短链脂肪酸在肠道中生理作用的研究进展
Research Progress of Physiological Function of Short-Chain Fatty Acids in the Intestine
摘要: 短链脂肪酸是肠道菌群的主要代谢产物,其在人体的消化、免疫、内分泌、心血管、神经等多个系统中起着重要作用,因其产生及转运主要发生在肠道中,故其在肠道中的生理作用十分重要。故本文将就短链脂肪酸在肠道中的生理作用作一综述。
Abstract: Short-chain fatty acids are the main metabolites of the intestinal flora. They play an important role in the digestion, immunity, endocrine, cardiovascular, and nervous systems of the human body. Because their production and transport mainly occur in the intestine, the physiological role in the intestine is very important. Therefore, this article will review the physiological role of short-chain fatty acids in the intestinal tract.
文章引用:殷桐, 包蕾. 短链脂肪酸在肠道中生理作用的研究进展[J]. 临床医学进展, 2022, 12(2): 939-945. https://doi.org/10.12677/ACM.2022.122137

参考文献

[1] Huda-Faujan, N., Abdulamir, A.S., Fatimah, A.B., et al. (2010) The Impact of the Level of the Intestinal Short Chain Fatty Acids in Inflammatory Bowel Disease Patients versus Healthy Subjects. The Open Biochemistry Journal, 4, 53-58. [Google Scholar] [CrossRef
[2] Gonçalves, P. and Martel, F. (2016) Regulation of Colonic Epithelial Butyrate Transport: Focus on Colorectal Cancer. Porto Biomedical Journal, 1, 83-91. [Google Scholar] [CrossRef] [PubMed]
[3] den Besten, G., van Eunen, K., Groen, A.K., Venema, K., Reijngoud, D.-J. and Bakker, B.M. (2013) The Role of Short-Chain Fatty Acids in the Interplay between Diet, Gut Microbiota, and Host Energy Metabolism. Journal of lipid research, 54, 2325-2340. [Google Scholar] [CrossRef
[4] Nogal, A., Valdes, A.M. and Menni, C. (2021) The Role of Short-Chain Fatty Acids in the Interplay between Gut Microbiota and Diet in Cardio-Metabolic Health. Gut Microbes, 13, Article ID: 1897212. [Google Scholar] [CrossRef] [PubMed]
[5] Tan, J., McKenzie, C., Vuillermin, P.J., Goverse, G., Vinuesa, C.G., Mebius, R.E., Macia, L. and Mackay, C.R. (2016) Dietary Fiber and Bacterial SCFA Enhance Oral Tolerance and Protect against Food Allergy through Diverse Cellular Pathways. Cell Reports, 15, 2809-2824. [Google Scholar] [CrossRef] [PubMed]
[6] Caroline, R., Remo, F., Ruth, F., Susanne, L., Patrick, W., Claudio, R., et al. (2019) High Levels of Butyrate and Propionate in Early Life Are Associated with Protection against Atopy. Allergy, 74, 799-809.
[7] Richards, L.B., Li, M., Esch, B.V., Garssen, J. and Folkerts, G. (2016) The Effects of Short-Chain Fatty Acids on the Cardiovascular System. Pharmanutrition, 4, 68-111. [Google Scholar] [CrossRef
[8] Miller, T.L. and Wolin, M.J. (1996) Pathways of Acetate, Propionate, and Butyrate Formation by the Human Fecal Microbial Flora. Applied and Environmental Microbiology, 62, 1589-1592. [Google Scholar] [CrossRef] [PubMed]
[9] Niccolai, E., Baldi, S., Ricci, F., Russo, E., Nannini, G., Menicatti, M., et al. (2019) Evaluation and Comparison of Short Chain Fatty Acids Composition in Gut Diseases. World Journal of Gastroenterology, 25, 5543-5558. [Google Scholar] [CrossRef] [PubMed]
[10] Rooks, M.G. and Garrett, W.S. (2016) Gut Microbiota, Metabolites and Host Immunity. Nature Reviews. Immunology, 16, 341-352. [Google Scholar] [CrossRef] [PubMed]
[11] Hamer, H.M., Jonkers, D., Venema, K., Vanhoutvin, S., Troost, F.J. and Brummer, R.J. (2008) Review Article: The Role of Butyrate on Colonic Function. Alimentary Pharmacology & Therapeutics, 27, 104-119. [Google Scholar] [CrossRef] [PubMed]
[12] Bridgman, S.L., Azad, M.B., Field, C.J., Haqq, A.M., Becker, A.B., Mandhane, P.J., et al. (2017) Fecal Short-Chain Fatty Acid Variations by Breastfeeding Status in Infants at 4 Months: Differences in Relative versus Absolute Concentrations. Frontiers in Nutrition, 4, Article No. 11. [Google Scholar] [CrossRef] [PubMed]
[13] Tsukuda, N., Yahagi, K., Hara, T., Watanabe, Y., Matsumoto, H., Mori, H., et al. (2021) Key Bacterial Taxa and Metabolic Pathways Affecting Gut Short-Chain Fatty Acid Profiles in Early Life. The ISME Journal, 15, 2574-2590. [Google Scholar] [CrossRef] [PubMed]
[14] Pourcyrous, M., Nolan, V.G., Goodwin, A., Davis, S.L. and Buddington, R.K. (2014) Fecal Short-Chain Fatty Acids of Very-Low-Birth-Weight Preterm Infants Fed Expressed Breast Milk or Formula. Journal of Pediatric Gastroenterology and Nutrition, 59, 725-731. [Google Scholar] [CrossRef
[15] Furusawa, Y., Obata, Y., Fukuda, S., Endo, T.A., Nakato, G., Takahashi, D., et al. (2013) Commensal Microbe-Derived Butyrate Induces the Differentiation of Colonic Regulatory T Cells. Nature, 504, 446-450. [Google Scholar] [CrossRef] [PubMed]
[16] Priyadarshini, M., Kotlo, K.U., Dudeja, P.K. and Layden, B.T. (2018) Role of Short Chain Fatty Acid Receptors in Intestinal Physiology and Pathophysiology. Comprehensive Physiology, 8, 1091-1115. [Google Scholar] [CrossRef] [PubMed]
[17] Smith, P.M., Howitt, M.R., Panikov, N., Michaud, M., Gallini, C.A., Bohlooly-Y, M., et al. (2013) The Microbial Metabolites, Short-Chain Fatty Acids, Regulate Colonic Treg Cell Homeostasis. Science, 341, 569-573. [Google Scholar] [CrossRef] [PubMed]
[18] Tan, J., Mckenzie, C., Potamitis, M., Thorburn, A.N., Mackay, C.R. and Macia, L. (2014) The Role of Short-Chain Fatty Acids in Health and Disease. Advances in Immunology, 21, 91-119. [Google Scholar] [CrossRef
[19] Yao, Y., Cai, X., Fei, W., Ye, Y., Zhao, M. and Zheng, C. (2022) The Role of Short-Chain Fatty Acids in Immunity, Inflammation and Metabolism. Critical Reviews in Food Science and Nutrition, 62, 1-12. [Google Scholar] [CrossRef] [PubMed]
[20] Wang, N., Guo, D.Y., Tian, X., Lin, H.P., Li, Y.P., Chen, S.J., et al. (2016) Niacin Receptor GPR109A Inhibits Insulin Secretion and Is Down-Regulated in Type 2 Diabetic Islet Beta-Cells. General & Comparative Endocrinology, 237, 98-108. [Google Scholar] [CrossRef] [PubMed]
[21] Luu, M., Pautz, S., Kohl, V., Singh, R., Romero, R., Lucas, S., et al. (2019) The Short-Chain Fatty Acid Pentanoate Suppresses Autoimmunity by Modulating the Metabolic-Epigenetic Crosstalk in Lymphocytes. Nature Communications, 10, Article No. 760.
[22] Zheng, N., Gao, Y., Zhu, W., Meng, D. and Walker, W.A. (2020) Short Chain Fatty Acids Produced by Colonizing Intestinal Commensal Bacterial Interaction with Expressed Breast Milk Are Anti-Inflammatory in Human Immature Enterocytes. PLoS ONE, 15, e0229283. [Google Scholar] [CrossRef] [PubMed]
[23] Chang, P.V., Hao, L., Offermanns, S. and Medzhitov, R. (2014) The Microbial Metabolite Butyrate Regulates Intestinal Macrophage Function via Histone Deacetylase Inhibition. Proceedings of the National Academy of Sciences of the United States of America, 111, 2247-2252. [Google Scholar] [CrossRef] [PubMed]
[24] Vinolo, M., Rodrigues, H.G., Hatanaka, E., Sato, F.T., Sampaio, S.C. and Curi, R. (2011) Suppressive Effect of Short-Chain Fatty Acids on Production of Proinflammatory Mediators by Neutrophils. Journal of Nutritional Biochemistry, 22, 849-855. [Google Scholar] [CrossRef] [PubMed]
[25] Ni, Y.F., Wang, J., Yan, X.L., Tian, F., Zhao, J.B., Wang, Y.J., et al. (2010) Histone Deacetylase Inhibitor, Butyrate, Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Mice. Respiratory Research, 11, Article No. 33. [Google Scholar] [CrossRef] [PubMed]
[26] Maslowski, K.M. and Mackay, C.R. (2011) Diet, Gut Microbiota and Immune Responses. Nature Immunology, 12, 5-9. [Google Scholar] [CrossRef] [PubMed]
[27] Liu, J., Zhu, H., Li, B., Lee, C., Alganabi, M., Zheng, S., et al. (2020) Beneficial Effects of Butyrate in Intestinal Injury. Journal of Pediatric Surgery, 55, 1088-1093. [Google Scholar] [CrossRef] [PubMed]
[28] Joossens, M., Huys, G., Cnockaert, M., De Preter, V., Verbeke, K., Rutgeerts, P., et al. (2011) Dysbiosis of the Faecal Microbiota in Patients with Crohn’s Disease and Their Unaffected Relatives. Gut, 60, 631-637. [Google Scholar] [CrossRef] [PubMed]
[29] Morgan, X.C., Tickle, T.L., Sokol, H., Gevers, D., Devaney, K.L., Ward, D.V., et al. (2012) Dysfunction of the Intestinal Microbiome in Inflammatory Bowel Disease and Treatment. Genome biology, 13, Article No. R79. [Google Scholar] [CrossRef] [PubMed]
[30] Lin, J. (2004) Too Much Short Chain Fatty Acids Cause Neonatal Necrotizing Enterocolitis. Medical Hypotheses, 62, 291-293. [Google Scholar] [CrossRef
[31] Roy, S.K., Meng, Q., Sadowitz, B.D., Kollisch-Singule, M., Yepuri, N., Satalin, J., et al. (2018) Enteral Administration of Bacteria Fermented Formula in Newborn Piglets: A High Fidelity Model for Necrotizing Enterocolitis (NEC). PLoS ONE, 13, e0201172. [Google Scholar] [CrossRef] [PubMed]
[32] Alva-Murillo, N., Ochoa-Zarzosa, A. and López-Meza, J.E. (2012) Short Chain Fatty Acids (Propionic and Hexanoic) Decrease Staphylococcus aureus Internalization into Bovine Mammary Epithelial Cells and Modulate Antimicrobial Peptide Expression. Veterinary Microbiology, 155, 324-331. [Google Scholar] [CrossRef] [PubMed]
[33] Dewulf, E.M., Qian, G., Bindels, L.B., Sohet, F.M., Cani, P.D., Brichard, S.M., et al. (2013) Evaluation of the Relationship between GPR43 and Adiposity in Human. Nutrition & Metabolism, 10, Article No. 11. [Google Scholar] [CrossRef] [PubMed]
[34] Arora, T., Sharma, R. and Frost, G. (2011) Propionate. Anti-Obesity and Satiety Enhancing Factor? Appetite, 56, 511-515. [Google Scholar] [CrossRef] [PubMed]
[35] Sunkara, L.T., Jiang, W. and Zhang, G. (2012) Modulation of Antimicrobial Host Defense Peptide Gene Expression by Free Fatty Acids. PLoS ONE, 7, e49558. [Google Scholar] [CrossRef] [PubMed]
[36] Fernandez-Rubio, C., Ordonez, C., Abad-Gonzalez, J., Garcia-Gallego, A., Honrubia, M.P., Mallo, J.J., et al. (2009) Butyric Acid-Based Feed Additives Help Protect Broiler Chickens from Salmonella Enteritidis Infection. Poultry Science, 88, 943-948. [Google Scholar] [CrossRef] [PubMed]
[37] Roy, C.C., Kien, C.L., Bouthillier, L. and Levy, E. (2006) Short-Chain Fatty Acids: Ready for Prime Time? Nutrition in Clinical Practice, 21, 351-366. [Google Scholar] [CrossRef] [PubMed]
[38] Chiara, V., Sharon, B., Etherington, S.L., Petraglia, F., Norman, J.E. and Jabbour, H.N. (2012) A Novel Antiinflammatory Role for the Short-Chain Fatty Acids in Human Labor. Endocrinology, 153, 395-403. [Google Scholar] [CrossRef] [PubMed]
[39] Burger-van Paassen, N., Vincent, A., Puiman, P., van der Sluis, M., Bouma, J., Boehm, G., et al. (2009) The Regulation of Intestinal Mucin MUC2 Expression by Short-Chain Fatty Acids: Implications for Epithelial Protection. Biochemical Journal, 420, 211-219. [Google Scholar] [CrossRef
[40] Tolhurst, G., Heffron, H., Lam, Y.S., Parker, H.E., Habib, A.M., Diakogiannaki, E., et al. (2012) Short-Chain Fatty Acids Stimulate Glucagon-Like Peptide-1 Secretion via the G-Protein-Coupled Receptor FFAR2. Diabetes, 61, 364-371.
[41] Wang, H.B., Wang, P.Y., Wang, X., Wan, Y.-L. and Liu, Y.-C. (2012) Butyrate Enhances Intestinal Epithelial Barrier Function via Up-Regulation of Tight Junction Protein Claudin-1 Transcription. Digestive Diseases & Sciences, 57, 3126-3135. [Google Scholar] [CrossRef] [PubMed]
[42] Mirzaei, R., Afaghi, A. and Babakhani, S., Sohrabi, M.R., Hosseini-Fard, S.R., Babolhavaeji, K., et al. (2021) Role of Microbiota-Derived Short-Chain Fatty Acids in Cancer Development and Prevention. Biomedicine & Pharmacotherapy, 139, Article ID: 111619. [Google Scholar] [CrossRef] [PubMed]
[43] Carretta, M.D., Quiroga, J., López, R., Hidalgo, M.A. and Burgos, R.A. (2021) Participation of Short-Chain Fatty Acids and Their Receptors in Gut Inflammation and Colon Cancer. Frontiers in Physiology, 12, Article ID: 662739. [Google Scholar] [CrossRef] [PubMed]
[44] Wang, X., Wang, J., Rao, B. and Deng, L. (2017) Gut Flora Profiling and Fecal Metabolite Composition of Colorectal Cancer Patients and Healthy Individuals. Experimental & Therapeutic Medicine, 12, 2848-2854. [Google Scholar] [CrossRef] [PubMed]
[45] O’Keefe, S.J.D. (2016) Diet, Microorganisms and Their Metabolites, and Colon Cancer. Nature Reviews. Gastroenterology & Hepatology, 13, 691-706. [Google Scholar] [CrossRef] [PubMed]
[46] Han, A., Bennett, N., Ahmed, B., Whelan, J. and Donohoe, D.R. (2018) Butyrate Decreases Its Own Oxidation in Colorectal Cancer Cells through Inhibition of Histone Deacetylases. Oncotarget, 9, 27280-27292. [Google Scholar] [CrossRef] [PubMed]
[47] Borthakur, A., Priyamvada, S., Kumar, A., Natarajan, A.A., Gill, R.K., Alrefai, W.A., et al. (2012) A Novel Nutrient Sensing Mechanism Underlies Substrate-Induced Regulation of Monocarboxylate Transporter-1. American Journal of Physiology-Gastrointestinal and Liver Physiology, 303, G1126-G1133. [Google Scholar] [CrossRef] [PubMed]
[48] Tang, Y., Chen, Y., Jiang, H., Robbins, G.T. and Nie, D. (2011) G-Protein-Coupled Receptor for Short-Chain Fatty Acids Suppresses Colon Cancer. International Journal of Cancer, 128, 847-856. [Google Scholar] [CrossRef] [PubMed]
[49] Martin-Gallausiaux, C., Marinelli, L., Blottière, H.M., Larraufie, P. and Lapaque, N. (2020) SCFA: Mechanisms and Functional Importance in the Gut. Proceedings of the Nutrition Society, 80, 37-49. [Google Scholar] [CrossRef
[50] Soret, R., Chevalier, J., De Coppet, P., Poupeau, G., Derkinderen, P., Segain, J.P., et al. (2010) Short-Chain Fatty Acids Regulate the Enteric Neurons and Control Gastrointestinal Motility in Rats. Gastroenterology, 138, 1772-1782.e4. [Google Scholar] [CrossRef] [PubMed]
[51] Hurst, N.R., Kendig, D.M., Murthy, K.S. and Grider, J.R. (2014) The Short Chain Fatty Acids, Butyrate and Propionate, Have Differential Effects on the Motility of the Guinea Pig Colon. Neurogastroenterology & Motility, 26, 1586-1596. [Google Scholar] [CrossRef] [PubMed]
[52] Grider, J.R. and Piland, B.E. (2007) The Peristaltic Reflex Induced by Short-Chain Fatty Acids Is Mediated by Sequential Release of 5-HT and neuronal CGRP but not BDNF. American Journal of Physiology Gastrointestinal & Liver Physiology, 292, G429- G437. [Google Scholar] [CrossRef] [PubMed]