The keystone gut species boosts gut microbial biomass and voluntary physical activity in mice.

The gut bacteria of the family are consistently associated with metabolic health, but their role in promoting host health is not fully understood. Here, we explored the effect of amendment on voluntary physical activity and the gut microbiome. We inoculated male and female germ-free mice with an obese human donor microbiota together with live or heat-killed for 28 days and measured physical activity in respirometry cages. Compared to heat-killed, the live- treatment resulted in reduced feed efficiency and higher levels of physical activity, with significantly greater distance traveled for males and higher levels of small movements and resting metabolic rate in females. Sex-specific effects of treatment may be in part attributable to different housing conditions for males and females. Amendment with live boosted gut microbial biomass in both sexes, immobilizing dietary carbon in the microbiome, and mice with high levels of lose more energy in stool. Live also reduced within and between-host gut microbial diversity. Overall, our results showed that acts as a keystone species: despite low relative abundance, it has a large impact on its ecosystem, from the microbiome to host energy homeostasis.IMPORTANCEThe composition of the human gut microbiome is associated with human health. Within the human gut microbiome, the relative abundance of the bacterial family has been shown to correlate with metabolic health and a lean body type. The mechanisms underpinning this effect remain unclear. Here, we show that live influences host physical activity and metabolic energy expenditure, accompanied by changes in murine metabolism and the gut microbial community in a sex-dependent manner in comparison to heat-killed . Importantly, live boosts the biomass of the microbiome in the gut, and a higher level of is associated with greater loss of energy in stool. These observations indicate that modulation of activity levels and changes to the microbiome are ways in which the can influence host energy homeostasis and health.