肠道微生物和肠—脑轴在肥胖发展中的作用
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摘要
肥胖和相关代谢综合征已成为全球最突出的健康问题之一,肠道微生物已被证明参与肥胖的发展,并可能对肥胖的发展和其干预治疗等提供重要的见解。最近的研究表明,肠道微生物和大脑的相互作用可能是肥胖的后果或解释因素,肠-脑轴是它们相互作用的联络枢纽。此外,肠道微生物可以通过肠道激素(包括ghrelin)以及迷走神经连接(影响能量消耗和CNS中与饮食行为相关的区域)来影响肠-脑轴,从而改变宿主行为。同时,肠道微生物代谢物和其产物还可以充当信号分子并调节肠内分泌细胞的激素分泌,如GLP1和PYY,从而调节食欲、肠道运动、能量吸收和储存以及能量消耗等摄食相关行为,进而影响肥胖的发展。所以,理解这些信号和激素作用并从药理学方法增强它们,可能为治疗肥胖提供一种重要的途径。
Obesity and related metabolic syndrome have become one of the most prominent health concerns in developed countries worldwide. Gut microbiota have been shown to be involved in the development of obesity and may provide important insights into the development of obesity and its intervention and treatment. Recent studies have shown that the interaction between intestinal microbes and the brain may be the consequence or explanation of obesity,and that the gut-brain axis is the focal point for their interaction. In addition,intestinal microorganisms can influence the gut-brain axis through gut hormones( including ghrelin) and vagal nerve connections( which affect energy consumption and dietary behavior-related areas of CNS),thereby changing host behavior. At the same time,microbial products and microbially produced metabolites can act as signaling molecules and regulate the secretion of hormones from intestinal enteroendocrine cells,such as GLP1 and PYY,which regulate appetite,intestinal motility,energy absorption and storage,and energy consumption,and other feedingrelated behaviors,and thereby influencing the development of obesity. Therefore,it is possible to provide an important route for the treatment of obesity by understanding the effects of these signals and hormonal and enhancing them from pharmacological methods.
Obesity and related metabolic syndrome have become one of the most prominent health concerns in developed countries worldwide. Gut microbiota have been shown to be involved in the development of obesity and may provide important insights into the development of obesity and its intervention and treatment. Recent studies have shown that the interaction between intestinal microbes and the brain may be the consequence or explanation of obesity,and that the gut-brain axis is the focal point for their interaction. In addition,intestinal microorganisms can influence the gut-brain axis through gut hormones( including ghrelin) and vagal nerve connections( which affect energy consumption and dietary behavior-related areas of CNS),thereby changing host behavior. At the same time,microbial products and microbially produced metabolites can act as signaling molecules and regulate the secretion of hormones from intestinal enteroendocrine cells,such as GLP1 and PYY,which regulate appetite,intestinal motility,energy absorption and storage,and energy consumption,and other feedingrelated behaviors,and thereby influencing the development of obesity. Therefore,it is possible to provide an important route for the treatment of obesity by understanding the effects of these signals and hormonal and enhancing them from pharmacological methods.
引文
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[43] Bauer PV, Hamr SC, Duca FA. Regulation of energy balance by a gut-brain axis and involvement of the gut microbiota[J].Cell Mol Life Sci,2016,73(4):737-755.
[44] De Vadder F, et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits[J].Cell,2014,156(1-2):84-96.
[45] Neyrinck AM,et al. Wheat-derived arabinoxylan oligosaccharides with prebiotic effect increase satietogenic gut peptides and reduce metabolic endotoxemia in diet-induced obese mice[J].Nutr Diabetes,2012,2:e28.
[46] Grima M, Dixon JB. Obesity recommendations for management in general practice and beyond[J]. Aust Fam Physician,2013,42(8):532-541.
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[2] Niccolai E,Boem F,Russo E,et al. The gut-brain axis in the neuropsychological disease model of obesity:a classical movie revised by the emerging director “microbiome”[J].Nutrients,2019,11(1):E156.
[3]李昱,杜余辉,周帅,等.肠道微生物群在2型糖尿病病理生理学中的作用[J].中华糖尿病杂志,2019,11(3):218-221.
[4] Bliss ES,Whiteside E. The gut-brain axis,the human gut microbiota and their integration in the development of obesity[J].Front Physiol,2018,9:900.
[5] Backhed F,Ding H,Wang T,et al. The gut microbiota as an environmental factor that regulates fat storage[J]. Proc Natl Acad Sci U S A,2004,101(44):15718-15723.
[6] Turnbaugh PJ,Ley RE,Mahowald MA,et al. An obesityassociated gut microbiome with increased capacity for energy harvest[J].Nature,2006,444(7122):1027-1031.
[7] Ochoa-Reparaz J,et al. The second brain:is the gut microbiota a link between obesity and central nervous system disorders?[J].Current Obesity Reports,2016,5(1):51-64.
[8] Martin CR,Mayer EA. Gut-brain axis and behavior[J].Nestle Nutr Inst workshop Ser,2017,88:45-53.
[9] Mayer EA,Tillisch K,Gupta A. Gut/brain axis and the microbiota[J].J Clin Invest,2015,125(3):926-938.
[10] Cryan J F,Dinan TG. Mind-altering microorganisms:the impact of the gut microbiota on brain and behaviour[J].Nat Rev Neurosci,2012,13(10):701-712.
[11] Mayer EA. Gut feelings:the emerging biology of gut-brain communication[J]. Nat Rev Neurosci, 2011,12(8):453-466.
[12]林璋,祖先鹏,谢海胜,等.肠道菌群与人体疾病发病机制的研究进展[J].药学学报,2016(6):843-852.
[13] De Vos WM,De Vos EAJ. Role of the intestinal microbiome in health and disease:from correlation to causation[J].Nutr Rev,2012,70:S45-S56.
[14] Wang HX,Wang YP. Gut Microbiota-brain axis[J].Chin Med J(Engl),2016,129(19):2373-2380.
[15]严人,江慧勇,李兰娟.人体微生态与健康和疾病[J].微生物学报,2017,57(6):793-805.
[16] Moreno-Indias I,Cardona F,Tinahones FJ,et al. Impact of the gut microbiota on the development of obesity and type2 diabetes mellitus[J].Front Microbiol,2014,5:190.
[17] Khan I,Yasir M,Azhar EI,et al. Implication of gut microbiota in human health[J].Cns Neurol Disord-Dr,2014,13(8):1325-1333.
[18] Rosenbaum M,Knight R,Leibel RL. The gut microbiota in human energy homeostasis and obesity[J]. Trends Endocrinol Metab,2015,26(9):493-501.
[19] Musso G,Gambino R,Cassader M. Obesity,diabetes,and gut microbiota:the hygiene hypothesis expanded?[J].Diabetes Care,2010,33(10):2277-2284.
[20] Van De Wouw M,Schellekens H,Dinan TG,et al. Microbiota-gut-brain axis:modulator of host metabolism and appetite[J].J Nutr,2017,147(5):727-745.
[21] Turnbaugh PJ,et al. A core gut microbiome in obese and lean twins[J].Nature,2009,457(7228):480-484.
[22] Turnbaugh PJ,Ley RE,Mahowald MA,et al. An obesityassociated gut microbiome with increased capacity for energy harvest[J].Nature,2006,444(7122):1027-1031.
[23] Gerard P. Gut microbiota and obesity[J].Cell Mol Life Sci,2016,73(1):147-162.
[24] Kong LC,Tap J,Aron-Wisnewsky J,et al. Gut microbiota after gastric bypass in human obesity:increased richness and associations of bacterial genera with adipose tissue genes[J].Am J Clin Nutr,2013,98(1):16-24.
[25] De Clercq NC,et al. Gut microbiota and the gut-brain axis:new insights in the pathophysiology of metabolic syndrome[J].Psychosom Med,2017,79(8):874-879.
[26] Liou AP,et al. Conserved shifts in the gut microbiota due to gastric bypass reduce host weight and adiposity[J]. Sci Transl Med,2013,5(178):178ra41.
[27] Zhang LS,Davies SS. Microbial metabolism of dietary components to bioactive metabolites:opportunities for new therapeutic interventions[J].Genome Med,2016,8(1):46.
[28] Torres-Fuentes C,et al. The microbiota-gut-brain axis in obesity[J].Lancet Gastroenterol,2017,2(10):747-756.
[29] Dao MC,Clement K. Gut microbiota and obesity:cncepts relevant to clinical care[J]. Eur J Intern Med,2018,48:18-24.
[30] Patterson E,et al. Gut microbiota,obesity and diabetes[J].Postgrad Med J,2016,92(1087):286-300.
[31] Menni C,et al. Gut microbiome diversity and high-fibre intake are related to lower long-term weight gain[J]. Int J Obes(Lond),2017,41(7):1099-1105.
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[37] Scriven M,Dinan TG,Cryan JF,et al. Neuropsychiatric disorders:influence of gut microbe to brain signalling[J].Diseases,2018,6(3):pii:E78.
[38] Mulders RJ,et al. Microbiota in obesity:interactions with enteroendocrine,immune and central nervous systems[J].Obes Rev,2018,19(4):435-451.
[39] Agusti A,Garcia-Pardo MP,Lopez-Almela I,et al. Interplay between the gut-brain axis,obesity and cognitive Function[J].Front Neurosci,2018,12:155.
[40] Kairupan TS,Amitani H,Cheng KC,et al. Role of gastrointestinal hormones in feeding behavior and obesity treatment[J].J Gastroenterol,2016,51(2):93-103.
[41] Buhmann H,Le Roux CW,Bueter M. The gut-brain axis in obesity[J].Best Pract Res Cl Ga,2014,28(4):559-571.
[42] Hussain SS,Bloom SR. The regulation of food intake by the gut-brain axis:implications for obesity[J]. Int J Obes,2013,37(5):625-633.
[43] Bauer PV, Hamr SC, Duca FA. Regulation of energy balance by a gut-brain axis and involvement of the gut microbiota[J].Cell Mol Life Sci,2016,73(4):737-755.
[44] De Vadder F, et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits[J].Cell,2014,156(1-2):84-96.
[45] Neyrinck AM,et al. Wheat-derived arabinoxylan oligosaccharides with prebiotic effect increase satietogenic gut peptides and reduce metabolic endotoxemia in diet-induced obese mice[J].Nutr Diabetes,2012,2:e28.
[46] Grima M, Dixon JB. Obesity recommendations for management in general practice and beyond[J]. Aust Fam Physician,2013,42(8):532-541.
[47] Mumphrey MB,et al. Roux-en-Y gastric bypass surgery increases number but not density of CCK-,GLP-1-,5-HT-,and neurotensin-expressing enteroendocrine cells in rats[J].Neurogastroenterol Motil,2013,25(1):e70-79.