Meal timing is a critical factor for maintenance of gut homeostasis around the clock

Gut function exhibits 24 hour (circadian) rhythmicity, in part driven by intrinsic clocks within intestinal epithelial cells (IECs). The gut microbiome also demonstrates circadian rhythms in composition and function, important for maintenance of metabolic, immune and gut health. Here, we determined the influence of feeding behaviour on the colonic circadian landscape using an interval feeding paradigm, whereby food intake was partitioned equally across the 24h day. RNAseq analysis revealed that the IEC intrinsic clock persists in the absence of diurnal feeding rhythms, however a subset of key transcripts lose rhythmicity, demonstrating that cell extrinsic temporal cues contribute significantly to maintenance of the rhythmic gut transcriptome. Furthermore, interval fed mice demonstrated striking loss of rhythms in secretory IgA, a critical regulator of the temporal landscape of the gut microbiome. In keeping, rhythmicity within the microbiota and microbial derived short chain fatty acids was significantly diminished. This work highlights the importance of daily rhythms in feeding behaviour for maintenance of rhythmic processes within the gut, with implications for metabolic and immune health.