肠道菌群和胆汁酸通路在非酒精性脂肪性肝病发病中的作用

孙梦园; 向晓星

doi:10.3969/j.issn.1001-5256.2020.12.040

肠道菌群和胆汁酸通路在非酒精性脂肪性肝病发病中的作用

DOI: 10.3969/j.issn.1001-5256.2020.12.040

1. 扬州大学医学院
2. 扬州大学临床医学院消化内科

详细信息

中图分类号: R575.5
计量
- 文章访问数: 732
- HTML全文浏览量: 59
- PDF下载量: 92
- 被引次数: 0
出版历程
- 收稿日期: 2020-04-21
- 出版日期: 2020-12-20

Role of gut microbiota and bile acid pathway in nonalcoholic fatty liver disease

Yangzhou University Medical College
Department of Gastroenterology,School of Clinical Medicine,Yangzhou University

摘要

摘要:
非酒精性脂肪性肝病是一组病理生理机制尚不明确的疾病,与代谢综合征密切相关。肠道菌群产生的细菌成分及代谢产物调节糖脂代谢、炎症反应及氧化应激。胆汁酸激活其受体后通过多种信号通路调节免疫功能及能量、物质代谢。肠道菌群与胆汁酸通过肠肝循环相互作用,二者结构及功能的改变参与非酒精性脂肪性肝病的发生发展。旨在综述肠道菌群、胆汁酸稳态失调及二者相互作用对非酒精性脂肪性肝病的影响。
- 非酒精性脂肪性肝病 /
- 胃肠道微生物组 /
- 胆酸类 /
- 病理过程
Abstract:
Nonalcoholic fatty liver disease is a group of diseases with unclear pathophysiological mechanism and is closely associated with metabolic syndrome. Bacterial components and metabolites produced by gut microbiota can regulate glucose and lipid metabolism,inflammatory response,and oxidative stress,and bile acids regulate immune function,energy metabolism,and material metabolism through various signaling pathways after activating their receptors. Gut microbiota and bile acids interact with each other through enterohepatic circulation,and the changes of their structure and function are involved in the development and progression of nonalcoholic fatty liver disease. This article reviews the effect of the homeostatic dysregulation of gut microbiota and bile acids and their interactions on nonalcoholic fatty liver disease.
- non-alcoholic fatty liver disease /
- gastrointestinal microbiome /
- cholic acids /
- pathologic processes

HTML全文

参考文献(38)

[1] European Association for the Study of the Liver(EASL),European Association for the Study of Diabetes(EASD),European Association for the Study of Obesity(EASO). EASL-EASDEASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease[J]. J Hepatol,2016,64(6):1388-1402.

[2] ESLAM M,SANYAL AJ,GEORGE J,et al. MAFLD:A consensus-driven proposed nomenclature for metabolic associated fatty liver disease[J]. Gastroenterology,2020,158(7):1999-2014. e1.

[3] BALLESTRI S,ZONA S,TARGHER G,et al. Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis[J]. J Gastroenterol Hepatol,2016,31(5):936-944.

[4] WIELAND A,FRANK DN,HARNKE B,et al. Systematic review:Microbial dysbiosis and nonalcoholic fatty liver disease[J]. Aliment Pharmacol Ther,2015,42(9):1051-1063.

[5] COPPLE BL,LI T. Pharmacology of bile acid receptors:Evolution of bile acids from simple detergents to complex signaling molecules[J]. Pharmacol Res,2016,104:9-21.

[6] ADAMS LA,WANG Z,LIDDLE C,et al. Bile acids associate with specific gut microbiota,low-level alcohol consumption and liver fibrosis in patients with non-alcoholic fatty liver disease[J]. Liver Int,2020,40(6):1356-1365.

[7] SAYIN SI,WAHLSTRM A,FELIN J,et al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid,a naturally occurring FXR antagonist[J]. Cell Metab,2013,17(2):225-235.

[8] OUT C,PATANKAR JV,DOKTOROVA M,et al. Gut microbiota inhibit Asbt-dependent intestinal bile acid reabsorption via Gata4[J]. J Hepatol,2015,63(3):697-704.

[9] JIA W,XIE G,JIA W. Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis[J]. Nat Rev Gastroenterol Hepatol,2018,15(2):111-128.

[10] 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.

[11] KURDI P,KAWANISHI K,MIZUTANI K,et al. Mechanism of growth inhibition by free bile acids in lactobacilli and bifidobacteria[J]. J Bacteriol,2006,188(5):1979-1986.

[12] WATANABE M,FUKIYA S,YOKOTA A. Comprehensive evaluation of the bactericidal activities of free bile acids in the large intestine of humans and rodents[J]. J Lipid Res,2017,58(6):1143-1152.

[13] MERRITT ME,DONALDSON JR. Effect of bile salts on the DNA and membrane integrity of enteric bacteria[J]. J Med Microbiol,2009,58(Pt 12):1533-1541.

[14] GADALETA RM,van ERPECUM KJ,OLDENBURG B,et al.Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease[J].Gut,2011,60(4):463-472.

[15] NATIVIDAD JM,LAMAS B,PHAM HP,et al. Bilophila wadsworthia aggravates high fat diet induced metabolic dysfunctions in mice[J]. Nat Commun,2018,9(1):2802.

[16] AMBALAM P,KONDEPUDI KK,NILSSON I,et al. Bile enhances cell surface hydrophobicity and biofilm formation of bifidobacteria[J]. Appl Biochem Biotechnol,2014,172(4):1970-1981.

[17] ZHENG X,HUANG F,ZHAO A,et al. Bile acid is a significant host factor shaping the gut microbiome of diet-induced obese mice[J]. BMC Biol,2017,15(1):120.

[18] de FARIA GHETTI F,OLIVEIRA DG,de OLIVEIRA JM,et al.Influence of gut microbiota on the development and progression of nonalcoholic steatohepatitis[J]. Eur J Nutr,2018,57(3):861-876.

[19] SHERRIFF JL,O’SULLIVAN TA,PROPERZI C,et al. Its potential role in nonalcoholic fatty liver disease,and the case for human and bacterial genes[J]. Adv Nutr,2016,7(1):5-13.

[20] SHEN F,ZHENG RD,SUN XQ,et al. Gut microbiota dysbiosis in patients with non-alcoholic fatty liver disease[J]. Hepatobiliary Pancreat Dis Int,2017,16(4):375-381.

[21] 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.

[22] CARBAJO-PESCADOR S,PORRAS D,GARCA-MEDIAVILLA MV,et al. Beneficial effects of exercise on gut microbiota functionality and barrier integrity,and gut-liver crosstalk in an in vivo model of early obesity and non-alcoholic fatty liver disease[J]. Dis Model Mech,2019,12(5):dmm039206.

[23] STANISLAWSKI MA,LOZUPONE CA,WAGNER BD,et al. Gut microbiota in adolescents and the association with fatty liver:The EPOCH study[J]. Pediatr Res,2018,84(2):219-227.

[24] SCHUMACHER JD,GUO GL. Pharmacologic modulation of bile acid-FXR-FGF15/FGF19 pathway for the treatment of nonalcoholic steatohepatitis[J]. Handb Exp Pharmacol,2019,256:325-357.

[25] MOUZAKI M,WANG AY,BANDSMA R,et al. Bile acids and dysbiosis in non-alcoholic fatty liver disease[J]. PLo S One,2016,11(5):e0151829.

[26] CAUSSY C,HSU C,SINGH S,et al. Serum bile acid patterns are associated with the presence of NAFLD in twins,and dose-dependent changes with increase in fibrosis stage in patients with biopsy-proven NAFLD[J]. Aliment Pharmacol Ther,2019,49(2):183-193.

[27] XI Y,LI H. Role of farnesoid X receptor in hepatic steatosis in nonalcoholic fatty liver disease[J]. Biomed Pharmacother,2020,121:109609.

[28] FANG Q,LI H,SONG Q,et al. Serum fibroblast growth factor19 levels are decreased in Chinese subjects with impaired fasting glucose and inversely associated with fasting plasma glucose levels[J]. Diabetes Care,2013,36(9):2810-2814.

[29] SHIHABUDEEN MS,ROY D,JAMES J,et al. Chenodeoxycholic acid,an endogenous FXR ligand alters adipokines and reverses insulin resistance[J]. Mol Cell Endocrinol,2015,414:19-28.

[30] JIAO N,BAKER SS,CHAPA-RODRIGUEZ A,et al. Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD[J]. Gut,2018,67(10):1881-1891.

[31] ADAMS LA,WANG Z,LIDDLE C,et al. Bile acids associate with specific gut microbiota,low-level alcohol consumption and liver fibrosis in patients with non-alcoholic fatty liver disease[J]. Liver Int,2020,40(6):1356-1365.

[32] PURI P,DAITA K,JOYCE A,et al. The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids[J]. Hepatology,2018,67(2):534-548.

[33] TAN X,LIU Y,LONG J,et al. Trimethylamine N-oxide aggravates liver steatosis through modulation of bile acid metabolism and inhibition of farnesoid X receptor signaling in nonalcoholic fatty liver disease[J]. Mol Nutr Food Res,2019,63(17):e1900257.

[34] CHEVRE R,TRIGUEROS-MOTOS L,CASTAO D,et al.Therapeutic modulation of the bile acid pool by Cyp8b1knockdown protects against nonalcoholic fatty liver disease in mice[J]. FASEB J,2018,32(7):3792-3802.

[35] JENA PK,SHENG L,NAGAR N,et al. Synbiotics bifidobacterium infantis and milk oligosaccharides are effective in reversing cancer-prone nonalcoholic steatohepatitis using western diet-fed FXR knockout mouse models[J]. J Nutr Biochem,2018,57:246-254.

[36] PATHAK P,XIE C,NICHOLS RG,et al. Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism[J].Hepatology,2018,68(4):1574-1588.

[37] NATIVIDAD JM,LAMAS B,PHAM HP,et al. Bilophila wadsworthia aggravates high fat diet induced metabolic dysfunctions in mice[J]. Nat Commun,2018,9(1):2802.

[38] MOURIES J,BRESCIA P,SILVESTRI A,et al. Microbiotadriven gut vascular barrier disruption is a prerequisite for nonalcoholic steatohepatitis development[J]. J Hepatol,2019,71(6):1216-1228.

施引文献

资源附件(0)

访问统计