Cited by 2,003Gut microbiota and healthAnimal Nutrition and PhysiologyGastrointestinal motility and disorders

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The Microbiome and Butyrate Regulate Energy Metabolism and Autophagy in the Mammalian Colon

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Donohoe, Dallas R., Garge, Nikhil, Zhang, Xinxin, Sun, Wei, O'Connell, Thomas M., Bunger, Maureen K., Bultman, Scott J.·2011·Cell Metabolism

DOI 10.1016/j.cmet.2011.02.018PMC PMC3099420

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Abstract

The microbiome is being characterized by large-scale sequencing efforts, yet it is not known whether it regulates host metabolism in a general versus tissue-specific manner or which bacterial metabolites are important. Here, we demonstrate that microbiota have a strong effect on energy homeostasis in the colon compared to other tissues. This tissue specificity is due to colonocytes utilizing bacterially produced butyrate as their primary energy source. Colonocytes from germfree mice are in an energy-deprived state and exhibit decreased expression of enzymes that catalyze key steps in intermediary metabolism including the TCA cycle. Consequently, there is a marked decrease in NADH/NAD(+), oxidative phosphorylation, and ATP levels, which results in AMPK activation, p27(kip1) phosphorylation, and autophagy. When butyrate is added to germfree colonocytes, it rescues their deficit in mitochondrial respiration and prevents them from undergoing autophagy. The mechanism is due to butyrate acting as an energy source rather than as an HDAC inhibitor.

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Authors: Donohoe, D. R., Garge, N., Zhang, X., Sun, W., O'Connell, T. M., Bunger, M. K., & Bultman, S. J.
Affiliations: University of North Carolina at Chapel Hill (US)
RTI International (US)
Corresponding author: Bultman, Scott J.
ORCID: Donohoe, Dallas R.
Zhang, Xinxin
Sun, Wei
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2011-05
Volume: 13
Issue: 5
Pages: 517-526
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2011.02.018
PMC: PMC3099420
OpenAlex: W2082578477
Cited by: 2,003
References: 47
Citations by year: 2026: 203 · 2025: 192 · 2024: 170 · 2023: 171 · 2022: 190 · 2021: 228 · 2020: 182 · 2019: 148 · 2018: 115 · 2017: 104 · 2016: 96 · 2015: 68 · 2014: 56 · 2013: 44 · 2012: 23
FWCI: 17.16
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 844 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
UNC Libraries
Funders: National Institutes of Health (CA125237)
Prevent Cancer Foundation
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords: gut microbiota, butyrate, colonic epithelial cells, energy metabolism, autophagy, germ-free mice, TCA cycle, oxidative phosphorylation, AMPK, p27, mitochondrial respiration, bacterial metabolites, energy homeostasis
MeSH terms: Animals, Autophagy, Butyrates, Cells, Cultured, Colon, Energy Metabolism, Germ-Free Life, Glucose, Male, Mice, Inbred C57BL, Mitochondria, NAD, Magnetic Resonance Spectroscopy, Oxidative Phosphorylation, Phosphorylation, Blotting, Western, Signal Transduction, Biomarkers, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Cyclin-Dependent Kinase Inhibitor p27, Mice, Metagenome, AMP-Activated Protein Kinases, Metabolomics

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The Microbiome and Butyrate Regulate Energy Metabolism and Autophagy in the Mammalian Colon

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