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The Microbiome and Butyrate Regulate Energy Metabolism and Autophagy in the Mammalian Colon
Open accessAbstract
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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“The pathophysiological consequences of this condition are predictable (epithelial cell death and dysregulated inflammation), but the clinical consequences are unknown.”
From The microbiome and critical illness (2016) · cites this paper as [75]
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An obesity-associated gut microbiome with increased capacity for energy harvest
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006) · Nature · doi:10.1038/nature05414 · Cited by 12,444
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-citationDiversity of the Human Intestinal Microbial Flora
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).”
InfluentialTurnbaugh, P. J., Ley, R. E., Hamady, M., Fraser-Liggett, C. M., Knight, R., & Gordon, J. I. (2007) · Nature · doi:10.1038/nature06244 · Cited by 6,091 · cited 1×
“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).”
Metagenomic Analysis of the Human Distal Gut Microbiome
Gill, S. R., Pop, M., DeBoy, R. T., Eckburg, P. B., Turnbaugh, P. J., Samuel, B. S., Gordon, J. I., Relman, D. A., Fraser-Liggett, C. M., & Nelson, K. E. (2006) · Science · doi:10.1126/science.1124234 · Cited by 4,699 · cited 2×
“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).”
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×
“In response to nutrient deprivation, AMPK activation induces autophagy, which is a catabolic process where the cell degrades its own cellular components in an attempt to maintain energy homeostasis (He and Klionsky, 2009; Yang and Klionsky, 2009).”
Turnbaugh, P. J., Bäckhed, F., Fulton, L., & Gordon, J. I. (2008) · Cell Host & Microbe · doi:10.1016/j.chom.2008.02.015 · Cited by 2,915 · cited 1×
“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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den Besten, G., van Eunen, K., Groen, A. K., Venema, K., Reijngoud, D.-J., & Bakker, B. M. (2013) · Journal of Lipid Research · doi:10.1194/jlr.r036012 · Cited by 5,048
“Donohoe et al. ( 18 ) showed that colonocytes of germ-free mice exhibit a defi cit in mitochondrial respiration and undergo autophagy.”
Functional interactions between the gut microbiota and host metabolism
Tremaroli, V., & Bäckhed, F. (2012) · Nature · doi:10.1038/nature11552 · Cited by 4,387
Parada Venegas, D., De la Fuente, M. K., Landskron, G., González, M. J., Quera, R., Dijkstra, G., Harmsen, H. J. M., Faber, K. N., & Hermoso, M. A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00277 · Cited by 3,820
“Recolonization of GF mice with butyrate-producing bacteria and butyrate treatment of GF colonocytes ex-vivo, increases oxidative phosphorylation and suppresses autophagy to normal levels (17), implying the importance of host-microbe interaction in energy metabolism of colonic epithelium.”
BackgroundThe role of short chain fatty acids in health and disease
Tan, J., McKenzie, C., Potamitis, M., Thorburn, A. N., Mackay, C. R., & Macia, L. (2014) · Advances in immunology · doi:10.1016/b978-0-12-800100-4.00003-9 · Cited by 2,425
Diet–microbiota interactions as moderators of human metabolism
Sonnenburg, J. L., & Bäckhed, F. (2016) · Nature · doi:10.1038/nature18846 · Cited by 2,257
Microbiota-Generated Metabolites Promote Metabolic Benefits via Gut-Brain Neural Circuits
De Vadder, F., Kovatcheva-Datchary, P., Goncalves, D., Vinera, J., Zitoun, C., Duchampt, A., Bäckhed, F., & Mithieux, G. (2014) · Cell · doi:10.1016/j.cell.2013.12.016 · Cited by 2,200
“First, butyrate is a key energy substrate for both colonocytes and enterocytes (Donohoe et al., 2011).”
Kelly, C. J., Zheng, L., Campbell, E. L., Saeedi, B., Scholz, C. C., Bayless, A. J., Wilson, K. E., Glover, L. E., Kominsky, D. J., Magnuson, A., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.03.005 · Cited by 1,716
“Donohoe et al. (2011) showed that compared with conventionalized mice, the colonocytes of germ-free mice are ATP deficient and the provision of butyrate can reverse this energy deficit by restoring oxidative respiration.”
Schwabe, R. F., & Jobin, C. (2013) · Nature Reviews Cancer · doi:10.1038/nrc3610 · Cited by 1,689
Gut microbiota in cardiovascular health and disease
Tang, W. H. W., Kitai, T., & Hazen, S. L. (2017) · Circulation Research · doi:10.1161/circresaha.117.309715 · Cited by 1,670
“SCFAs, in particular butyrate, serve as energy substrates for epithelial cells of the gut.(95,96)”
BackgroundObesity and cancer risk: Emerging biological mechanisms and perspectives
Avgerinos, K. I., Spyrou, N., Mantzoros, C. S., & Dalamaga, M. (2019) · Metabolism · doi:10.1016/j.metabol.2018.11.001 · Cited by 1,567
“Butyrate, an abundant bacterial metabolite, inhibits deacetylation of histones whereas certain species of bacteria can alter the non-coding RNA profile of host cells [210-212].”
BackgroundThe impact of diet and lifestyle on gut microbiota and human health
Conlon, M., & Bird, A. (2014) · Nutrients · doi:10.3390/nu7010017 · Cited by 1,567
“abundant and physiologically important products, namely short chain fatty acids (SCFA) which act as key sources of energy for colorectal tissues and bacteria, and promote cellular mechanisms that maintain tissue integrity [12–14].”
BackgroundSCFA: mechanisms and functional importance in the gut
Martin‐Gallausiaux, C., Marinelli, L., Blottière, H. M., Larraufie, P., & Lapaque, N. (2020) · Proceedings of The Nutrition Society · doi:10.1017/s0029665120006916 · Cited by 1,585
An insight into gut microbiota and its functionalities
Adak, A., & Khan, M. R. (2019) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2943-4 · Cited by 1,485
Gut microbial metabolites as multi-kingdom intermediates
Krautkramer, K. A., Fan, J., & Bäckhed, F. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-0438-4 · Cited by 1,398
Pelaseyed, T., Bergström, J. H., Gustafsson, J. K., Ermund, A., Birchenough, G. M. H., Schütte, A., van der Post, S., Svensson, F., Rodríguez‐Piñeiro, A. M., Nyström, E. E. L., et al. (2014) · Immunological Reviews · doi:10.1111/imr.12182 · Cited by 1,363
“Substantial quantities of short fatty acids are absorbed by the tissue epithelial cells; for example, butyrate seems to have a key role to play in colon epithelial protection and metabolism (49, 50).”
Bile acids and the gut microbiome
Ridlon, J. M., Kang, D. J., Hylemon, P. B., & Bajaj, J. S. (2014) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000057 · Cited by 1,329
“From these substrates, gut bacteria produce short-chain fatty acids (acetate, propionate, butyrate) that can account for up to 10% of the total caloric intake per day [2].”
BackgroundRegulation of immune cell function by short‐chain fatty acids
Corrêa‐Oliveira, R., Fachi, J. L., Vieira, A., Sato, F. T., & Vinolo, M. A. R. (2016) · Clinical & Translational Immunology · doi:10.1038/cti.2016.17 · Cited by 1,346
Oliphant, K., & Allen-Vercoe, E. (2019) · Microbiome · doi:10.1186/s40168-019-0704-8 · Cited by 1,327
Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota
Fusco, W. G., Bernabeu, M., Cintoni, M., Porcari, S., Rinninella, E., Kaitsas, F., Lener, E., Mele, M. C., Gasbarrini, A., Collado, M. C., et al. (2023) · Nutrients · doi:10.3390/nu15092211 · Cited by 1,397
“First, SCFAs-producing taxa are usually commensal, beneficial bacteria, with a direct positive effect on the gut barrier and immunity beyond the production of SCFAs [55,114].”
BackgroundHabitat degradation impacts black howler monkey ( Alouatta pigra ) gastrointestinal microbiomes
Amato, K. R., Yeoman, C. J., Kent, A. D., Righini, N., Carbonero, F. G., Estrada, A., Gaskins, H. R., Stumpf, R. M., Yıldırım, S., Torralba, M., et al. (2013) · The ISME Journal · doi:10.1038/ismej.2013.16 · Cited by 1,224
“Butyrogenic and acetogenic metabolism are particularly beneficial as they allow optimal energy gain, and butyrate promotes intestinal development and health (Donohoe et al., 2011; Grootaert et al., 2011).”
BackgroundMicrobiota-activated PPAR-γ signaling inhibits dysbiotic Enterobacteriaceae expansion
Byndloss, M. X., Olsan, E. E., Rivera-Chávez, F., Tiffany, C. R., Cevallos, S. A., Lokken, K. L., Torres, T. P., Byndloss, A. J., Faber, F., Gao, Y., et al. (2017) · Science · doi:10.1126/science.aam9949 · Cited by 1,260
“We exposed the model epithelia to butyrate, a fermentation product of the gut microbiota that serves as the main carbon source of colonic epithelial cells (colonocytes) (5).”
Lin, H. V., Frassetto, A., Kowalik Jr, E. J., Nawrocki, A. R., Lu, M. M., Kosinski, J. R., Hubert, J. A., Szeto, D., Yao, X., Forrest, G., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035240 · Cited by 1,378
“Butyrate was also shown to regulate autophagy in colonocytes by acting as an energy source [28].”
BackgroundThe oral microbiome – an update for oral healthcare professionals
Kilian, M., Chapple, I. L. C., Hannig, M., Marsh, P. D., Meuric, V., Pedersen, A. M. L., Tonetti, M. S., Wade, W. G., & Zaura, E. (2016) · British Dental Journal · doi:10.1038/sj.bdj.2016.865 · Cited by 1,269
Human breast milk: A review on its composition and bioactivity
Andreas, N. J., Kampmann, B., & Doaré, K. L. (2015) · Early Human Development · doi:10.1016/j.earlhumdev.2015.08.013 · Cited by 1,132
“Short-chain fatty acids (SCFA) found in breast milk are also an important source of energy [22], as well as being essential for normal maturation of the gastrointestinal tract [23].”
BackgroundThe Human Gut Microbiome – A Potential Controller of Wellness and Disease
Kho, Z. Y., & Lal, S. K. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.01835 · Cited by 1,180
“Butyrate-producing microbes rescued the deficit mitochondrial respiration, ATP synthesis and autophagy in colonocytes of germfree mice (Donohoe et al., 2011), proving the importance of butyrate in colonic cellular respiration and energy production.”
BackgroundChemical transformation of xenobiotics by the human gut microbiota
Koppel, N., Maini Rekdal, V., & Balskus, E. P. (2017) · Science · doi:10.1126/science.aag2770 · Cited by 1,080
Free Fatty Acid Receptors in Health and Disease
Kimura, I., Ichimura, A., Ohue‐Kitano, R., & Igarashi, M. (2019) · Physiological Reviews · doi:10.1152/physrev.00041.2018 · Cited by 1,063
“Simultaneously, FFAs can be transported from the plasma to BAT, brown adipose tissue; CCK, cholecystokinin; FFAR, free fatty acid receptor; FGF21, fibroblast growth factor-21; GIP, gastric inhibitory polypeptide; GLP-1, glucagon-like peptide 1; NLRP, NACHT, LRR, and PYD domain-containing protein; PYY, peptide YY; TNF-…”
BackgroundInfluentialNew insights into activation and function of the AMPK
Steinberg, G. R., & Hardie, D. G. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00547-x · Cited by 1,074
Commensal bacteria at the interface of host metabolism and the immune system
Brestoff, J. R., & Artis, D. (2013) · Nature Immunology · doi:10.1038/ni.2640 · Cited by 945
From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways
Rogers, G. B., Keating, D. J., Young, R. L., Wong, M.-L., Licinio, J., & Wesselingh, S. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.50 · Cited by 969
Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation
Kasubuchi, M., Hasegawa, S., Hiramatsu, T., Ichimura, A., & Kimura, I. (2015) · Nutrients · doi:10.3390/nu7042839 · Cited by 904
“in muscle and liver tissues, and the expression of PGC-1α and mitochondrial uncoupling protein-1 (UCP-1) in brown adipose tissues [21].”
BackgroundHill‐Burns, E. M., Debelius, J. W., Morton, J. T., Wissemann, W. T., Lewis, M. R., Wallen, Z. D., Peddada, S. D., Factor, S. A., Molho, E., Zabetian, C. P., et al. (2017) · Movement Disorders · doi:10.1002/mds.26942 · Cited by 874
Obesity, inflammation, and the gut microbiota
Cox, A. J., West, N. P., & Cripps, A. W. (2015) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(14)70134-2 · Cited by 869
New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD
Larabi, A. B., Barnich, N., & Nguyen, H. T. T. (2019) · Autophagy · doi:10.1080/15548627.2019.1635384 · Cited by 860
“pared to conventionally raised control mice [36].”
BackgroundInfluentialGut microbiota–generated metabolites in animal health and disease
Lee, W.-J., & Hase, K. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1535 · Cited by 756
Exercise alters gut microbiota composition and function in lean and obese humans
ALLEN, J. M., MAILING, L. J., NIEMIRO, G. M., MOORE, R., COOK, M. D., WHITE, B. A., HOLSCHER, H. D., & WOODS, J. A. (2018) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000001495 · Cited by 820
“Butyrate is a primary fuel source for colonocytes (39), is required for maintaining gut barrier function (40), and is a critical metabolite regulating the antiinflammatory/regulatory phenotypes of gut-resident immune cells (41).”
BackgroundThe Reciprocal Interactions between Polyphenols and Gut Microbiota and Effects on Bioaccessibility
Özdal, T., Sela, D. A., Xiao, J., Boyacıoğlu, D., Chen, F., & Çapanoğlu, E. (2016) · Nutrients · doi:10.3390/nu8020078 · Cited by 842
“Higher bioavailability of phenolic compounds, and the resultant beneficial health effects as determined by the consumption of whole grains, vegetables and fruits, can be related to the end-products of microbial metabolism forming short-chain fatty acids such as butyrate, and phenolic acids such as protocatechuic acid…”
BackgroundRomano, K. A., Vivas, E. I., Amador-Noguez, D., & Rey, F. E. (2015) · mBio · doi:10.1128/mbio.02481-14 · Cited by 777
Colonocyte metabolism shapes the gut microbiota
Litvak, Y., Byndloss, M. X., & Bäumler, A. J. (2018) · Science · doi:10.1126/science.aat9076 · Cited by 789
Long-term benefit of microbiota transfer therapy on autism symptoms and gut microbiota
Kang, D.-W., Adams, J. B., Coleman, D. M., Pollard, E. L., Maldonado, J., McDonough-Means, S., Caporaso, J. G., & Krajmalnik-Brown, R. (2019) · Scientific Reports · doi:10.1038/s41598-019-42183-0 · Cited by 749
The Colonic Crypt Protects Stem Cells from Microbiota-Derived Metabolites
Kaiko, G. E., Ryu, H., Koues, O. I., Collins, P. L., Solnica‐Krezel, L., Pearce, E. J., Pearce, E. L., Oltz, E. M., & Stappenbeck, T. S. (2016) · Cell · doi:10.1016/j.cell.2016.05.018 · Cited by 761
“metabolic stress and upregulates the autophagy pathway for survival (Donohoe et al., 2011).”
Short chain fatty acids: Microbial metabolites for gut-brain axis signalling
O’Riordan, K. J., Collins, M., Moloney, G. M., Knox, E. G., Aburto, M. R., Fülling, C., Morley, S. J., Clarke, G. A., Schellekens, H., & Cryan, J. F. (2022) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2022.111572 · Cited by 788
Bachem, A., Makhlouf, C., Binger, K. J., de Souza, D. P., Tull, D., Hochheiser, K., Whitney, P. G., Fernandez-Ruiz, D., Dähling, S., Kastenmüller, W., et al. (2019) · Immunity · doi:10.1016/j.immuni.2019.06.002 · Cited by 702
Li, F., Jiang, C., Krausz, K. W., Li, Y., Albert, I., Hao, H., Fabre, K. M., Mitchell, J. B., Patterson, A. D., & Gonzalez, F. J. (2013) · Nature Communications · doi:10.1038/ncomms3384 · Cited by 705
Trompette, A., Gollwitzer, E. S., Pattaroni, C., Lopez-Mejia, I. C., Riva, E., Pernot, J., Ubags, N., Fajas, L., Nicod, L. P., & Marsland, B. J. (2018) · Immunity · doi:10.1016/j.immuni.2018.04.022 · Cited by 678
“…of SCFAs in immune cell metabolism (Kim et al., 2014); following conversion into acetyl-CoA and integration into the Krebs cycle (Blad et al., 2012; Donohoe et al., 2011; Kim et al., 2014), they can influence T helper cell differentiation via mTOR signaling (Kim et al., 2014) or accelerate recall…”
BackgroundInfluentialDiet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease
Brown, K., DeCoffe, D., Molcan, E., & Gibson, D. L. (2012) · Nutrients · doi:10.3390/nu4081095 · Cited by 700
“Clostridium coccoides are major producers of short chain fatty acids, particularly butyrate, which is an energy source for colonocytes and has been shown to protect against damaging inflammatory responses [42].”
BackgroundGut microbiome and aging: physiological and mechanistic insights
Nagpal, R., Mainali, R., Ahmadi, S., Wang, S., Singh, R., Kavanagh, K., Kitzman, D. W., Kushugulova, A., Marotta, F., & Yadav, H. (2018) · Nutrition and Healthy Aging · doi:10.3233/nha-170030 · Cited by 670
“[148] Donohoe DR, Garge N, Zhang X, Sun W, O’Connell TM, Bunger MK, Bultman SJ.”
BackgroundHoneybee gut microbiota promotes host weight gain via bacterial metabolism and hormonal signaling
Zheng, H., Powell, J. E., Steele, M. I., Dietrich, C., & Moran, N. A. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1701819114 · Cited by 664
“Short-chain fatty acids (SCFAs), namely acetate, propionate, and butyrate, produced by the gut microbiota as main fermentation products of dietary fiber accumulate in the human colon in concentrations up to 80–130 mM (12) and serve as a major energy source for intestinal epithelial cells (13) or as the main respirator…”
BackgroundInsights into the role of the microbiome in obesity and type 2 diabetes
Hartstra, A. V., Bouter, K. E. C., Bäckhed, F., & Nieuwdorp, M. (2015) · Diabetes Care · doi:10.2337/dc14-0769 · Cited by 641
Wong, J., Piceno, Y. M., DeSantis, T. Z., Pahl, M. V., Andersen, G. L., & Vaziri, N. D. (2014) · American Journal of Nephrology · doi:10.1159/000360010 · Cited by 658
“The dependence of colonocytes on butyrate produced by bacteria was demonstrated in an elegant study by Donohoe et al. [37] who showed ATP depletion and autophagy in colonocytes of the germ-free mice and their reversal by addition of butyrate.”
BackgroundButyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health?
Bourassa, M. W., Alim, I., Bultman, S. J., & Ratan, R. R. (2016) · Neuroscience Letters · doi:10.1016/j.neulet.2016.02.009 · Cited by 667
“It was recently shown that germ free mice, which lack a microbiome, had a significantly reduced NADH/NAD+ ratio and reduced ATP levels in the colon compared to conventionally raised mice with a normal microbiome [56].”
Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids
den Besten, G., Lange, K., Havinga, R., van Dijk, T. H., Gerding, A., van Eunen, K., Müller, M. M., Groen, A. K., Hooiveld, G. J. E. J., Bakker, B. M., et al. (2013) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00265.2013 · Cited by 625
“In the 41 last decades it became apparent that SCFAs might play a key role in the prevention and treatment of 42 metabolic syndrome, bowel disorders and certain types of cancer (14, 17, 45, 47).”
BackgroundThe gut microbiota influences skeletal muscle mass and function in mice
Lahiri, S., Kim, H., Garcia-Perez, I., Reza, M. M., Martin, K. A., Kundu, P., Cox, L. M., Selkrig, J., Posma, J. M., Zhang, H., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aan5662 · Cited by 580
Fellows, R., Denizot, J., Stellato, C., Cuomo, A., Jain, P., Stoyanova, E., Balázsi, S., Hajnády, Z., Liebert, A., Kazakevych, J., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02651-5 · Cited by 568
Zhou, L., Zhang, M., Wang, Y., Dorfman, R. G., Liu, H., Yu, T., Chen, X., Tang, D., Xu, L., Yin, Y., et al. (2018) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izy182 · Cited by 525
Dysregulated Microbial Fermentation of Soluble Fiber Induces Cholestatic Liver Cancer
Singh, V., Yeoh, B. S., Chassaing, B., Xiao, X., Saha, P., Aguilera Olvera, R., Lapek, J. D., Zhang, L., Wang, W.-B., Hao, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.09.004 · Cited by 532
Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model
Kasahara, K., Krautkramer, K. A., Org, E., Romano, K. A., Kerby, R. L., Vivas, E. I., Mehrabian, M., Denu, J. M., Bäckhed, F., Lusis, A. J., et al. (2018) · Nature Microbiology · doi:10.1038/s41564-018-0272-x · Cited by 546
Lü, K., Abo, R., Schlieper, K. A., Graffam, M. E., Levine, S. S., Wishnok, J. S., Swenberg, J. A., Tannenbaum, S. R., & Fox, J. G. (2014) · Environmental Health Perspectives · doi:10.1289/ehp.1307429 · Cited by 527
“For example, the gut microbiota has a strong effect on energy homeostasis in the colon, attributed to the use of butyrate produced by gut bacteria as the primary energy source for colonocytes (Donohoe et al. 2011).”
BackgroundSystemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer
Coutzac, C., Jouniaux, J.-M., Paci, A., Schmidt, J., Mallardo, D., Seck, A., Asvatourian, V., Cassard, L., Saulnier, P., Lacroix, L., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-16079-x · Cited by 513
McNabney, S. M., & Henagan, T. M. (2017) · Nutrients · doi:10.3390/nu9121348 · Cited by 529
“For example, isolated colonocytes from germ-free C57BL/6 mice exhibited NADH/NAD+ ratios that were 16-fold lower than their conventionally raised counterparts, as well as 56% lower ATP levels [9].”
BackgroundAlterations of the Gut Microbiome in Hypertension
Yan, Q., Gu, Y., Li, X., Yang, W. Q., Jia, L., Chen, C., Han, X., Huang, Y., Zhao, L., Li, P., et al. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00381 · Cited by 511
“Functionally, SCFAs modulates the gut inflammation and metabolism via functioning as important colonocytes energy source and signaling molecules (Donohoe et al., 2011), suggesting that low level of SCFA production in gut microbiota may be a considerable risk factor of multiple metabolic syndromes…”
BackgroundIntestinal Microbiota in Cardiovascular Health and Disease
Tang, W. H. W., Bäckhed, F., Landmesser, U., & Hazen, S. L. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.03.024 · Cited by 524
“SCFAs, in particular, butyrate, can serve as energy substrates for epithelial cells of the intestines (60,61).”
BackgroundZheng, L., Kelly, C. J., & Colgan, S. P. (2015) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00191.2015 · Cited by 506
Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies
(2022) · doi:10.1186/s13045-022-01273-9 · Cited by 495
“These processes provide intestinal mucosal epithelial cell energy, improve intestinal villus structure, inhibit autophagy, and preserve intestinal homeostasis [89, 90].”
BackgroundCalder, P. C., Bosco, N., Bourdet‐Sicard, R., Capuron, L., Delzenne, N. M., Dore, J. M., Franceschi, C., Lehtinen, M. J., Recker, T., Salvioli, S., et al. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2017.09.001 · Cited by 524
“SCFAs affect the intestinal mucosa (Donohoe et al., 2011) as well as peripheral tissues, influencing host metabolism (Tremaroli and Bäckhed, 2012).”
Microbiome, metabolites and host immunity
Levy, M., Blacher, E., & Elinav, E. (2016) · Current Opinion in Microbiology · doi:10.1016/j.mib.2016.10.003 · Cited by 495
Polyphenol-Mediated Gut Microbiota Modulation: Toward Prebiotics and Further
Rodríguez-Daza, M.-C., Pulido-Mateos, E. C., Lupien‐Meilleur, J., Guyonnet, D., Desjardins, Y., & Roy, D. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.689456 · Cited by 511
“Among the SCFA, butyrate reinforces the intestinal mucosal barrier (41, 42), suppresses proinflammatory effectors in macrophages, and promotes the differentiation of dendritic cells (9).”
BackgroundZeng, H., Umar, S., Rust, B., Lazarova, D., & Bordonaro, M. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20051214 · Cited by 480
“Butyrate is selectively taken up by the colonic epithelium (via monocarboxylate transporter 1 and other transporters) and provides colonocytes with approximately 70% of their energy [70] and is required for energy homeostasis [71,72]; whereas, acetate and propionate are primarily transported to muscle and liver tissue…”
BackgroundGut microbial metabolism drives transformation of MSH2-deficient colon epithelial cells
Belcheva, A., Irrazabal, T., Robertson, S. J., Streutker, C., Maughan, H., Rubino, S., Moriyama, E. H., Copeland, J. K., Surendra, A., Kumar, S., et al. (2014) · Cell · doi:10.1016/j.cell.2014.04.051 · Cited by 473
Donohoe, D. R., Holley, D., Collins, L. B., Montgomery, S. A., Whitmore, A. C., Hillhouse, A., Curry, K. P., Renner, S. W., Greenwalt, A., Ryan, E. P., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0501 · Cited by 489
“Our data also support a molecular mechanism where microbial fermentation of fiber yields butyrate, which serves as the preferred energy source of normal colonocytes and supports homeostasis (11,25) but accumulates in cancerous colonocytes due to the Warburg effect and functions as an HDAC inhibitor to inhibit cell pro…”
BackgroundHealthy infants harbor intestinal bacteria that protect against food allergy
Feehley, T., Plunkett, C. H., Bao, R., Hong, S. M. C., Culleen, E., Belda‐Ferre, P., Campbell, E., Aitoro, R., Nocerino, R., Paparo, L., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0324-z · Cited by 485
Feng, Y., Wang, Y., Wang, P., Huang, Y., & Wang, F. (2018) · Cellular Physiology and Biochemistry · doi:10.1159/000492853 · Cited by 471
Sorbara, M. T., & Pamer, E. G. (2022) · Nature Reviews Microbiology · doi:10.1038/s41579-021-00667-9 · Cited by 468
Microbial dysbiosis-induced obesity: role of gut microbiota in homoeostasis of energy metabolism
Amabebe, E., Robert, F. O., Agbalalah, T., & Orubu, E. S. F. (2020) · British Journal Of Nutrition · doi:10.1017/s0007114520000380 · Cited by 476
The microbiome and critical illness
Dickson, R. P. (2016) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(15)00427-0 · Cited by 460
Trevelline, B. K., Fontaine, S. S., Hartup, B. K., & Kohl, K. D. (2019) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2018.2448 · Cited by 461
Lung microbiome: new insights into the pathogenesis of respiratory diseases
Li, R., Li, J., & Zhou, X. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01722-y · Cited by 483
“417 418 – 420 In addition to SCFAs, polysaccharide A inhibits the production of proin fl ammatory IL-17 and promotes the expression of IL-10 by CD4 + T cells.”
BackgroundHodgkinson, K. M., Abbar, F. E., Dobranowski, P., Manoogian, J., Butcher, J., Figeys, D., Mack, D. R., & Stintzi, A. (2022) · Clinical Nutrition · doi:10.1016/j.clnu.2022.10.024 · Cited by 465
Role of the Microbiome in Energy Regulation and Metabolism
Nieuwdorp, M., Gilijamse, P. W., Pai, N., & Kaplan, L. M. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.02.008 · Cited by 421
Surface components and metabolites of probiotics for regulation of intestinal epithelial barrier
Liu, Q., Yu, Z., Tian, F., Zhao, J., Zhang, H., Zhai, Q., & Chen, W. (2020) · Microbial Cell Factories · doi:10.1186/s12934-020-1289-4 · Cited by 456
Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health
Vernocchi, P., Del Chierico, F., & Putignani, L. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01144 · Cited by 426
Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome
Shoaie, S., Ghaffari, P., Kovatcheva‐Datchary, P., Mardinoğlu, A., Sen, P., Pujos‐Guillot, E., de Wouters, T., Juste, C., Rizkalla, S. W., Chilloux, J., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.07.001 · Cited by 428
“…of dietary polysaccharides in the gut, are an important energy source for colonocytes and also function as signaling molecules, modulating intestinal inflammation and metabolism (Donohoe et al., 2011; Fernandes et al., 2014; Samuel et al., 2008; Smith et al., 2013b; Tolhurst et al., 2012).”
BackgroundInfluentialGut Microbiota: An Integral Moderator in Health and Disease
Feng, Q., Chen, W.-D., & Wang, Y.-D. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00151 · Cited by 407
“For example, Donohoe et al. (2011) reported that microbiota-produced butyrate could provide energy to colonocytes and then prevent autophagy in the colon.”
BackgroundLecomte, V., Kaakoush, N. O., Maloney, C., Raipuria, M., Huinao, K. D., Mitchell, H. M., & Morris, M. J. (2015) · PLoS ONE · doi:10.1371/journal.pone.0126931 · Cited by 432
“A decrease in butyrate content of the gut of germ-free mice has been shown to promote leakiness of the gut barrier [29,77], associated with increased endotoxemia and inflammation.”
BackgroundThe gut-bone axis: How bacterial metabolites bridge the distance
Zaiss, M. M., Jones, R. M., Schett, G., & Pacifici, R. (2019) · Journal of Clinical Investigation · doi:10.1172/jci128521 · Cited by 403
“In addition, efficient intestinal barrier function can be restored upon supplementation of butyrate to the diet (85).”
BackgroundGut microbiota as the key controllers of 'healthy' aging of elderly people
Ragonnaud, E., & Biragyn, A. (2021) · Immunity & Ageing · doi:10.1186/s12979-020-00213-w · Cited by 383
“Extracellular SCFAs are also utilized as substrates for β-oxydation of fatty acids in CD8 T cell [70] and colonocyte metabolism [71] after they are taken up by several G-protein coupled receptors (GPRs).”
BackgroundDietary Fiber Intake and Gut Microbiota in Human Health
Fu, J., Zheng, Y., Gao, Y., & Xu, W. (2022) · Microorganisms · doi:10.3390/microorganisms10122507 · Cited by 462
“SCFAs can be used by gut mucosal cells as energy sources, with butyrate the preferred energy substrate for colonocytes [56,57].”
BackgroundGut microbiota-mediated inflammation in obesity: a link with gastrointestinal cancer
Cani, P. D., & Jordan, B. F. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0025-6 · Cited by 383
Role of microbiota-derived short-chain fatty acids in cancer development and prevention
Mirzaei, R., Afaghi, A., Babakhani, S., Sohrabi, M., Hosseini‐Fard, S. R., Babolhavaeji, K., Akbari, S. K. A., Yousefimashouf, R., & Karampoor, S. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111619 · Cited by 416
Gonçalves, P., Araújo, J. R., & Santo, J. P. D. (2018) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izx029 · Cited by 404
The Role of Short Chain Fatty Acids in Inflammation and Body Health
Du, Y., He, C., An, Y., Huang, Y., Zhang, H., Fu, W., Wang, M., Shan, Z., Xie, J., Yang, Y., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25137379 · Cited by 444
“…receptor-gamma coactivator 1 α (PGC-1 α ) expression and adenosine monophosphate-activated kinase (AMPK) phosphorylation in muscle and liver tissue and PGC-1 α and mitochondrial uncoupling protein-1 (UCP-1) expression in brown adipose tissue, promoting fatty acid oxidation and thermogenesis [92].”
BackgroundRole of microbiota-derived short-chain fatty acids in nervous system disorders
Mirzaei, R., Bouzari, B., Hosseini‐Fard, S. R., Mazaheri, M., Ahmadyousefi, Y., Abdi, M., Jalalifar, S., Karimitabar, Z., Teimoori, A., Keyvani, H., et al. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111661 · Cited by 408
Variable responses of human microbiomes to dietary supplementation with resistant starch
Venkataraman, A., Sieber, J. R., Schmidt, A. W., Waldron, C., Theis, K. R., & Schmidt, T. M. (2016) · Microbiome · doi:10.1186/s40168-016-0178-x · Cited by 392
“The conjugate base of the acid—butyrate—is the preferred energy source for colonocytes [7].”
BackgroundMicrobiota and metabolic diseases
Pascale, A., Marchesi, N., Marelli, C., Coppola, A., Luzi, L., Govoni, S., Giustina, A., & Gazzaruso, C. (2018) · Endocrine · doi:10.1007/s12020-018-1605-5 · Cited by 423
RETRACTED ARTICLE: Role of the gut microbiome in chronic diseases: a narrative review
Vijay, A., & Valdes, A. M. (2022) · European Journal of Clinical Nutrition · doi:10.1038/s41430-021-00991-6 · Cited by 361
RetractedMicrobial Modulation of Energy Availability in the Colon Regulates Intestinal Transit
Wichmann, A., Allahyar, A., Greiner, T. U., Plovier, H., Östergren‐Lundén, G., Larsson, T. P., Drucker, D. J., Delzenne, N. M., Cani, P. D., & Bäckhed, F. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.09.012 · Cited by 380
“Given that colonocytes use SCFAs, particularly butyrate, as a primary energy source, colonocytes from GF mice are energy deprived (Donohoe et al., 2011).”
BackgroundInfluentialDepression in cancer: The many biobehavioral pathways driving tumor progression
Bortolato, B., Hyphantis, T. N., Valpione, S., Perini, G., Maes, M. H. J., Morris, G., Kubera, M., Köhler, C. A., Fernandes, B. S., Stubbs, B., et al. (2016) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2016.11.004 · Cited by 399
“Butyrate and acetate, which are fermentation products from dietary fibers metabolized by gut microbiota exert anti-inflammatory activity and regulate the infiltration of macrophages [143].”
BackgroundSinghal, R., & Shah, Y. M. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.011188 · Cited by 401
Sanchez, H. N., Moroney, J. B., Gan, H., Shen, T., Im, J. L., Li, T., Taylor, J. R., Zan, H., & Casali, P. (2020) · Nature Communications · doi:10.1038/s41467-019-13603-6 · Cited by 369
Butyrate in Energy Metabolism: There Is Still More to Learn
Zhang, L., Liu, C.-D., Jiang, Q., & Yin, Y. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2020.12.003 · Cited by 379
Metadata
- 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.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 13
- Issue
- 5
- Pages
- 517-526
- ISSN
- 1550-4131 (ISSN-L)
- 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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