The magnitude of sex differences in host-microbe interactions are time-of-day dependent

Abstract

SUMMARYCircadian rhythms in microbial communities regulate a variety of essential homeostatic functions in the intestinal tract and distal tissues. Circadian disruption is often associated with sex-specific disease risk, but studies on circadian rhythms, the microbiome, and health outcomes primarily use male mice or collapse both sexes into one experimental condition. Here, we identify sex differences in diurnal rhythms in the intestinal microbiota, the metabolites they produce, and the expression of host genes, with more pronounced effects in females. The magnitude of these sex differences also varies by time of day, suggesting that time of collection may influence the capacity to detect sex differences in mice. Further, transitioning female mice to high-fat and low-fiber diet abolished circadian rhythms in microbiota, metabolites, and host gene expression that is entrained by a chow diet. As a result, consumption of a high-fat and low-fiber diet generated new diurnal rhythms in the microbiota and host transcriptome in females. Together, we show that circadian rhythms in the crosstalk between microbiota and their hosts are sex-specific and that diet plays an essential role in maintaining these sex differences.