Night-Restricted Feeding Improves Gut Health by Synchronizing Microbe-Driven Serotonin Rhythm and Eating Activity-Driven Body Temperature Oscillations in Growing Rabbits

Abstract

The circadian misalignment of the gut microbiota caused by unusual eating times in adult animals is related to disease development. However, whether the composition and diurnal rhythm of gut microbiota can be optimized by synchronizing the window period of eating with natural eating habits to reduce the risk of diarrhea remains unclear, especially in growing animals. In this study, 108 5-week-old weaned rabbits (nocturnal animals) were randomly subjected to daytime feeding (DF) and night-restricted feeding (NRF). At age 12 weeks, six rabbits were selected from each group, and caecum and cecal contents, as well as serum samples were collected at 4-h intervals during 24 h. Overall, NRF was found to reduce the risk of diarrhea in growing rabbits, improved the diurnal rhythm and abundance of beneficial microorganisms, along with the production of beneficial metabolites, whereas reduced the abundance of potential pathogens (Synergistes, Desulfovibrio, and Alistipes). Moreover, NRF improved diurnal rhythm of tryptophan hydroxylase isoform 1 and serotonin. Furthermore, NRF strengthened the diurnal amplitude of body core temperature, and promoted the diurnal expression of intestinal clock genes (BMAL1, CLOCK, REV-ERBα, and PER1), and genes related to the regulation of the intestinal barrier (CLAUDIN-1), and intestinal epithelial cell self-proliferation and renewal (BMI1). In vitro simulation experiments further revealed that synchronization of microbial-driven serotonin rhythm and eating activity-driven body temperature oscillations, which are important zeitgebers, could promote the diurnal expression of clock genes and CLAUDIN-1 in rabbit intestinal epithelial cells (RIEC), and enhance RIEC proliferation. This is the first study to reveal that NRF reprograms the diurnal rhythm of the gut microbiome, promotes the diurnal expression of clock genes and tight junction genes via synchronization of microbial-driven serotonin rhythm and eating activity-driven body temperature oscillations, thereby improving intestinal health and reducing the risk of diarrhea in growing rabbits. Collectively, these results provide a new perspective for the healthy feeding and management of growing animals.

Understanding the Diurnal Oscillation of the Gut Microbiota Using Microbial Culture

“…Other physiological and molecular aspects may be associated with these diurnal oscillations in the gut microbiota and should be observed in future studies. Wang et al (2021) aimed to explore the effect of different feeding patterns on intestinal health through, among other parameters, the expression of short-chain fatty acids (SCFA), intestinal tight junction proteins, clock genes, and the diurnal rhythm of microbial populations in rabbits [ 49 ]. At the beginning of the dark phase (ZT13), levels of butyric acid (SCFA) were higher in the control group when compared to the restricted food group (intervention group).…”

“…However, in the same ZT, levels of CLAUDIN-1 (intestinal tight junction proteins) and PER1 (clock gene) were significantly higher in the intervention group. In addition, there were different percentages of relative abundance in Firmicutes and Bacteroidetes phyla in ZT13; the first were cited higher in the intervention group but the second were cited lower in the same group [ 49 ]. Here, we observed different CFU/mL counting at ZT12 among the culture media, and the BA medium had the lowest count.…”

Time‐restricted eating for chronodisruption‐related chronic diseases

“…The influence of TRF on the diurnal rhythm of the expression of Abcb1a gene, which encodes for a p‐glycoprotein that mediates the transport of a variety of substances including lipids, porphyrins, and sterols, was reported in the rat intestine 155 . Additionally, night‐time RF significantly upregulated the expression of both intestinal stem cell markers, Bmi1 and Lgr5 , and also Claudin‐1 , which are important for regulating intestinal epithelial homeostasis and barrier function 156 . Microbial‐driven serotonin rhythm was shown to be an important zeitgeber for the diurnal expression of clock genes and Claudin‐1 .…”

“…155 Additionally, night-time RF significantly upregulated the expression of both intestinal stem cell markers, Bmi1 and Lgr5, and also Claudin-1, which are important for regulating intestinal epithelial homeostasis and barrier function. 156 Microbial-driven serotonin rhythm was shown to be an important zeitgeber for the diurnal expression of clock genes and Claudin-1. TRF protected mice from developing DSS-induced colitis, through reducing the abundance of colitis-related microbes, boosting the growth of beneficial, anti-inflammatory-related microbes, and increasing the SCFAs production in the gut.…”

Associations Between Disordered Microbial Metabolites and Changes of Neurotransmitters in Depressed Mice

“…Our group found that a panel consisting of four plasma neurotransmitters could effectively diagnose patients with depression from healthy controls ( Pan et al., 2018 ), and we also observed the disturbance of neurotransmitters in the hippocampus and hypothalamus of DM ( Pan et al., 2019 ; Wang et al., 2020 ; Wu et al., 2020 ; Tian et al., 2021 ). Growing pieces of evidence suggested that there were close relationships between gut microbiota and neurotransmitters ( Chen et al., 2021 ; Huang and Wu, 2021 ; Wang et al., 2021 ). Using chronic restraint stress (CRS)–induced depression model, we found the close relationships between disordered microbial metabolites and changed neurotransmitters in the hippocampus and hypothalamus of DM ( Wu et al., 2020 ; Tian et al., 2021 ).…”