The role of short chain fatty acids in health and disease

Tan, Jian; McKenzie, Craig; Potamitis, Maria; Thorburn, Alison N.; Mackay, Charles R.; Macia, Laurence

doi:10.1016/b978-0-12-800100-4.00003-9

Cited by 2,425Gut microbiota and healthGastrointestinal motility and disordersProbiotics and Fermented Foods

The role of short chain fatty acids in health and disease

Tan, Jian, McKenzie, Craig, Potamitis, Maria, Thorburn, Alison N., Mackay, Charles R., Macia, Laurence·2014·Advances in immunology

DOI 10.1016/b978-0-12-800100-4.00003-9

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Abstract

There is now an abundance of evidence to show that short-chain fatty acids (SCFAs) play an important role in the maintenance of health and the development of disease. SCFAs are a subset of fatty acids that are produced by the gut microbiota during the fermentation of partially and nondigestible polysaccharides. The highest levels of SCFAs are found in the proximal colon, where they are used locally by enterocytes or transported across the gut epithelium into the bloodstream. Two major SCFA signaling mechanisms have been identified, inhibition of histone deacetylases (HDACs) and activation of G-protein-coupled receptors (GPCRs). Since HDACs regulate gene expression, inhibition of HDACs has a vast array of downstream consequences. Our understanding of SCFA-mediated inhibition of HDACs is still in its infancy. GPCRs, particularly GPR43, GPR41, and GPR109A, have been identified as receptors for SCFAs. Studies have implicated a major role for these GPCRs in the regulation of metabolism, inflammation, and disease. SCFAs have been shown to alter chemotaxis and phagocytosis; induce reactive oxygen species (ROS); change cell proliferation and function; have anti-inflammatory, antitumorigenic, and antimicrobial effects; and alter gut integrity. These findings highlight the role of SCFAs as a major player in maintenance of gut and immune homeostasis. Given the vast effects of SCFAs, and that their levels are regulated by diet, they provide a new basis to explain the increased prevalence of inflammatory disease in Westernized countries, as highlighted in this chapter.

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Several brain disorders have been linked to imbalances in the microbial composition of the gut.
“several brain disorders have been linked to imbalances in the microbial composition of the gut (17, 19, 29, 33–37)”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [19]
Altered short-chain fatty acid production has been demonstrated in a variety of neuropathologies.
“altered SCFA production has been demonstrated in a variety of neuropathologies (19, 21, 33–35).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [19]
The microbiota is altered in CNS diseases, which aggravates the condition, and/or its modulation might prevent or improve the development and progression of CNS pathologies.
“The central hypothesis is supported by experimental and clinical evidence that the microbiota is altered in such diseases, which aggravates the condition, and/or its modulation might prevent or improve the development and progression of CNS pathologies (17, 19, 29, 33–37).”
From The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020) · cites this paper as [19]
Short-chain fatty acids are produced by the gut microbiota when undigested polysaccharides are fermented.
“SCFA are produced by the intestinal microbiota during fermentation of undigested polysaccharides.48”
From High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome (2016) · cites this paper as [48]
Altered SCFA production is demonstrated in a variety of neuropathologies.
“Altered SCFA production has also been demonstrated in a variety of neuropathologies (42, 116, 127, 130, 132, 292–295).”
From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [130]

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Inulin-type fructans with prebiotic properties counteract GPR43 overexpression and PPARγ-related adipogenesis in the white adipose tissue of high-fat diet-fed mice
Dewulf, E. M., Cani, P. D., Neyrinck, A. M., Possemiers, S., Holle, A. V., Muccioli, G. G., Deldicque, L., Bindels, L. B., Pachikian, B. D., Sohet, F. M., et al. (2010) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2010.05.009 · Cited by 269 · see citing works
Defining and analyzing geoepidemiology and human autoimmunity
Shapira, Y., Agmon‐Levin, N., & Shoenfeld, Y. (2010) · Journal of Autoimmunity · doi:10.1016/j.jaut.2009.11.018 · Cited by 262 · see citing works
Short-Chain Fatty Acids in Germfree Mice and Rats
Høverstad, T., & Midtvedt, T. (1986) · Journal of Nutrition · doi:10.1093/jn/116.9.1772 · Cited by 256 · see citing works
Microflora‐associated characteristics in faeces from allergic and nonallergic infants
Böttcher, M. F., Nordin, E. K., Sandin, A., Midtvedt, T., & Björkstén, B. (2000) · Clinical & Experimental Allergy · doi:10.1046/j.1365-2222.2000.00982.x · Cited by 256 · see citing works
Free fatty acid receptor 2 and nutrient sensing: a proposed role for fibre, fermentable carbohydrates and short-chain fatty acids in appetite regulation
Sleeth, M., Thompson, E. L., Ford, H. E., Zac‐Varghese, S., & Frost, G. S. (2010) · Nutrition Research Reviews · doi:10.1017/s0954422410000089 · Cited by 251 · see citing works
Stoichiometric and energetic analyses of non-photosynthetic CO2-fixation pathways to support synthetic biology strategies for production of fuels and chemicals
Fast, A. G., & Papoutsakis, E. T. (2012) · Current Opinion in Chemical Engineering · doi:10.1016/j.coche.2012.07.005 · Cited by 247 · see citing works
Butyrate and propionate induced activated or non-activated neutrophil apoptosis via HDAC inhibitor activity but without activating GPR-41/GPR-43 pathways
Aoyama, M., Kotani, J., & Usami, M. (2009) · Nutrition · doi:10.1016/j.nut.2009.07.006 · Cited by 246 · see citing works
Oral butyrate for mildly to moderately active Crohn's disease
Sabatino, A. D., Morera, R., Ciccocioppo, R., Cazzola, P., GOTTI, S., Tinozzi, F. P., Tinozzi, S., & Corazza, G. R. (2005) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2005.02639.x · Cited by 245 · see citing works
Tight junctions at a glance
Balda, M. S., & Matter, K. (2008) · Journal of Cell Science · doi:10.1242/jcs.023887 · Cited by 235 · see citing works
Butyric acid-based feed additives help protect broiler chickens from Salmonella Enteritidis infection
Fernández-Rubio, C., Ordóñez, C., González, J. I. A., Gallego, A. G., Honrubia, M. P., Mallo, J. J., & Balaña‐Fouce, R. (2009) · Poultry Science · doi:10.3382/ps.2008-00484 · Cited by 233 · see citing works
The Microbiome and Inflammatory Bowel Disease: Is There a Therapeutic Role for Fecal Microbiota Transplantation?
Damman, C. J., Miller, S. I., Surawicz, C. M., & Zisman, T. L. (2012) · The American Journal of Gastroenterology · doi:10.1038/ajg.2012.93 · Cited by 224 · see citing works
Microbial influences on epithelial integrity and immune function as a basis for inflammatory diseases
Macia, L., Thorburn, A. N., Binge, L. C., Mariño, E., Rogers, K. E., Maslowski, K. M., Vieira, A. T., Kranich, J., & Mackay, C. R. (2011) · Immunological Reviews · doi:10.1111/j.1600-065x.2011.01080.x · Cited by 223 · see citing works
Self-citation
Short-chain fatty acids stimulate the migration of neutrophils to inflammatory sites
Vinolo, M. A. R., Rodrigues, H. G., Hatanaka, E., Hebeda, C. B., Farsky, S. H. P., & Curi, R. (2009) · Clinical Science · doi:10.1042/cs20080642 · Cited by 209 · see citing works
Propionate. Anti-obesity and satiety enhancing factor?
Arora, T., Sharma, R., & Frost, G. (2011) · Appetite · doi:10.1016/j.appet.2011.01.016 · Cited by 205 · see citing works
Gut permeability and food allergies
Perrier, C., & Corthésy, B. (2010) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2010.03639.x · Cited by 203 · see citing works
SLC5A8 (SMCT1)-mediated transport of butyrate forms the basis for the tumor suppressive function of the transporter
Gupta, N., Martin, P. M., Prasad, P. D., & Ganapathy, V. (2005) · Life Sciences · doi:10.1016/j.lfs.2005.10.028 · Cited by 190 · see citing works
Acetate, the Key Modulator of Inflammatory Responses in Acute Alcoholic Hepatitis
Kendrick, S. F. W., O’Boyle, G., Mann, J., Zeybel, M., Palmer, J. M., Jones, D. E. J., & Day, C. (2010) · Hepatology · doi:10.1002/hep.23572 · Cited by 169 · see citing works
Cellular expression of monocarboxylate transporters (MCT) in the digestive tract of the mouse, rat, and humans, with special reference to slc5a8.
Iwanaga, T., Takebe, K., Kato, I., Karaki, S.-I., & Kuwahara, A. (2006) · Biomedical research · doi:10.2220/biomedres.27.243 · Cited by 161 · see citing works
Prebiotic oligosaccharides change the concentrations of short-chain fatty acids and the microbial population of mouse bowel
Pan, X.-D., Chen, F., Wu, T., Tang, H., & Zhao, Z.-Y. (2009) · Journal of Zhejiang University SCIENCE B · doi:10.1631/jzus.b0820261 · Cited by 160 · see citing works
Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression
Soliman, M. L., & Rosenberger, T. A. (2011) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-011-0751-3 · Cited by 158 · see citing works
Regulation of virulence by butyrate sensing in enterohaemorrhagic Escherichia coli
Nakanishi, N., Tashiro, K., Kuhara, S., Hayashi, T., Sugimoto, N., & Tobe, T. (2009) · Microbiology · doi:10.1099/mic.0.023499-0 · Cited by 156 · see citing works
Modulation of Antimicrobial Host Defense Peptide Gene Expression by Free Fatty Acids
Sunkara, L. T., Jiang, W., & Zhang, G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049558 · Cited by 140 · see citing works
Oral Supplementation of Butyrate Reduces Mucositis and Intestinal Permeability Associated with 5‐Fluorouracil Administration
Ferreira, T. M. R., Leonel, A. J., de Melo, M. A. B., Santos, R. R. G., Cara, D. C., Cardoso, V. N., Correia, M. I. T. D., & Alvarez-Leite, J. I. (2012) · Lipids · doi:10.1007/s11745-012-3680-3 · Cited by 138 · see citing works
Histone/protein deacetylase inhibitors increase suppressive functions of human FOXP3+ Tregs
Akimova, T., Ge, G., Golovina, T. N., Mikheeva, T., Wang, L., Riley, J. L., & Hancock, W. W. (2010) · Clinical Immunology · doi:10.1016/j.clim.2010.04.018 · Cited by 133 · see citing works
Histone deacetylase inhibitor, butyrate, attenuates lipopolysaccharide-induced acute lung injury in mice
Ni, Y., Wang, J., Yan, X., Tian, F., Zhao, J., Wang, Y., & Jiang, T. (2010) · Respiratory Research · doi:10.1186/1465-9921-11-33 · Cited by 133 · see citing works
Sodium butyrate up-regulates cathelicidin gene expression via activator protein-1 and histone acetylation at the promoter region in a human lung epithelial cell line, EBC-1
Kida, Y., SHIMIZU, T., & Kuwano, K. (2006) · Molecular Immunology · doi:10.1016/j.molimm.2005.11.014 · Cited by 118 · see citing works
Histone acetylation: Where to go and how to get there
MacDonald, V. E., & Howe, L. J. (2009) · Epigenetics · doi:10.4161/epi.4.3.8484 · Cited by 116 · see citing works
A Novel Antiinflammatory Role for the Short-Chain Fatty Acids in Human Labor
Voltolini, C., Battersby, S., McHaffie, S. L., Petraglia, F., Norman, J. E., & Jabbour, H. N. (2011) · Endocrinology · doi:10.1210/en.2011-1457 · Cited by 105 · see citing works
Biological functions of SLC5A8, a candidate tumour suppressor
Ganapathy, V., Gopal, E., Miyauchi, S., et al. (2005) · Biochemical Society Transactions · doi:10.1042/bst0330237 · Cited by 103 · see citing works
Short chain fatty acids (propionic and hexanoic) decrease Staphylococcus aureus internalization into bovine mammary epithelial cells and modulate antimicrobial peptide expression
Alva-Murillo, N., Ochoa‐Zarzosa, A., & López-Meza, J. E. (2011) · Veterinary Microbiology · doi:10.1016/j.vetmic.2011.08.025 · Cited by 99 · see citing works
A novel nutrient sensing mechanism underlies substrate-induced regulation of monocarboxylate transporter-1
Borthakur, A., Priyamvada, S., Kumar, A., Anbazhagan, A. N., Gill, R. K., Alrefai, W. A., & Dudeja, P. K. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00308.2012 · Cited by 98 · see citing works
Cytoplasmic IκBα Increases NF-κB-independent Transcription through Binding to Histone Deacetylase (HDAC) 1 and HDAC3
Viatour, P., Legrand-Poels, S., Lint, C. M. V., Warnier, M., Merville, M., GIELEN, J. E., Piette, J. G., Bours, V., & Chariot, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306381200 · Cited by 95 · see citing works
Differences in risk of Crohn's disease in offspring of mothers and fathers with inflammatory bowel disease.
Akolkar, P. N., Gulwani-Akolkar, B., Heresbach, D., Lin, X., Fisher, S. A., Katz, S., & Silver, J. E. (1997) · PubMed · Cited by 93 · see citing works
Progress in genomics, metabolism and biotechnology of bifidobacteria
Cronin, M. A., Ventura, M., Fitzgerald, G. F., & van Sinderen, D. (2011) · International Journal of Food Microbiology · doi:10.1016/j.ijfoodmicro.2011.01.019 · Cited by 92 · see citing works
Induction of Foxp3+ regulatory T cells with histone deacetylase inhibitors
Lucas, J. L., Mirshahpanah, P., Haas-Stapleton, E. J., Asadullah, K., Zollner, T. M., & Numerof, R. P. (2009) · Cellular Immunology · doi:10.1016/j.cellimm.2009.03.004 · Cited by 91 · see citing works
Activation of Motility by Sensing Short-Chain Fatty Acids via Two Steps in a Flagellar Gene Regulatory Cascade in Enterohemorrhagic Escherichia coli
Tobe, T., Nakanishi, N., & Sugimoto, N. (2010) · Infection and Immunity · doi:10.1128/iai.00927-10 · Cited by 90 · see citing works
Effects of high fat diet on GPR109A and GPR81 gene expression
Wanders, D., Graff, E. C., & Judd, R. L. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.07.082 · Cited by 89 · see citing works
LSSIG is a novel murine leukocyte-specific GPCR that is induced by the activation of STAT3
Senga, T., Iwamoto, S., Yoshida, T., Yokota, T., Adachi, K., Azuma, E., Hamaguchi, M., & Iwamoto, T. (2003) · Blood · doi:10.1182/blood-2002-06-1881 · Cited by 86 · see citing works
HDAC2 deacetylates class II transactivator and suppresses its activity in macrophages and smooth muscle cells
Kong, X., Fang, M., Li, P., et al. (2008) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2008.10.023 · Cited by 83 · see citing works
Butyrate-induced GPR41 Activation Inhibits Histone Acetylation and Cell Growth
Wu, J., Zhou, Z., Hu, Y., & Dong, S. (2012) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2012.05.008 · Cited by 81 · see citing works
The interaction of short-chain fatty acids with adipose tissue: relevance for prevention of type 2 diabetes
Roelofsen, H., Priebe, M., & Vonk, R. (2010) · Beneficial Microbes · doi:10.3920/bm2010.0028 · Cited by 80 · see citing works
Intestinal permeability is increased in bronchial asthma
Hijazi, Z. (2004) · Archives of Disease in Childhood · doi:10.1136/adc.2003.027680 · Cited by 79 · see citing works
Mixtures of SCFA, composed according to physiologically available concentrations in the gut lumen, modulate histone acetylation in human HT29 colon cancer cells
Kiefer, J., Beyer-Sehlmeyer, G., & Pool-Zobel, B. L. (2006) · British Journal Of Nutrition · doi:10.1017/bjn20061948 · Cited by 74 · see citing works
HDAC7 Is a Repressor of Myeloid Genes Whose Downregulation Is Required for Transdifferentiation of Pre-B Cells into Macrophages
Barneda‐Zahonero, B., Román-González, L., Collazo, O., Rafati, H., Islam, A. B. M. M. K., Bussmann, L. H., Tullio, A. D., de Andrés-Aguayo, L., Graf, T., López-Bigas, N., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003503 · Cited by 67 · see citing works
Review: Free fatty acid receptors: emerging targets for treatment of diabetes and its complications
Kennedy, R. L., Vangaveti, V., Jarrod, G., Shashidhar, V., Shashidhar, V., & Baune, B. T. (2010) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/2042018810381066 · Cited by 67 · see citing works
Fecal transplantation for the treatment of Clostridium difficile infection.
Brandt, L. J. (2012) · PubMed · Cited by 66 · see citing works
Role of HDAC3 on p53 Expression and Apoptosis in T Cells of Patients with Multiple Sclerosis
Zhang, F., Shi, Y., Wang, L. H.-C., & Sriram, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016795 · Cited by 59 · see citing works
Differential effects of short-chain fatty acids and iron on expression of iha in Shiga-toxigenic Escherichia coli
Herold, S., Paton, J. C., Srimanote, P., & Paton, A. W. (2009) · Microbiology · doi:10.1099/mic.0.029454-0 · Cited by 54 · see citing works
Interleukin-12 p40 promoter activity is regulated by the reversible acetylation mediated by HDAC1 and p300
Lü, J., Sun, H., Wang, X., et al. (2005) · Cytokine · doi:10.1016/j.cyto.2005.03.001 · Cited by 51 · see citing works
Modulation of HDL metabolism by the niacin receptor GPR109A in mouse hepatocytes
Li, X., Millar, J. S., Brownell, N. K., Briand, F., & Rader, D. J. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.07.023 · Cited by 51 · see citing works
Evaluation of the relationship between GPR43 and adiposity in human
Dewulf, E. M., Ge, Q., Bindels, L. B., Sohet, F. M., Cani, P. D., Brichard, S. M., & Delzenne, N. M. (2013) · Nutrition & Metabolism · doi:10.1186/1743-7075-10-11 · Cited by 51 · see citing works
Reduction of telomerase activity in human liver cancer cells by a histone deacetylase inhibitor
Nakamura, M., Saito, H., Ebinuma, H., Wakabayashi, K., Saito, Y., Takagi, T., Nakamoto, N., & Ishii, H. (2001) · Journal of Cellular Physiology · doi:10.1002/jcp.1087 · Cited by 44 · see citing works
Acetate Production by Methanogenic Bacteria
Westermann, P., Ahring, B. K., & Mah, R. A. (1989) · Applied and Environmental Microbiology · doi:10.1128/aem.55.9.2257-2261.1989 · Cited by 41 · see citing works
Butyrate and Type 1 Diabetes Mellitus: Can We Fix the Intestinal Leak?
Li, N., Hatch, M., Wasserfall, C. H., et al. (2010) · Journal of Pediatric Gastroenterology and Nutrition · doi:10.1097/mpg.0b013e3181dd913a · Cited by 40 · see citing works
Effects of Nicotinic Acid on Gene Expression: Potential Mechanisms and Implications for Wanted and Unwanted Effects of the Lipid-Lowering Drug
Kang, I., Kim, S., & Youn, J. H. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1104 · Cited by 39 · see citing works
n‐Butyrate Anergized Effector CD4+ T Cells Independent of Regulatory T cell Generation or Activity
FONTENELLE, B. M., & Gilbert, K. M. (2012) · Scandinavian Journal of Immunology · doi:10.1111/j.1365-3083.2012.02740.x · Cited by 32 · see citing works
Nicotinic Acid Receptor Abnormalities in Human Skin Cancer: Implications for a Role in Epidermal Differentiation
Bermudez, Y., Benavente, C. A., Meyer, R. G., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020487 · Cited by 31 · see citing works
Gene expression associated with the decrease in malignant phenotype of human liver cancer cells following stimulation with a histone deacetylase inhibitor
Wakabayashi, K., Saito, H., Kaneko, F., et al. (2005) · International Journal of Oncology · doi:10.3892/ijo.26.1.233 · Cited by 30 · see citing works
Fecal microbiota transplantation: a new standard treatment option forClostridium difficileinfection
Borody, T. J., Brandt, L. J., Paramsothy, S., & Agrawal, G. K. (2013) · Expert Review of Anti-infective Therapy · doi:10.1586/eri.13.26 · Cited by 24 · see citing works
Niacin inhibits skin dendritic cell mobilization in a GPR109A independent manner but has no impact on monocyte trafficking in atherosclerosis
Ingersoll, M. A., Potteaux, S., Álvarez, D., Hutchison, S. B., van Rooijen, N., & Randolph, G. J. (2011) · Immunobiology · doi:10.1016/j.imbio.2011.05.014 · Cited by 11 · see citing works

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Pathophysiology of type 2 diabetes mellitus
Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K. B., Ostolaza, H., & Martín, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176275 · Cited by 3,360 · see citing works
The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication
Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.00025 · Cited by 3,043 · see citing works
Control of adaptive immunity by the innate immune system
Iwasaki, A., & Medzhitov, R. (2015) · Nature Immunology · doi:10.1038/ni.3123 · Cited by 2,160 · see citing works
High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome
De Filippis, F., Pellegrini, N., Vannini, L., Jeffery, I. B., La Storia, A., Laghi, L., Serrazanetti, D. I., Di Cagno, R., Ferrocino, I., Lazzi, C., et al. (2016) · Gut · doi:10.1136/gutjnl-2015-309957 · Cited by 1,638 · see citing works
Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome
Macia, L., Tan, J., Vieira, A. T., Leach, K., Stanley, D., Luong, S., Maruya, M., Ian McKenzie, C., Hijikata, A., Wong, C., et al. (2015) · Nature Communications · doi:10.1038/ncomms7734 · Cited by 1,439 · see citing works
Self-citation
High-Fiber Diet and Acetate Supplementation Change the Gut Microbiota and Prevent the Development of Hypertension and Heart Failure in Hypertensive Mice
Marques, F. Z., Nelson, E., Chu, P.-Y., Horlock, D., Fiedler, A., Ziemann, M., Tan, J. K., Kuruppu, S., Rajapakse, N. W., El-Osta, A., et al. (2017) · Circulation · doi:10.1161/circulationaha.116.024545 · Cited by 1,065 · see citing works
Self-citation
Diet, metabolites, and “western-lifestyle” inflammatory diseases
Thorburn, A. N., Macia, L., & Mackay, C. R. (2014) · Immunity · doi:10.1016/j.immuni.2014.05.014 · Cited by 879 · see citing works
Self-citation
Gut microbiota-derived short-chain Fatty acids, T cells, and inflammation
Kim, C. H., Park, J., & Kim, M. (2014) · Immune Network · doi:10.4110/in.2014.14.6.277 · Cited by 704 · see citing works
Dietary fibre modulates the gut microbiota
Cronin, P., Joyce, S. A., O’Toole, P. W., & O’Connor, E. M. (2021) · Nutrients · doi:10.3390/nu13051655 · Cited by 658 · see citing works
Short chain fatty acids prevent high-fat-diet-induced obesity in mice by regulating g protein-coupled receptors and gut microbiota
Lu, Y., Fan, C., Li, P., Lu, Y., Chang, X., & Qi, K. (2016) · Scientific Reports · doi:10.1038/srep37589 · Cited by 638 · see citing works
The Gut Microbiome and the Brain
Galland, L. (2014) · Journal of Medicinal Food · doi:10.1089/jmf.2014.7000 · Cited by 648 · see citing works
Diet-Microbiota Interactions Mediate Global Epigenetic Programming in Multiple Host Tissues
Krautkramer, K. A., Kreznar, J. H., Romano, K. A., Vivas, E. I., Barrett-Wilt, G. A., Rabaglia, M. E., Keller, M. P., Attie, A. D., Rey, F. E., & Denu, J. M. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.10.025 · Cited by 607 · see citing works
Collective unconscious: How gut microbes shape human behavior
Dinan, T. G., Stilling, R. M., Stanton, C., & Cryan, J. F. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.02.021 · Cited by 571 · see citing works
Microbiome–microglia connections via the gut–brain axis
Abdel-Haq, R., Schlachetzki, J. C. M., Glass, C. K., & Mazmanian, S. K. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20180794 · Cited by 471 · see citing works
“McGeer et al., 1988; Akiyama and McGeer, 1989; Gerhard et al., 2006; Kim and Joh, 2006; Watson et al., 2012; Fasano et al., 2013; Tan et al., 2014a; Keshavarzian et al., 2015; Scheperjans et al., 2015; Machado et al., 2016; Poirier et al., 2016; Sampson et al., 2016; Unger et al., 2016; Zhang et…”
BackgroundInfluential
Dietary supplementation with inulin-propionate ester or inulin improves insulin sensitivity in adults with overweight and obesity with distinct effects on the gut microbiota, plasma metabolome and systemic inflammatory responses: A randomised cross-over trial
Chambers, E. S., Byrne, C. S., Morrison, D. J., Murphy, K. G., Preston, T., Tedford, C., Garcia-Perez, I., Fountana, S., Serrano-Contreras, J. I., Holmes, E., et al. (2019) · Gut · doi:10.1136/gutjnl-2019-318424 · Cited by 443 · see citing works
The progress of gut microbiome research related to brain disorders
Zhu, S., Jiang, Y., Xu, K., Cui, M., Ye, W., Zhao, G., Jin, L., & Chen, X. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-1705-z · Cited by 419 · see citing works
The effect of short-chain fatty acids on human monocyte-derived dendritic cells
Nastasi, C., Candela, M., Bonefeld, C. M., Geisler, C., Hansen, M., Krejsgaard, T., Biagi, E., Andersen, M. H., Brigidi, P., Ødum, N., et al. (2015) · Scientific Reports · doi:10.1038/srep16148 · Cited by 414 · see citing works
Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis
Rusch, J. A., Layden, B. T., & Dugas, L. R. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1130689 · Cited by 415 · see citing works
Complex regulatory effects of gut microbial short-chain fatty acids on immune tolerance and autoimmunity
Kim, C. H. (2023) · Cellular & Molecular Immunology · doi:10.1038/s41423-023-00987-1 · Cited by 420 · see citing works
Update on lactose malabsorption and intolerance: pathogenesis, diagnosis and clinical management
Misselwitz, B., Butter, M., Verbeke, K., & Fox, M. R. (2019) · Gut · doi:10.1136/gutjnl-2019-318404 · Cited by 390 · see citing works
Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism
Fachi, J. L., Felipe, J. D. S., Pral, L. P., da Silva, B. K., Corrêa, R. O., de Andrade, M. C. P., da Fonseca, D. M., Basso, P. J., Câmara, N. O. S., de Sales e Souza, É. L., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.03.054 · Cited by 364 · see citing works
Microbiome-modulated metabolites at the interface of host immunity
Blacher, E., Levy, M., Tatirovsky, E., & Elinav, E. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601247 · Cited by 354 · see citing works
Connecting the immune system, systemic chronic inflammation and the gut microbiome: the role of sex
Rizzetto, L., Fava, F., Tuohy, K. M., & Selmi, C. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.05.008 · Cited by 331 · see citing works
Short-chain fatty acids (SCFAs) alone or in combination regulate select immune functions of microglia-like cells
Wenzel, T. J., Gates, E. J., Ranger, A. L., & Klegeris, A. (2020) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2020.103493 · Cited by 320 · see citing works
The neuroendocrinology of the microbiota-gut-brain axis: a behavioural perspective
Cussotto, S., Sandhu, K. V., Dinan, T. G., & Cryan, J. F. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.04.002 · Cited by 326 · see citing works
“The free SCFAs are also able to cross the blood-brain barrier (BBB) through monocarboxylate transporters and act in several brain regions (Tan et al., 2014).”
Background
Gut bacteria signaling to mitochondria in intestinal inflammation and cancer
Jackson, D. N., & Theiss, A. L. (2020) · Gut Microbes · doi:10.1080/19490976.2019.1592421 · Cited by 312 · see citing works
Modulation of Gut Microbiota–Brain Axis by Probiotics, Prebiotics, and Diet
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Authors: Tan, J., McKenzie, C., Potamitis, M., Thorburn, A. N., Mackay, C. R., & Macia, L.
Affiliations: Monash University (AU)
Corresponding author: Mackay, Charles R.
Macia, Laurence
ORCID: McKenzie, Craig
Mackay, Charles R.
Macia, Laurence
Venue: Advances in immunology
Publisher: Elsevier
Published: 2014
Volume: 121
Pages: 91-119
ISSN: 0065-2776 (ISSN-L)
DOI: 10.1016/b978-0-12-800100-4.00003-9
OpenAlex: W1948266836
Cited by: 2,425
References: 134
Citations by year: 2026: 195 · 2025: 269 · 2024: 307 · 2023: 312 · 2022: 369 · 2021: 270 · 2020: 214 · 2019: 164 · 2018: 117 · 2017: 79 · 2016: 55 · 2015: 45 · 2014: 23
FWCI: 85.17
Type: book chapter
Language: en
Open access: closed
Locations: Advances in immunology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Keywords: short-chain fatty acids, gut microbiota, histone deacetylase inhibition, G protein-coupled receptors, GPR43, GPR41, GPR109A, colonic fermentation, intestinal epithelium, inflammation, immune homeostasis, chemotaxis, phagocytosis, reactive oxygen species, anti-tumorigenic effects, antimicrobial activity, intestinal barrier integrity, diet
MeSH terms: Animals, Fatty Acids, Volatile, Humans, Inflammation, Receptors, Nicotinic, Substrate Specificity, Signal Transduction, Cytokines, Receptors, G-Protein-Coupled, Histone Deacetylase Inhibitors, Microbiota

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The role of short chain fatty acids in health and disease

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