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

Qiang-Jun Wang,Mei-Zhi Wang,Ming-Yong Li,Shi-Xia Geng,Peng Liu,Man Liu,Lei An,Yao Guo,Lei Zhang,Zhong-Ying Liu,Ke-Hao Zhang,Chun-Hua Shan,Jian-Hui Tian,Zhong-Hong Wu,Meng-Qi Zhu,Qiong-Yu Jin

doi:10.3389/fcimb.2021.771088

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.

Highlights

Unhealthy adult lifestyles that include shift work, nighttime social activities and jet lag are becoming more prevalent, and associated health problems have become more prominent (Parsons et al, 2015; Koshy et al, 2019)
The cumulative risk of diarrhea was significantly lower in the NRF group after day 68 (Figures 1C, D; p < 0.05). These results indicate that NRF is consistent with nocturnal feeding habits in growing rabbits, which is more conducive to healthy breeding
Numerous studies have demonstrated that microbial-driven serotonin and body temperature oscillation, as important zeitgebers, participate in the regulation of the clock genes expression in peripheral tissues (Buhr et al, 2010; Leone et al, 2015; Luzader et al, 2018)

Summary

Introduction

Unhealthy adult lifestyles that include shift work, nighttime social activities and jet lag are becoming more prevalent, and associated health problems have become more prominent (Parsons et al, 2015; Koshy et al, 2019). Epidemiological investigations have determined that unhealthy lifestyle-promoted metabolic syndromes and intestinal inflammatory diseases result in heavy global economic burden (Bishehsari et al, 2020). In recent years, unhealthy lifestyles causing disturbances in the diurnal rhythm of intestinal microorganisms have become the focus of research (Asher and Sassone-Corsi, 2015; Murakami and Tognini, 2019; Bishehsari et al, 2020). Selecting growing animal models to study the interference of mistimed eating on intestinal microbiological diurnal rhythm is of great significance to fill knowledge gaps regarding the impact of irregular lifestyle on the health of children and growing animals

Methods

Results

Conclusion