The intestinal microbiota programs diurnal rhythms in host metabolism through histone deacetylase 3
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Abstract
Microbial entrainment of metabolism: The metabolism of mammals is synchronized to daily cycles relating to sleep and mealtimes. It is not surprising that the gut microbiota, which aids in digestion, should also display daily cycling. Kuang et al. found that the gut microbiota can mediate daily cycles epigenetically (see the Perspective by Bishehsari and Keshavarzian). The microbiota induces rhythmic expression of histone deacetylase 3 (HDAC3) in epithelial cells of the small intestine, but not those of the colon. HDAC3 expression drives oscillations in intestinal metabolic gene expression, especially for nutrient transport and lipid metabolism. HDAC3 also directly activates estrogen-related receptor α, which promotes lipid absorption. Consequently, mice that lack a gut microbiota lack daily regulation of their metabolism and become obese on high-fat chow. Disruption of HDAC3 cycling could be an explanation for human obesity associated with antibiotic damage to the microbiota and with sleep disruption caused by jet lag and nighttime working. Science , this issue p. 1428 ; see also p. 1379
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- Authors
- Kuang, Z., Wang, Y., Li, Y., Ye, C., Ruhn, K. A., Behrendt, C. L., Olson, E. N., & Hooper, L. V.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Hooper, Lora V.
- ORCID
- Venue
- Science
- Published
- 2019-09-27
- Volume
- 365
- Issue
- 6460
- Pages
- 1428-1434
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7158748
- OpenAlex
- W2975185045
- Cited by
- 330
- References
- 41
- Citations by year
- 2026: 40 · 2025: 40 · 2024: 50 · 2023: 40 · 2022: 54 · 2021: 50 · 2020: 50 · 2019: 5 · 2014: 1
- FWCI
- 13.08
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 DK070855, T32 AI005284, K99 DK120897, K99 GM129415)
- Howard Hughes Medical Institute
- Welch Foundation (I-1874)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- gut microbiota, circadian rhythm, HDAC3, small intestinal epithelial cells, epigenetic regulation, metabolic gene expression, lipid metabolism, nutrient transport, estrogen-related receptor alpha, fat absorption, obesity, high-fat diet, jet lag, sleep disruption
- MeSH terms
- Gastrointestinal Microbiome, ERRalpha Estrogen-Related Receptor, Histone Deacetylase 3, Acetylation, Animals, Chromatin, Circadian Rhythm, Colon, Epithelial Cells, Germ-Free Life, Histone Deacetylases, Intestine, Small, Mice, Inbred C57BL, Obesity, Receptors, Estrogen, Mice, Knockout, CD36 Antigens, Jet Lag Syndrome, Lipid Metabolism, Mice, Diet, High-Fat
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