2. Academic Validation
  3. Caloric restriction remodels the hepatic chromatin landscape and bile acid metabolism by modulating the gut microbiota

Caloric restriction remodels the hepatic chromatin landscape and bile acid metabolism by modulating the gut microbiota

  • Genome Biol. 2023 Apr 30;24(1):98. doi: 10.1186/s13059-023-02938-5.
Yun Fan # 1 2 3,  Hong Qian # 1 2,  Meijia Zhang 2 3,  Chengzhe Tao 1 2,  Zhi Li 1 2,  Wenkai Yan 1 2,  Yuna Huang 1 2,  Yan Zhang 1 2,  Qiaoqiao Xu 1 2,  Xinru Wang 1 2,  Paul A Wade 4,  Yankai Xia 1 2,  Yufeng Qin 5 6,  Chuncheng Lu 7 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
  • 2 Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
  • 3 Department of Microbes and Infection, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
  • 4 Eukaryotic Transcriptional Regulation Group, Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA.
  • 5 Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. qiny@njmu.edu.cn.
  • 6 Department of Microbes and Infection, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. qiny@njmu.edu.cn.
  • 7 State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. chunchenglu@njmu.edu.cn.
  • 8 Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China. chunchenglu@njmu.edu.cn.
  • # Contributed equally.
PMID: 37122023 DOI: 10.1186/s13059-023-02938-5
Abstract

Background: Caloric restriction (CR) has been known to promote health by reprogramming metabolism, yet little is known about how the epigenome and microbiome respond during metabolic adaptation to CR.

Results: We investigate chromatin modifications, gene expression, as well as alterations in microbiota in a CR mouse model. Collectively, short-term CR leads to altered gut microbial diversity and bile acid metabolism, improving energy expenditure. CR remodels the hepatic enhancer landscape at genomic loci that are enriched for binding sites for signal-responsive transcription factors, including HNF4α. These alterations reflect a dramatic reprogramming of the liver transcriptional network, including genes involved in bile acid metabolism. Transferring CR gut microbiota into mice fed with an obesogenic diet recapitulates the features of CR-related bile acid metabolism along with attenuated fatty liver.

Conclusions: These findings suggest that CR-induced microbiota shapes the hepatic epigenome followed by altered expression of genes responsible for bile acid metabolism.

Keywords

Bile acid metabolism; Caloric restriction; Gut microbiota; Hepatic epigenome; Metabolic adaptation.

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