Non-alcoholic fatty liver disease (NAFLD)is one of the most common metabolic diseases currently in the context of obesity worldwide,which contains a spectrum of chronic liver diseases,including hepatic steatosis, non-...Non-alcoholic fatty liver disease (NAFLD)is one of the most common metabolic diseases currently in the context of obesity worldwide,which contains a spectrum of chronic liver diseases,including hepatic steatosis, non-alcoholic steatohepatitis and hepatic carcinoma.In addition to the classical "Two-hit"theory,NAFLD has been recognized as a typical gut microbiota-related disease because of the intricate role of gut microbiota in maintaining human health and disease formation.Moreover,gut microbiota is even regarded as a "metabolic organ"that play complementary roles to that of liver in many aspects.The mechanisms underlying gut microbiota-mediated development of NAFLD include modulation of host energy metabolism,insulin sensitivity, and bile acid and choline metabolism.As a result,gut microbiota have been emerging as a novel therapeutic target for NAFLD by manipulating it in various ways,including probiotics,prebiotics,synbiotics,antibiotics,fecal microbiota transplantation,and herbal components.In this review,we summarized the most recent advances in gut microbiota-mediated mechanisms,as well as gut microbiota-targeted therapies on NAFLD.展开更多
OBJECTIVE Although the underlying mechanism is largely unknown,gut dysbiosis has emerged as a central initiator of obesity-related diseases including nonalcoholic fatty liver disease(NAFLD),type 2 diabetes and metabol...OBJECTIVE Although the underlying mechanism is largely unknown,gut dysbiosis has emerged as a central initiator of obesity-related diseases including nonalcoholic fatty liver disease(NAFLD),type 2 diabetes and metabolic syndrome.The emerging evidence support the use of prebiotics like herb-derived polysaccharides for treating NAFLD by modulating gut microbiome.So,our study focused on the microbiota-dependent anti-NAFLD effect and the exact mechanisms of Astragalus polysaccharides(APS)extracted from Astragalus mongholicus Bunge in high-fat diet(HFD)fed mice.METHODS Co-housing experiment was used to assess the microbiota dependent anti-NAFLD effect of APS.Then,targeted metabolomics and metagenomics were adopted for determining short-chain fatty acids(SCFAs)and bacteria that were specifically enriched by APS.Further in vitro experiment was carried out to test the capacity of SCFAs-producing of identified bacterium.Finally,the anti-NAFLD efficacy of identified bacterium was tested in HFD fed mice.RESULTS Our results first demonstrated the anti-NAFLD effect of APS in HFD fed mice and the contribution of gut microbiota.Moreover,our results indicated that SCFAs,predominantly acetic acid were elevated in APS-supplemented mice and ex vivo experiment.Metagenomics revealed that D.vulgaris from Desulfovibrio genus was not only enriched by APS,but also a potent generator of acetic acid,which showed significant anti-NAFLD effects in HFD fed mice.In addition,D.vulgaris modulated the hepatic gene expression pattern of lipids metabolism,particularly suppressed hepatic fatty acid synthase(FASN)and CD36 protein expression.CONCLUSION APS enriched D.vulgaris is effective on attenuating hepatic steatosis possibly through producing acetic acid,and modulation on hepatic lipids metabolism in mice.Further studies are warranted to explore the long-term impacts of D.vulgaris on host metabolism and the underlying mechanism.展开更多
基金National Natural Science Foundation of China (No.81673662) The Program for Professor of Special Appointment (Eastern Scholar)+1 种基金Shuguang Scholar (No. 16SG36)Shanghai Institutions of Higher Learning from Shanghai Municipal Education Commission.
文摘Non-alcoholic fatty liver disease (NAFLD)is one of the most common metabolic diseases currently in the context of obesity worldwide,which contains a spectrum of chronic liver diseases,including hepatic steatosis, non-alcoholic steatohepatitis and hepatic carcinoma.In addition to the classical "Two-hit"theory,NAFLD has been recognized as a typical gut microbiota-related disease because of the intricate role of gut microbiota in maintaining human health and disease formation.Moreover,gut microbiota is even regarded as a "metabolic organ"that play complementary roles to that of liver in many aspects.The mechanisms underlying gut microbiota-mediated development of NAFLD include modulation of host energy metabolism,insulin sensitivity, and bile acid and choline metabolism.As a result,gut microbiota have been emerging as a novel therapeutic target for NAFLD by manipulating it in various ways,including probiotics,prebiotics,synbiotics,antibiotics,fecal microbiota transplantation,and herbal components.In this review,we summarized the most recent advances in gut microbiota-mediated mechanisms,as well as gut microbiota-targeted therapies on NAFLD.
基金National Natural Science Foundation of China(81873059,82004016)。
文摘OBJECTIVE Although the underlying mechanism is largely unknown,gut dysbiosis has emerged as a central initiator of obesity-related diseases including nonalcoholic fatty liver disease(NAFLD),type 2 diabetes and metabolic syndrome.The emerging evidence support the use of prebiotics like herb-derived polysaccharides for treating NAFLD by modulating gut microbiome.So,our study focused on the microbiota-dependent anti-NAFLD effect and the exact mechanisms of Astragalus polysaccharides(APS)extracted from Astragalus mongholicus Bunge in high-fat diet(HFD)fed mice.METHODS Co-housing experiment was used to assess the microbiota dependent anti-NAFLD effect of APS.Then,targeted metabolomics and metagenomics were adopted for determining short-chain fatty acids(SCFAs)and bacteria that were specifically enriched by APS.Further in vitro experiment was carried out to test the capacity of SCFAs-producing of identified bacterium.Finally,the anti-NAFLD efficacy of identified bacterium was tested in HFD fed mice.RESULTS Our results first demonstrated the anti-NAFLD effect of APS in HFD fed mice and the contribution of gut microbiota.Moreover,our results indicated that SCFAs,predominantly acetic acid were elevated in APS-supplemented mice and ex vivo experiment.Metagenomics revealed that D.vulgaris from Desulfovibrio genus was not only enriched by APS,but also a potent generator of acetic acid,which showed significant anti-NAFLD effects in HFD fed mice.In addition,D.vulgaris modulated the hepatic gene expression pattern of lipids metabolism,particularly suppressed hepatic fatty acid synthase(FASN)and CD36 protein expression.CONCLUSION APS enriched D.vulgaris is effective on attenuating hepatic steatosis possibly through producing acetic acid,and modulation on hepatic lipids metabolism in mice.Further studies are warranted to explore the long-term impacts of D.vulgaris on host metabolism and the underlying mechanism.
