1.上海中医药大学中药研究所,上海市复方中药重点实验室,中药标准化教育部重点实验室暨国家中医药管理局中药新资源与质量评价重点实验室(上海 201203)
2.上海中药标准化研究中心(上海 201203)
王紫轩,男,硕士研究生,主要从事中药防治代谢性疾病生物学机制研究工作
丁丽丽,研究员,博士研究生导师; E-mail: nail8219@hotmail.com
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王紫轩,薛琼雯,罗亦轩,等.中药通过肠道菌群改善肥胖症及其相关代谢性疾病的作用机制研究进展[J].上海中医药杂志,2023,57(2):1-7.
WANG Zixuan,XUE Qiongwen,LUO Yixuan,et al.Research progress on mechanisms of traditional Chinese medicine in improving obesity and its related metabolic diseases through gut microbiota[J].Shanghai Journal of Traditional Chinese Medicine,2023,57(2):1-7.
王紫轩,薛琼雯,罗亦轩,等.中药通过肠道菌群改善肥胖症及其相关代谢性疾病的作用机制研究进展[J].上海中医药杂志,2023,57(2):1-7. DOI: 10.16305/j.1007-1334.2023.2211080.
WANG Zixuan,XUE Qiongwen,LUO Yixuan,et al.Research progress on mechanisms of traditional Chinese medicine in improving obesity and its related metabolic diseases through gut microbiota[J].Shanghai Journal of Traditional Chinese Medicine,2023,57(2):1-7. DOI: 10.16305/j.1007-1334.2023.2211080.
肥胖症及其相关代谢性疾病的发病率逐年增长,引发了全球性的公共健康问题。越来越多的研究发现肥胖症的发生发展与肠道菌群的结构及功能变化密切相关,两者关系的失衡被认为是代谢障碍的标志之一。中医药在治疗多种糖脂代谢紊乱引起的代谢性疾病中积累了丰富的经验,其在减重、改善糖脂代谢方面效果显著。但中药及其复方的有效成分口服生物利用度低,很难在靶器官达到起效浓度,而肠道可能是其主要作用器官。围绕肥胖症及其相关代谢性疾病与肠道菌群的相互作用,综述中药通过调节肠道菌群改善肥胖症、Ⅱ型糖尿病、代谢相关脂肪性肝病等代谢性疾病的研究进展,旨在为中药防治肥胖症等代谢性疾病提供理论依据,并为靶向肠道菌群抗肥胖及其并发症的药物研发提供参考策略。
The incidence of obesity and its related metabolic diseases is increasing year by year, causing a global public health problem. More and more studies have found that the occurrence and development of obesity are closely related to the structural and functional changes of gut microbiota, and the imbalance of the relationship between the two is considered one of the hallmarks of metabolic disorders. Traditional Chinese medicine in our country has accumulated rich experience in the treatment of many chronic diseases, including diseases caused by disorders of glucose and lipid metabolism, and it has shown significant effects on weight loss and improvement of glucose and lipid metabolism. However, the oral bioavailability of the active ingredients of traditional Chinese medicines and formulas is low, and it is difficult to reach the effective concentration in target organs while the intestine may be the main organ of action. Focusing on the interaction between obesity and its related metabolic diseases and gut microbiota, we summarized the current research progress of traditional Chinese medicine in improving metabolic diseases such as obesity, type Ⅱ diabetes, and metabolic associated fatty liver disease by regulating gut microbiota in this review, aiming to provide a theoretical basis for the traditional Chinese medicine prevention and treatment of obesity and other metabolic diseases, and provide a reference strategy for the development of drugs targeting gut microbiota against obesity and its complications.
肥胖代谢性疾病中药肠道菌群糖脂代谢Ⅱ型糖尿病代谢相关脂肪性肝病
obesitymetabolic diseasetraditional Chinese herbal medicinegut microbiotaglucolipid metabolismtype Ⅱ diabetesmetabolism associated fatty liver disease
PICHE M E, TCHERNOF A, DESPRES J P. Obesity phenotypes, diabetes, and cardiovascular diseases[J]. Circ Res, 2020, 126(11): 1477-1500.
ADEVA-ANDANY M M, RANAL-MUINO E, VILA-ALTESOR M, et al. Dietary habits contribute to define the risk of type 2 diabetes in humans[J]. Clin Nutr ESPEN, 2019, 34: 8-17.
WILBORN C, BECKHAM J, CAMPBELL B, et al. Obesity: prevalence, theories, medical consequences, management, and research directions[J]. J Int Soc Sports Nutr, 2005, 2(2): 4-31.
World Health Organization. World Obesity Day 2022—Accelerating action to stop obesity[EB/OL].[2022-10-18].https://www.who.int/news/item/04-03-2022-world-obesity-day-2022-accelerating-action-to-stop-obesityhttps://www.who.int/news/item/04-03-2022-world-obesity-day-2022-accelerating-action-to-stop-obesity.
CLARKE G, STILLING R M, KENNEDY P J, et al. Minireview: Gut microbiota: the neglected endocrine organ[J]. Mol Endocrinol, 2014, 28(8): 1221-1238.
VILLANUEVA-MILLAN M J, PEREZ-MATUTE P, OTEO J A. Gut microbiota: a key player in health and disease. A review focused on obesity[J]. J Physiol Biochem, 2015, 71(3): 509-525.
LIU R, HONG J, XU X, et al. Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention[J]. Nat Med, 2017, 23(7): 859-868.
KARLSSON F H, 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.
WAMPACH L, HEINTZ-BUSCHART A, HOGAN A, et al. Colonization and succession within the human gut microbiome by archaea, bacteria, and microeukaryotes during the first year of life[J]. Front Microbiol, 2017, 8: 738.
TURNBAUGH P J, LEY R E, MAHOWALD M A, et al. An obesity-associated gut microbiome with increased capacity for energy harvest[J]. Nature, 2006, 444(7122): 1027-1031.
BAJZER M, SEELEY R J. Physiology: obesity and gut flora[J]. Nature, 2006, 444(7122): 1009-1010.
KOBYLIAK N, CONTE C, CAMMAROTA G, et al. Probiotics in prevention and treatment of obesity: a critical view[J]. Nutr Metab (Lond), 2016, 13: 14.
HILL C, GUARNER F, REID G, et al. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic[J]. Nat Rev Gastroenterol Hepatol, 2014, 11(8): 506-514.
CANI P D, BIBILONI R, KNAUF C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice[J]. Diabetes, 2008, 57(6): 1470-1481.
GRANT R W, DIXIT V D. Mechanisms of disease: inflammasome activation and the development of type 2 diabetes[J]. Front Immunol, 2013, 4: 50.
BALAKUMAR M, PRABHU D, SATHISHKUMAR C, et al. Improvement in glucose tolerance and insulin sensitivity by probiotic strains of Indian gut origin in high-fat diet-fed C57BL/6J mice[J]. Eur J Nutr, 2018, 57(1): 279-295.
NAGATA N, XU L, KOHNO S, et al. Glucoraphanin ameliorates obesity and insulin resistance through adipose tissue browning and reduction of metabolic endotoxemia in mice[J]. Diabetes, 2017, 66(5): 1222-1236.
ARMANI R G, RAMEZANI A, YASIR A, et al. Gut microbiome in chronic kidney disease[J]. Curr Hypertens Rep, 2017, 19(4): 29.
TOLHURST G, HEFFRON H, LAM Y S, et al. Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2[J]. Diabetes, 2012, 61(2): 364-371.
SANSOME D J, XIE C, VEEDFALD S, et al. Mechanism of glucose-lowering by metformin in type 2 diabetes: Role of bile acids[J]. Diabetes Obes Metab, 2020, 22(2): 141-148.
LONG S L, GAHAN C G M, JOYCE S A. Interactions between gut bacteria and bile in health and disease[J]. Mol Aspects Med, 2017, 56: 54-65.
FIORUCCI S, DISTRUTTI E. Bile acid-activated receptors, intestinal microbiota, and the treatment of metabolic disorders[J]. Trends Mol Med, 2015, 21(11): 702-714.
MARTIN A, DEVKOTA S. Hold the door: role of the gut barrier in diabetes[J]. Cell Metab, 2018, 27(5): 949-951.
KOH A, DE VADDER F, KOVATCHEVA-DATCHARY P, et al. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites[J]. Cell, 2016, 165(6): 1332-1345.
SANNA S, VAN ZUYDAM N R, MAHAJAN A, et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases[J]. Nat Genet, 2019, 51(4): 600-605.
BUHMANN H, LE ROUX C W, BUETER M. The gut-brain axis in obesity[J]. Best Pract Res Clin Gastroenterol, 2014, 28(4): 559-571.
WAHLSTROM A, SAYIN S I, MARSCHALL H U, et al. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism[J]. Cell Metab, 2016, 24(1): 41-50.
MALLMANN N H, LIMA E S, LALWANI P. Dysregulation of tryptophan catabolism in metabolic syndrome[J]. Metab Syndr Relat Disord, 2018, 16(3): 135-142.
HE J, ZHANG P, SHEN L, et al. Short-chain fatty acids and their association with signalling pathways in inflammation, glucose and lipid metabolism[J]. Int J Mol Sci, 2020, 21(17): 6356.
LI Z, YI C X, KATIRAEI S, et al. Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit[J]. Gut, 2018, 67(7): 1269-1279.
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.
FENG R, SHOU J W, ZHAO Z X, et al. Transforming berberine into its intestine-absorbable form by the gut microbiota[J]. Sci Rep, 2015, 5: 12155.
KONG W, WEI J, ABIDI P, et al. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins[J]. Nat Med, 2004, 10(12): 1344-1351.
ZHANG Z, ZHANG H, LI B, et al. Berberine activates thermogenesis in white and brown adipose tissue[J]. Nat Commun, 2014, 5: 5493.
WANG K, FENG X, CHAI L, et al. The metabolism of berberine and its contribution to the pharmacological effects[J]. Drug Metab Rev, 2017, 49(2): 139-157.
LI M, SHU X, XU H, et al. Integrative analysis of metabolome and gut microbiota in diet-induced hyperlipidemic rats treated with berberine compounds[J]. J Transl Med, 2016, 14(1): 237.
ZHANG Y, GU Y, REN H, et al. Gut microbiome-related effects of berberine and probiotics on type 2 diabetes (the PREMOTE study)[J]. Nat Commun, 2020, 11(1): 5015.
XU X, YI H, WU J, et al. Therapeutic effect of berberine on metabolic diseases: Both pharmacological data and clinical evidence[J]. Biomed Pharmacother, 2021, 133: 110984.
ZHU L, ZHANG D, ZHU H, et al. Berberine treatment increases Akkermansia in the gut and improves high-fat diet-induced atherosclerosis in Apoe(-/-) mice[J]. Atherosclerosis, 2018, 268: 117-126.
LIU Y L, ZHANG Q Z, WANG Y R, et al. Astragaloside Ⅳ improves high-fat diet-induced hepatic steatosis in nonalcoholic fatty liver disease rats by regulating inflammatory factors level via TLR4/NF-kappaB signaling pathway[J]. Front Pharmacol, 2020, 11: 605064.
HONG Y, SHENG L, ZHONG J, et al. Desulfovibrio vulgaris, a potent acetic acid-producing bacterium, attenuates nonalcoholic fatty liver disease in mice[J]. Gut Microbes, 2021, 13(1): 1-20.
WANG X, SHI L, WANG X, et al. MDG-1, an Ophiopogon polysaccharide, restrains process of non-alcoholic fatty liver disease via modulating the gut-liver axis[J]. Int J Biol Macromol, 2019, 141: 1013-1021.
CHEN M, LIAO Z, LU B, et al. Huang-Lian-Jie-Du-Decoction ameliorates hyperglycemia and insulin resistant in association with gut microbiota modulation[J]. Front Microbiol, 2018, 9: 2380.
QUAN L H, ZHANG C, DONG M, et al. Myristoleic acid produced by enterococci reduces obesity through brown adipose tissue activation[J]. Gut, 2020, 69(7): 1239-1247.
CAI J, SUN L, GONZALEZ F J. Gut microbiota-derived bile acids in intestinal immunity, inflammation, and tumorigenesis[J]. Cell Host Microbe, 2022, 30(3): 289-300.
SELWYN F P, CSANAKY I L, ZHANG Y, et al. Importance of large intestine in regulating bile acids and glucagon-like peptide-1 in germ-free mice[J]. Drug Metab Dispos, 2015, 43(10): 1544-1556.
QADER M, XU J, YANG Y, et al. Chemistry behind the immunomodulatory activity of astragalus membranaceus[J]. Chin Med Cult, 2021, 4(4): 201-210.
ZHAI Y, ZHOU W, YAN X, et al. Astragaloside Ⅳ ameliorates diet-induced hepatic steatosis in obese mice by inhibiting intestinal FXR via intestinal flora remodeling[J]. Phytomedicine, 2022, 107: 154444.
ZHANG L, SHAO W F, YUAN L F, et al. Decreasing pro-inflammatory cytokine and reversing the immunosenescence with extracts of Pu-erh tea in senescence accelerated mouse (SAM)[J]. Food Chem, 2012, 135(4): 2222-2228.
HUANG F, ZHENG X, MA X, et al. Theabrownin from Pu-erh tea attenuates hypercholesterolemia via modulation of gut microbiota and bile acid metabolism[J]. Nat Commun, 2019, 10(1): 4971.
PEDERSEN H K, GUDMUNDSDOTTIR V, NIELSEN H B, et al. Human gut microbes impact host serum metabolome and insulin sensitivity[J]. Nature, 2016, 535(7612): 376-381.
HASLAM D W, JAMES W P. Obesity[J]. Lancet, 2005, 366(9492): 1197-1209.
ZENG S L, LI S Z, XIAO P T, et al. Citrus polymethoxyflavones attenuate metabolic syndrome by regulating gut microbiome and amino acid metabolism[J]. Sci Adv, 2020, 6(1): eaax6208.
MIN X H, YU T, QING Q, et al. Abnormal differentiation of intestinal epithelium and intestinal barrier dysfunction in diabetic mice associated with depressed Notch/NICD transduction in Notch/Hes1 signal pathway[J]. Cell Biol Int, 2014, 38(10): 1194-1204.
GOMEZ-ZORITA S, AGUIRRE L, MILTON-LASKIBAR I, et al. Relationship between changes in microbiota and liver steatosis induced by high-fat feeding-a review of rodent models[J]. Nutrients, 2019, 11(9):2156.
YU S, JIANG J, LI Q, et al. Schisantherin A alleviates non-alcoholic fatty liver disease by restoring intestinal barrier function[J]. Front Cell Infect Microbiol, 2022, 12: 855008.
马钰捷,余生兰,李琴琴,等. 五味子乙素通过增强肠道黏膜屏障功能改善小鼠非酒精性脂肪性肝病的研究[J]. 药学学报,2021, 56(10): 802-2808.
CHANG C J, LIN C S, LU C C, et al. Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota[J]. Nat Commun, 2015, 6: 7489.
AGIRMAN G, YU K B, HSIAO E Y. Signaling inflammation across the gut-brain axis[J]. Science, 2021, 374(6571): 1087-1092.
YOON H S, CHO C H, YUN M S, et al. Akkermansia muciniphila secretes a glucagon-like peptide-1-inducing protein that improves glucose homeostasis and ameliorates metabolic disease in mice[J]. Nat Microbiol, 2021, 6(5): 563-573.
SUN H, WANG N, CANG Z, et al. Modulation of microbiota-gut-brain axis by berberine resulting in improved metabolic status in high-fat diet-fed rats[J]. Obes Facts, 2016, 9(6): 365-378.
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