Selection of gut microbiome in mice

Natural selection targets phenotypic variation that is determined by genetic and environmental factors, including the microbiome. Whether gut microbiomes can be selected to drive mammalian host traits is unknown. Here, we first characterized traits transmissible from two mouse stains to a third germfree strain and identified activity as highly microbiome-transmissible. We then serially transferred microbiomes from low-activity mice to five cohorts of separately bred germfree mice. Over three rounds of transfer, microbiome selection significantly reduced host activity. Greater levels of Lactobacilli and their metabolite indolelactate were associated with reduced activity. Administration of Lactobacillus johnsonii or indolelactate to the gut also both reduced activity. Our results show selection on microbiome diversity and metabolism is sufficient to drive adaptive host traits independently of changes to the mammalian genome.