Disturbed rhythmicity of intestinal hydrogen peroxide alters gut microbial oscillations in BMAL1-deficient monkeys

Yunpeng Yang; Peijun Yu; Yong Lu; Changshan Gao; Qiang Sun

doi:10.1016/j.celrep.2023.112183

Disturbed rhythmicity of intestinal hydrogen peroxide alters gut microbial oscillations in BMAL1-deficient monkeys

Cell Rep. 2023 Mar 28;42(3):112183. doi: 10.1016/j.celrep.2023.112183. Epub 2023 Feb 28.

Authors

Yunpeng Yang¹, Peijun Yu², Yong Lu³, Changshan Gao³, Qiang Sun⁴

Affiliations

¹ Institute of Neuroscience, CAS Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, P.R. China; Institute of Comparative Medicine, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, P.R. China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, P.R. China. Electronic address: ypyang@yzu.edu.cn.
² Institute of Neuroscience, CAS Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, P.R. China; University of Chinese Academy of Sciences, Beijing 100049, P.R. China.
³ Institute of Neuroscience, CAS Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, P.R. China.
⁴ Institute of Neuroscience, CAS Key Laboratory of Primate Neurobiology, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, P.R. China. Electronic address: qsun@ion.ac.cn.

PMID: 36857177
DOI: 10.1016/j.celrep.2023.112183

Abstract

Circadian oscillation of gut microbiota exerts significant influence on host physiology, but the host factors that sustain microbial oscillations are rarely reported. We compared the gut microbiome and metabolome of wild-type and BMAL1-deficient cynomolgus monkeys during a diurnal cycle by performing 16S rRNA sequencing and untargeted fecal metabolomics and uncovered the influence of intestinal H₂O₂ on microbial compositions. Ablation of BMAL1 induced expansion of Bacteroidota at midnight and altered microbial oscillations. Some important fecal metabolites changed significantly, and we investigated their correlations with microbes. Further analyses revealed that disturbed rhythmicity of NOX1-derived intestinal H₂O₂ was responsible for the altered microbial oscillations in BMAL1-deficient monkeys. Mechanistic studies showed that BMAL1 transactivated NOX1 via binding to the E1-E2 site in its promoter. Notably, BMAL1-dependent activation of NOX1 was conserved in cynomolgus monkeys and humans. Our study demonstrates the importance of intestine clock-controlled H₂O₂ rhythmicity on the rhythmic oscillation of gut microbiota.

Keywords: BMAL1-deficient cynomolgus monkeys; BMAL1-dependent activation of NOX1; CP: Microbiology; H(2)O(2) rhythmicity; circadian oscillation; fecal metabolites; gut microbiota.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ARNTL Transcription Factors / genetics
ARNTL Transcription Factors / metabolism
Animals
Circadian Rhythm* / physiology
Gastrointestinal Microbiome* / physiology
Humans
Hydrogen Peroxide / pharmacology
Macaca fascicularis
RNA, Ribosomal, 16S

Substances

ARNTL Transcription Factors
Hydrogen Peroxide
RNA, Ribosomal, 16S
BMAL1 protein, human
NOX1 protein, human