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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Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments
Smyth, G. K. (2004) · Statistical Applications in Genetics and Molecular Biology · doi:10.2202/1544-6115.1027 · Cited by 11,829
A human gut microbial gene catalogue established by metagenomic sequencing
MetaHIT Consortium, Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., et al. (2010) · Nature · doi:10.1038/nature08821 · Cited by 11,624
Self-citation
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Eckburg, P. B., Bik, E. M., Bernstein, C. N., Purdom, E., Dethlefsen, L., Sargent, M., Gill, S. R., Nelson, K. E., & Relman, D. A. (2005) · Science · doi:10.1126/science.1110591 · Cited by 7,913 · cited 2×
“INTRODUCTION Diverse microbial communities reside at various sites within the human body (Camp et al., 2009; Eckburg et al., 2005; Savage, 1977).”
A core gut microbiome in obese and lean twins
Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., Sogin, M. L., Jones, W. J., Roe, B. A., Affourtit, J. P., et al. (2009) · Nature · doi:10.1038/nature07540 · Cited by 7,823 · cited 3×
“These microbiota and their genomes, referred to collectively as the microbiome, are being characterized by metagenomic sequencing as part of the Human Microbiome Project (Gill et al., 2006; Hildebrandt et al., 2009; Kurokawa et al., 2007; Qin et al.; Turnbaugh et al., 2009; Turnbaugh et al., 2007).”
The gut microbiota as an environmental factor that regulates fat storage
Bäckhed, F., Ding, H., Wang, T., Hooper, L. V., Koh, G. Y., Nagy, A., Semenkovich, C. F., & Gordon, J. I. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407076101 · Cited by 6,245 · cited 8×
“These studies support the idea that microbes increase host metabolic efficiency (Backhed et al., 2004; Turnbaugh et al., 2008; Turnbaugh and Gordon, 2009; Turnbaugh et al., 2009; Turnbaugh et al., 2006).”
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Metagenomic Analysis of the Human Distal Gut Microbiome
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Regulation mechanisms and signaling pathways of autophagy
He, C., & Klionsky, D. J. (2009) · Annual Review of Genetics · doi:10.1146/annurev-genet-102808-114910 · Cited by 3,609 · cited 1×
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“These studies support the idea that microbes increase host metabolic efficiency (Backhed et al., 2004; Turnbaugh et al., 2008; Turnbaugh and Gordon, 2009; Turnbaugh et al., 2009; Turnbaugh et al., 2006).”

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Sohail, M. U., Thani, A. A. A., Anwar, H., Rizzi, R., & Marei, H. E. S. (2017) · Journal of Diabetes Research · doi:10.1155/2017/9631435 · Cited by 104
“Both hepatocytes and enterocytes are reported as energy deprived and have an overexpression of AMPactivated protein kinase (AMPK), which determines cellular energy status in gnotobiotic germ-free mice [21, 22].”
Background
Microbial community design: methods, applications, and opportunities
Eng, A., & Borenstein, E. (2019) · Current Opinion in Biotechnology · doi:10.1016/j.copbio.2019.03.002 · Cited by 105
“com microbially produced butyrate contributes to colonic health via its function as an important energy source [1] and anti-inflammatory agent [2].”
Background
In vitro Characterization of Gut Microbiota-Derived Bacterial Strains With Neuroprotective Properties
Ahmed, S., Busetti, A., Fotiadou, P., Jose, N. V., Reid, S., Georgieva, M., Brown, S., Dunbar, H., Beurket-Ascencio, G., Delday, M. I., et al. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00402 · Cited by 100
“Butyric acid has the potential to beneficially impact Parkinson’s symptoms by reducing inflammation, increasing dopamine synthesis (by improving the amount of free niacin that is available for dopamine synthesis) and boosting mitochondrial function to provide cells with more energy (Donohoe et al., 2011; Bourassa et a…”
Background
LSD1 mediates microbial metabolite butyrate-induced thermogenesis in brown and white adipose tissue
Wang, D., Liu, C.-D., Li, H., Tian, M.-L., Pan, J., Shu, G., Jiang, Q., Yin, Y., & Zhang, L. (2019) · Metabolism · doi:10.1016/j.metabol.2019.154011 · Cited by 103
An orally administered butyrate-releasing xylan derivative reduces inflammation in dextran sulphate sodium-induced murine colitis
Zha, Z., Lv, Y., Tang, H., Li, T., Miao, Y., Cheng, J., Wang, G., Tan, Y., Zhu, Y., Xing, X., et al. (2019) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2019.11.159 · Cited by 101
Intestinal microbiota: a new force in cancer immunotherapy
Dai, Z., Zhang, J., Wu, Q., Fang, H., Shi, C., Li, Z., Lin, C., Tang, D., & Wang, D. (2020) · Cell Communication and Signaling · doi:10.1186/s12964-020-00599-6 · Cited by 98
“Microbial-derived butyrate inhibits the activity of histone deacetylase, which activates Foxp3 via a G-protein coupled receptor (GPCR) and promotes differentiation of naive T cells into Tregs, eliminating anti-tumor immune responses [70, 71].”
Background
Obesity and the gut microbiome: Striving for causality
Harley, I. T. W., & Karp, C. L. (2012) · Molecular Metabolism · doi:10.1016/j.molmet.2012.07.002 · Cited by 99
“26 microbiomes with differential capacity for energy harvest have been described [29], further study will be necessary to define the contribution of microbial energy harvest capacity to weight regulation.”
Background
Gut microbiota and mTOR signaling: Insight on a new pathophysiological interaction
Noureldein, M. H., & Eid, A. A. (2018) · Microbial Pathogenesis · doi:10.1016/j.micpath.2018.03.021 · Cited by 99
Mechanism of deoxynivalenol mediated gastrointestinal toxicity: Insights from mitochondrial dysfunction
Wang, S., Wu, K., Xue, D., Zhang, C., Rajput, S. A., & Qi, D. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112214 · Cited by 100
The Intercellular Metabolic Interplay between Tumor and Immune Cells
Wang, T., Liu, G., & Wang, R. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00358 · Cited by 96
“indoleamine-2,3-dioxygenase for cancer therapy: can we see the wood for the trees? Nat Rev Cancer (2009) 9(6):445–52.”
Background
ANGPTL4 expression induced by butyrate and rosiglitazone in human intestinal epithelial cells utilizes independent pathways
Korecka, A., de Wouters, T., Cultrone, A., Lapaque, N., Pettersson, S., Dore, J. M., Blottière, H. M., & Arulampalam, V. (2013) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00293.2012 · Cited by 96
“23 and 47) and are the main energy source for colonocytes (18, 19, 45).”
Background
Role of the microbiome in occurrence, development and treatment of pancreatic cancer
Wang, Y., Yang, G., You, L., Yang, J., Feng, M., Qiu, J., Zhao, F., Liu, Y., Cao, Z., Zheng, L., et al. (2019) · Molecular Cancer · doi:10.1186/s12943-019-1103-2 · Cited by 97
Vegetarian Diet in Chronic Kidney Disease—A Friend or Foe
Gluba-Brzózka, A., Franczyk, B., & Rysz, J. (2017) · Nutrients · doi:10.3390/nu9040374 · Cited by 98
Gut microbiome interventions in human health and diseases
Nie, P., Li, Z., Wang, Y., Zhang, Y., Zhao, M., Luo, J., Du, S., Deng, Z., Chen, J., Wang, Y., et al. (2019) · Medicinal Research Reviews · doi:10.1002/med.21584 · Cited by 94
A single strain of Bacteroides fragilis protects gut integrity and reduces GVHD
Sofi, M. H., Wu, Y., Ticer, T. D., Schutt, S. D., Bastian, D. A., Choi, H.-J., Tian, L., Mealer, C., Liu, C., Westwater, C., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.136841 · Cited by 97
Gut microbiome, metabolome, and allergic diseases
Hirata, S., & Kunisawa, J. (2017) · Allergology International · doi:10.1016/j.alit.2017.06.008 · Cited by 95
The role of prebiotics in cognition, anxiety, and depression
de Paiva, I. H. R., Duarte-Silva, E. P., & Peixoto, C. A. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.03.006 · Cited by 100
The Metabolic Role and Therapeutic Potential of the Microbiome
Olofsson, L. E., & Bäckhed, F. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnac004 · Cited by 99
Neoagarotetraose protects mice against intense exercise‐induced fatigue damage by modulating gut microbial composition and function
Zhang, N., Mao, X., Li, R. W., Hou, E., Wang, Y., Xue, C., & Tang, Q. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201600585 · Cited by 93
Evolving Concepts: How Diet and the Intestinal Microbiome Act as Modulators of Breast Malignancy
Shapira, I., Sultan, K. S., Lee, A., & Taioli, E. (2013) · ISRN Oncology · doi:10.1155/2013/693920 · Cited by 96
“By-products of bacterial fermentation of soluble fibers are short chain fatty acids (acetate, propionate, and butyrate), the preferred source of energy for colonocytes [56].”
Background
The Gut Microbiota in Women Suffering from Gestational Diabetes Mellitus with the Failure of Glycemic Control by Lifestyle Modification
Ye, G., Zhang, L., Wang, M., Chen, Y., Gu, S., Wang, K., Leng, J., Gu, Y., & Xie, X. (2019) · Journal of Diabetes Research · doi:10.1155/2019/6081248 · Cited by 95
“If butyric acid is added to the colon in time, then it can rescue the defects of mitochondrial respiration and prevent autophagy in colonocytes [60].”
Implication of G Protein-Coupled Receptor 43 in Intestinal Inflammation: A Mini-Review
Yang, G., Chen, S., Deng, B., Tan, C., Deng, J., Zhu, G., Yin, Y., & Ren, W. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01434 · Cited by 95
Interactions between Host PPARs and Gut Microbiota in Health and Disease
Hasan, A. U., Rahman, A., & Kobori, H. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020387 · Cited by 93
“Among them, butyrate is the main carbon source for the intestinal epithelial cells [35].”
Background
Gut–Liver Immune Response and Gut Microbiota Profiling Reveal the Pathogenic Mechanisms of Vibrio harveyi in Pearl Gentian Grouper (Epinephelus lanceolatus♂ × E. fuscoguttatus♀)
Deng, Y., Zhang, Y., Chen, H., Xu, L., Wang, Q., & Feng, J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.607754 · Cited by 97
Role of microbiota short-chain fatty acids in the pathogenesis of autoimmune diseases
Rasouli‐Saravani, A., Jahankhani, K., Moradi, S., Gorgani, M., Shafaghat, Z., Mirsanei, Z., Mehmandar‐Oskuie, A., & Mirzaei, R. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114620 · Cited by 98
Know your neighbor: Microbiota and host epithelial cells interact locally to control intestinal function and physiology
Sommer, F., & Bäckhed, F. (2016) · BioEssays · doi:10.1002/bies.201500151 · Cited by 96
Antibiotic-driven dysbiosis in early life disrupts indole-3-propionic acid production and exacerbates allergic airway inflammation in adulthood
Perdijk, O., Butler, A., Macowan, M. G., Chatzis, R., Bulanda, E., Grant, R. D., Harris, N. L., Wypych, T. P., & Marsland, B. J. (2024) · Immunity · doi:10.1016/j.immuni.2024.06.010 · Cited by 92
Interactions between the microbiota and enteric nervous system during gut-brain disorders
Fried, S. G., Wemelle, E., Cani, P. D., & Knauf, C. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2021.108721 · Cited by 95
Metagenomic cross-talk: the regulatory interplay between immunogenomics and the microbiome
Levy, M., Thaiss, C. A., & Elinav, E. (2015) · Genome Medicine · doi:10.1186/s13073-015-0249-9 · Cited by 94
“Despite the enormous influence of intestinal microbial colonization on gene regulation processes in the intestine and in other systems [27–29] the mechanisms mediating this transcriptional reprogramming remain largely elusive.”
Background
Xylooligosaccharide Modulates Gut Microbiota and Alleviates Colonic Inflammation Caused by High Fat Diet Induced Obesity
Fei, Y., Wang, Y., Pang, Y., Wang, W., Zhu, D., Xie, M., Lan, S., & Wang, Z. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2019.01601 · Cited by 91
“SCFAs increase the expression of PGC-1α and AMPK phosphorylation to promote lipid oxidation in tissues (Donohoe et al., 2011).”
Background
The Multiple Roles of Glucose-6-Phosphate Dehydrogenase in Tumorigenesis and Cancer Chemoresistance
Song, J., Sun, H., Zhang, S., & Shan, C. (2022) · Life · doi:10.3390/life12020271 · Cited by 88
From metagenomic data to personalized in silico microbiotas: predicting dietary supplements for Crohn’s disease
Bauer, E., & Thiele, I. (2018) · npj Systems Biology and Applications · doi:10.1038/s41540-018-0063-2 · Cited by 88
Site-specific acylation of a bacterial virulence regulator attenuates infection
Zhang, Z. J., Pedicord, V. A., Peng, T., & Hang, H. C. (2019) · Nature Chemical Biology · doi:10.1038/s41589-019-0392-5 · Cited by 86
Dietary sodium propionate affects mucosal immune parameters, growth and appetite related genes expression: Insights from zebrafish model
Hoseinifar, S. H., Safari, R., & Dadar, M. (2016) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2016.11.008 · Cited by 88
Microbiome manipulation modifies sex-specific risk for autoimmunity
Markle, J., Frank, D. N., Adeli, K., von Bergen�, M., & Danska, J. S. (2014) · Gut Microbes · doi:10.4161/gmic.29795 · Cited by 88
Controversial Roles of Gut Microbiota-Derived Short-Chain Fatty Acids (SCFAs) on Pancreatic β-Cell Growth and Insulin Secretion
Liu, J., Segovia, I., Yuan, X., & Gao, Z. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21030910 · Cited by 91
Dietary genistein increases microbiota-derived short chain fatty acid levels, modulates homeostasis of the aging gut, and extends healthspan and lifespan
Hou, Q., Huang, J., Zhao, L., Pan, X., Liao, C., Jiang, Q., Lei, J., Guo, F., Cui, J., Guo, Y., et al. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106676 · Cited by 88
Sodium butyrate protects against oxidative stress in HepG2 cells through modulating Nrf2 pathway and mitochondrial function
Xing, X., Jiang, Z., Xue Ming, T. A. N. G., Wang, P., Li, Y., Sun, Y., Le, G., & Zou, S. (2016) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-017-0568-y · Cited by 85
“NaBu has also been shown to regulate the glycolytic pathway and oxidative phosphorylation in breast cancer cells and mammalian colonocytes, acting as an HDAC inhibitor or an energy source [6, 24].”
Background
The Anti-colitis Effect of Schisandra chinensis Polysaccharide Is Associated With the Regulation of the Composition and Metabolism of Gut Microbiota
Su, L., Mao, C., Wang, X., Li, L., Tong, H., Mao, J., Ji, D., Lu, T., Hao, M., Huang, Z., et al. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.519479 · Cited by 87
“It has been proved that Clostridium coccoides can protect the colon from inflammatory damage (Donohoe et al., 2011; Brown et al., 2012).”
Background
Mucin-2 knockout is a model of intercellular junction defects, mitochondrial damage and ATP depletion in the intestinal epithelium
Borisova, M. A., Achasova, K. M., Morozova, K. N., Andreyeva, E. N., Litvinova, E. A., Ogienko, A. A., Morozova, M. V., Berkaeva, M. B., Владимировна, К. Е., & Kozhevnikova, E. N. (2020) · Scientific Reports · doi:10.1038/s41598-020-78141-4 · Cited by 86
Gut and vaginal microbiomes on steroids: implications for women’s health
Graham, M. E., Herbert, W. G., Song, S., Raman, H. N., Zhu, J. E., Gonzalez, P. E., Walther-Antonio, M. R. S., & Tetel, M. J. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.04.014 · Cited by 87
“SCFAs, a product of fiber fermentation by GM, are associated with gut health and have immunomodulating effects [34].”
Background
Mitochondrial function in intestinal epithelium homeostasis and modulation in diet-induced obesity
Guerbette, T., Boudry, G., & Lan, A. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101546 · Cited by 100
Targeting gut barrier dysfunction with phytotherapies: Effective strategy against chronic diseases
Dey, P. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105135 · Cited by 86

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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