肠道菌群与代谢性疾病关系研究进展

doi:10.3760/cma.j.issn.1007-1245.2023.16.002

摘要/Abstract

摘要：

代谢性疾病是一系列机体代谢异常疾病的总称，包括肥胖、糖尿病、非酒精性肝病等。人类肠道中有数以百亿的细菌，其产生的代谢产物可与人类宿主相互作用，从而影响着人类的健康。肠道微生物群与人类宿主的代谢健康密切相关，在异常情况下可能会导致各种常见的代谢疾病，如肥胖、2型糖尿病、非酒精性肝病、心肺代谢疾病、营养不良等。本文讨论了肠道菌群与常见的代谢性疾病的关系、致病机制，基于肠道菌群的代谢性疾病的治疗和预防方法，为代谢性疾病的治疗提供新方向。

关键词:

肠道菌群, 代谢性疾病, 肥胖, 2型糖尿病, 非酒精性肝病, 进展

Abstract:

Metabolic diseases refer to the general name for metabolic disorders, including obesity, diabetes, non-alcoholic liver disease, etc. There are tens of billions of bacteria in human gut; their metabolites can interact with the human hosts and affect human health. The gut microbiotas are closely related to the human hosts' metabolic health; in abnormal situations, they may lead to a variety of common metabolic diseases, such as obesity, type 2 diabetes, non-alcoholic liver disease, cardio-pulmonary metabolic diseases, malnutrition, etc. In this review, we discuss the relationship of gut microbiotas with common metabolic diseases, the pathogenic mechanisms leading to these diseases, and the treatment and prevention methods of metabolic diseases from the perspectives of gut microbiotas, so as to provide new directions for the treatment of metabolic diseases.

Key words:

Gut microbiotas, Metabolic diseases, Obesity, Type 2 diabetes, Non-alcoholic liver disease, Progress

方建锋.

肠道菌群与代谢性疾病关系研究进展 [J]. 国际医药卫生导报, 2023, 29(16): 2225-2229.

Fang Jianfeng.

Relationship between intestinal floras and metabolic diseases [J]. International Medicine and Health Guidance News, 2023, 29(16): 2225-2229.

参考文献

[1] Scheithauer TP, Dallinga-Thie GM, de Vos WM, et al. Causality of small and large intestinal microbiota in weight regulation and insulin resistance[J]. Mol Metab, 2016,5(9):759-770. DOI: 10.1016/j.molmet.2016.06.002.
[2] Lazar V, Ditu LM, Pircalabioru GG, et al. Aspects of gut microbiota and immune system interactions in infectious diseases, immunopathology, and cancer[J]. Front Immunol, 2018,9:1830. DOI: 10.3389/fimmu.2018.01830.
[3] Rowland I, Gibson G, Heinken A, et al. Gut microbiota functions: metabolism of nutrients and other food components[J]. Eur J Nutr, 2018,57(1):1-24. DOI: 10.1007/s00394-017-1445-8.
[4] Valdes AM, Walter J, Segal E, et al. Role of the gut microbiota in nutrition and health[J]. BMJ, 2018,361:k2179. DOI: 10.1136/bmj.k2179.
[5] Tomas J, Mulet C, Saffarian A, et al. High-fat diet modifies the PPAR-γ pathway leading to disruption of microbial and physiological ecosystem in murine small intestine[J]. Proc Natl Acad Sci U S A, 2016,113(40):E5934-E5943. DOI: 10.1073/pnas.1612559113.
[6] Thingholm LB, Rühlemann MC, Koch M, et al. Obese individuals with and without type 2 diabetes show different gut microbial functional capacity and composition[J]. Cell Host Microbe, 2019,26(2):252-264.e10. DOI: 10.1016/j.chom.2019.07.004.
[7] Bäckhed F, Manchester JK, Semenkovich CF, et al. Mechanisms underlying the resistance to diet-induced obesity in germ-free mice[J]. Proc Natl Acad Sci U S A, 2007,104(3):979-84. DOI: 10.1073/pnas.0605374104.
[8] Rabot S, Membrez M, Bruneau A, et al. Germ-free C57BL/6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism[J]. FASEB J, 2010,24(12):4948-4959. DOI: 10.1096/fj.10-164921.
[9] Fei N, Zhao L. An opportunistic pathogen isolated from the gut of an obese human causes obesity in germfree mice[J]. ISME J, 2013,7(4):880-884. DOI: 10.1038/ismej.2012.153.
[10] Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest[J]. Nature, 2006,444(7122):1027-1031. DOI: 10.1038/nature05414.
[11] Ridaura VK, Faith JJ, Rey FE, et al. Gut microbiota from twins discordant for obesity modulate metabolism in mice[J]. Science, 2013,341(6150):1241214. DOI: 10.1126/science.1241214.
[12] Saeedi P, Petersohn I, Salpea P, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: results from the International Diabetes Federation Diabetes Atlas, 9th edition[J]. Diabetes Res Clin Pract, 2019,157:107843. DOI: 10.1016/j.diabres.2019.107843.
[13] Morigny P, Houssier M, Mouisel E, et al. Adipocyte lipolysis and insulin resistance[J]. Biochimie, 2016,125:259-66. DOI: 10.1016/j.biochi.2015.10.024.
[14] Karlsson FH, Tremaroli V, Nookaew I, et al. Gut metagenome in European women with normal, impaired and diabetic glucose control[J]. Nature, 2013,498(7452):99-103. DOI: 10.1038/nature12198.
[15] Le Chatelier E, Nielsen T, Qin J, et al. Richness of human gut microbiome correlates with metabolic markers[J]. Nature, 2013,500(7464):541-546. DOI: 10.1038/nature12506.
[16] Qin J, Li Y, Cai Z, et al. A metagenome-wide association study of gut microbiota in type 2 diabetes[J]. Nature, 2012,490(7418):55-60. DOI: 10.1038/nature11450.
[17] Karlsson CL, Onnerfält J, Xu J, et al. The microbiota of the gut in preschool children with normal and excessive body weight[J]. Obesity (Silver Spring), 2012,20(11):2257-2261. DOI: 10.1038/oby.2012.110.
[18] Yuan J, Chen C, Cui J, et al. Fatty liver disease caused by high-alcohol-producing klebsiella pneumoniae[J]. Cell Metab, 2019,30(4):675-688.e7. DOI: 10.1016/j.cmet.2019.08.018.
[19] Zhu L, Baker SS, Gill C, et al. Characterization of gut microbiomes in nonalcoholic steatohepatitis (NASH) patients: a connection between endogenous alcohol and NASH[J]. Hepatology, 2013,57(2):601-609. DOI: 10.1002/hep.26093.
[20] Gomes JMG, Costa JA, Alfenas RCG. Metabolic endotoxemia and diabetes mellitus: a systematic review[J]. Metabolism, 2017,68:133-144. DOI: 10.1016/j.metabol.2016.12.009.
[21] Matheus VA, Monteiro L, Oliveira RB, et al. Butyrate reduces high-fat diet-induced metabolic alterations, hepatic steatosis and pancreatic beta cell and intestinal barrier dysfunctions in prediabetic mice[J]. Exp Biol Med (Maywood), 2017,242(12):1214-1226. DOI: 10.1177/1535370217708188.
[22] Song MJ, Kim KH, Yoon JM, et al. Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes[J]. Biochem Biophys Res Commun, 2006,346(3):739-745. DOI: 10.1016/j.bbrc.2006.05.170.
[23] Zozulinska D, Wierusz-Wysocka B.Type 2 diabetes mellitus as inflammatory disease[J].Diabetes Research and Clinical Practice,2006,74(2):S12-S16.DOI:10.1016/j.diabres.2006.06.007.
[24] Roohi A, Tabrizi M, Abbasi F, et al. Serum IL-17, IL-23, and TGF-β levels in type 1 and type 2 diabetic patients and age-matched healthy controls[J]. Biomed Res Int, 2014,2014:718946. DOI: 10.1155/2014/718946.
[25] Abdel-Moneim A, Bakery HH, Allam G. The potential pathogenic role of IL-17/Th17 cells in both type 1 and type 2 diabetes mellitus[J]. Biomed Pharmacother, 2018,101:287-292. DOI: 10.1016/j.biopha.2018.02.103.
[26] von Scholten BJ, Reinhard H, Hansen TW, et al. Markers of inflammation and endothelial dysfunction are associated with incident cardiovascular disease, all-cause mortality, and progression of coronary calcification in type 2 diabetic patients with microalbuminuria[J]. J Diabetes Complications, 2016,30(2):248-255. DOI: 10.1016/j.jdiacomp.2015.11.005.
[27] Roy CC, Kien CL, Bouthillier L, et al. Short-chain fatty acids: ready for prime time?[J]. Nutr Clin Pract, 2006,21(4):351-366. DOI: 10.1177/0115426506021004351.
[28] Macfarlane S, Macfarlane GT. Regulation of short-chain fatty acid production[J]. Proc Nutr Soc, 2003,62(1):67-72. DOI: 10.1079/PNS2002207.
[29] Zeng H, Chi H. Metabolic control of regulatory T cell development and function[J]. Trends Immunol, 2015,36(1):3-12. DOI: 10.1016/j.it.2014.08.003.
[30] Lin HV, Frassetto A, Kowalik EJ, et al. Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms[J]. PLoS One, 2012,7(4):e35240. DOI: 10.1371/journal.pone.0035240.
[31] Gao Z, Yin J, Zhang J, et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice[J]. Diabetes, 2009,58(7):1509-1517. DOI: 10.2337/db08-1637.
[32] Cani PD. Gut cell metabolism shapes the microbiome[J]. Science, 2017,357(6351):548-549. DOI: 10.1126/science.aao2202.
[33] Cani PD. Human gut microbiome: hopes, threats and promises[J]. Gut, 2018,67(9):1716-1725. DOI: 10.1136/gutjnl-2018-316723.
[34] Vítek L, Haluzík M. The role of bile acids in metabolic regulation[J]. J Endocrinol, 2016,228(3):R85-96. DOI: 10.1530/JOE-15-0469.
[35] Bennion LJ, Grundy SM. Effects of diabetes mellitus on cholesterol metabolism in man[J]. N Engl J Med, 1977,296(24):1365-1371. DOI: 10.1056/NEJM197706162962401.
[36] Abrams JJ, Ginsberg H, Grundy SM. Metabolism of cholesterol and plasma triglycerides in nonketotic diabetes mellitus[J]. Diabetes, 1982,31(10):903-910. DOI: 10.2337/diab.31.10.903.
[37] 梁贝贝,凌宏威,周冬梅,等.血清总胆汁酸水平与2型糖尿病的关系[J].现代医学,2019,47(3):250-254.DOI:10.3969/j.issn.1671-7562.2019.03.002.
[38] Mantovani A, Dalbeni A, Peserico D, et al. Plasma bile acid profile in patients with and without type 2 diabetes[J]. Metabolites, 2021,11(7):453. DOI: 10.3390/metabo11070453.
[39] Herrema H, Meissner M, van Dijk TH, et al. Bile salt sequestration induces hepatic de novo lipogenesis through farnesoid X receptor- and liver X receptor alpha-controlled metabolic pathways in mice[J]. Hepatology, 2010,51(3):806-816. DOI: 10.1002/hep.23408.
[40] Park S, Bae JH. Probiotics for weight loss: a systematic review and meta-analysis[J]. Nutr Res, 2015,35(7):566-575. DOI: 10.1016/j.nutres.2015.05.008.
[41] Mátis G, Kulcsár A, Turowski V, et al. Effects of oral butyrate application on insulin signaling in various tissues of chickens[J]. Domest Anim Endocrinol, 2015,50:26-31. DOI: 10.1016/j.domaniend.2014.07.004.
[42] Ejtahed HS, Mohtadi-Nia J, Homayouni-Rad A, et al. Effect of probiotic yogurt containing Lactobacillus acidophilus and Bifidobacterium lactis on lipid profile in individuals with type 2 diabetes mellitus[J]. J Dairy Sci, 2011,94(7):3288-3294. DOI: 10.3168/jds.2010-4128.
[43] Naito E, Yoshida Y, Makino K, et al. Beneficial effect of oral administration of Lactobacillus casei strain Shirota on insulin resistance in diet-induced obesity mice[J]. J Appl Microbiol, 2011,110(3):650-657. DOI: 10.1111/j.1365-2672.2010.04922.x.
[44] Roller M, Rechkemmer G, Watzl B. Prebiotic inulin enriched with oligofructose in combination with the probiotics Lactobacillus rhamnosus and Bifidobacterium lactis modulates intestinal immune functions in rats[J]. J Nutr, 2004,134(1):153-156. DOI: 10.1093/jn/134.1.153.
[45] Rinott E, Youngster I, Yaskolka Meir A, et al. Effects of diet-modulated autologous fecal microbiota transplantation on weight regain[J]. Gastroenterology, 2021,160(1):158-173.e10. DOI: 10.1053/j.gastro.2020.08.041.
[46] Alang N, Kelly CR. Weight gain after fecal microbiota transplantation[J]. Open Forum Infect Dis, 2015,2(1):ofv004. DOI: 10.1093/ofid/ofv004.
[47] Kootte RS, Levin E, Salojärvi J, et al. Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition[J]. Cell Metab, 2017,26(4):611-619.e6. DOI: 10.1016/j.cmet.2017.09.008.
[48] Vrieze A, Van Nood E, Holleman F, et al. Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome[J]. Gastroenterology, 2012,143(4):913-6.e7. DOI: 10.1053/j.gastro.2012.06.031.
[49] Witjes JJ, Smits LP, Pekmez CT, et al. Donor fecal microbiota transplantation alters gut microbiota and metabolites in obese individuals with steatohepatitis[J]. Hepatol Commun, 2020,4(11):1578-1590. DOI: 10.1002/hep4.1601.
[50] Hou YY, Ojo O, Wang LL, et al. A Randomized controlled trial to compare the effect of peanuts and almonds on the cardio-metabolic and inflammatory parameters in patients with type 2 diabetes mellitus[J]. Nutrients, 2018,10(11):1565. DOI: 10.3390/nu10111565.
[51] Fernández-Cao JC, Warthon-Medina M, H Moran V, et al. Zinc intake and status and risk of type 2 diabetes mellitus: a systematic review and meta-analysis[J]. Nutrients, 2019,11(5):1027. DOI: 10.3390/nu11051027.
[52] Song S, Lee JE. Dietary patterns related to triglyceride and high-density lipoprotein cholesterol and the incidence of type 2 diabetes in Korean men and women[J]. Nutrients, 2018,11(1):8. DOI: 10.3390/nu11010008.