The importance of meal timing for maintenance of daily rhythms in the gut transcriptome and microbiota.

Gut function exhibits 24 h (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 24 h colonic landscape using an interval feeding paradigm, whereby food intake was partitioned equally across the 24 h day. RNAseq analysis revealed that the IEC intrinsic clock persists in the absence of diurnal feeding rhythms; however, a subset of key transcripts loses rhythmicity, demonstrating that cell extrinsic temporal cues contribute significantly to the maintenance of the rhythmic gut transcriptome. Furthermore, interval-fed mice demonstrated a 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 the maintenance of rhythmic processes within the gut, with implications for metabolic and immune health.