Diurnal feeding behaviour drives 24h rhythms within intestinal epithelial cells and the gut microbiome

Gut function exhibits 24h (circadian) rhythmicity, in part driven by intrinsic clocks within intestinal epithelial cells (IECs). The gut microbiome exhibits 24h rhythms in composition and function, which are important for maintenance of metabolic and immune health. 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 cell intrinsic clock persists in the absence of diurnal feeding rhythms, however a subset of transcripts lose rhythmicity, demonstrating that feeding driven cell extrinsic temporal cues contribute significantly to maintenance of the rhythmic gut transcriptome. Interval fed mice lost rhythmicity in secretory IgA and within the microbiota and microbial derived short chain fatty acids. 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.肠道功能呈现24小时昼夜节律（circadian rhythmicity），其调控部分源于肠上皮细胞（intestinal epithelial cells，IECs）内的固有生物钟。肠道微生物组在组成与功能层面均表现出24小时节律，这对维持代谢与免疫健康至关重要。本研究采用间歇性进食范式，即将24小时内的食物摄取均匀分配，探究了进食行为对结肠昼夜节律特征的影响。RNA测序（RNAseq）分析结果显示，即便缺乏昼夜进食节律，肠上皮细胞的固有生物钟仍可维持，但部分转录本的节律性消失，这表明进食介导的细胞外时间信号对维持肠道节律性转录组具有重要贡献。间歇性进食的小鼠，其分泌型免疫球蛋白A（secretory IgA，sIgA）、肠道微生物组以及微生物衍生的短链脂肪酸均丧失了节律性。本研究凸显了进食行为的昼夜节律对维持肠道内节律性进程的关键作用，其研究结果对代谢与免疫健康具有重要指导意义。