Reduced locomotion was associated with increased Lactobacilli and their metabolite indolelactate. In a test of causality, independent administration to the mouse gut of Lactobacillus johnsonii or indolelactate reduced locomotion. These findings demonstrate that selection and transmission of microbes can modulate host traits independently of selection on the mammalian genome. One Sentence SummarySerial transfer of the gut microbiome of low-activity mice to germfree recipients reproducibly transferred activity levels, revealing the microbiomes potential to impact the hosts response to selection without host genomic changes.