ZHOU Wenhui,ZHAO Mei,ZHANG Meng,et al.Exploring Chinese materia medica in the treatment of metabolic associated fatty liver disease based on "gut microbiota⁃bile acid⁃Farnesoid X receptor"[J].Shanghai Journal of Traditional Chinese Medicine,2025,59(6):89-93.
ZHOU Wenhui,ZHAO Mei,ZHANG Meng,et al.Exploring Chinese materia medica in the treatment of metabolic associated fatty liver disease based on "gut microbiota⁃bile acid⁃Farnesoid X receptor"[J].Shanghai Journal of Traditional Chinese Medicine,2025,59(6):89-93. DOI: 10.16305/j.1007-1334.2025.z20241104001.
Exploring Chinese materia medica in the treatment of metabolic associated fatty liver disease based on "gut microbiota⁃bile acid⁃Farnesoid X receptor"
The pathogenesis of metabolic associated fatty liver disease (MAFLD) is complex. Dysregulation of the enterohepatic circulation is not only a key mechanism causing MAFLD, but also an important factor contributing to abnormal bile acid (BA) metabolism and gut microbiota dysbiosis. BA metabolism and the gut microbiota can bidirectionally regulate the enterohepatic circulation through the "gut-liver axis". The Farnesoid X receptor (FXR), the natural ligand of BA, regulates BA synthesis and transport via multiple pathways. We explore the regulatory effects of Chinese materia medica on MAFLD based on the "gut microbiota-BA-FXR" axis. Chinese materia medica can modulate the composition and function of the gut microbiota, as well as regulate FXR-related pathways, thereby maintaining BA balance, improving glucose and lipid metabolism, and alleviating inflammatory responses.
关键词
Keywords
references
XUE R , SU L , LAI S , et al . Bile acid receptors and the gut-liver axis in nonalcoholic fatty liver disease [J]. Cells , 2021 , 10 ( 11 ): 2806 .
JIAO T Y , MA Y D , GUO X Z , et al . Bile acid and receptors: biology and drug discovery for nonalcoholic fatty liver disease [J]. Acta Pharmacol Sin , 2022 , 43 ( 5 ): 1103 - 1119 .
GOTTLIEB A , CANBAY A . Why bile acids are so important in non-alcoholic fatty liver disease(NAFLD) progression [J]. Cells , 2019 , 8 ( 11 ): 1358 .
XIANG J , ZHANG Z , XIE H , et al . Effect of different bile acids on the intestine through enterohepatic circulation based on FXR [J]. Gut Microbes , 2021 , 13 ( 1 ): 1949095 .
PERINO A , DEMAGNY H , VELAZQUEZ-VILLEGAS L , et al . Molecular physiology of bile acid signaling in health, disease, and aging [J]. Physiol Rev , 2021 , 101 ( 2 ): 683 - 731 .
LIN S , WANG S , WANG P , et al . Bile acids and their receptors in regulation of gut health and diseases [J]. Prog Lipid Res , 2023 , 89 : 101210 .
CHIANG J Y L , FERRELL J M . Discovery of farnesoid X receptor and its role in bile acid metabolism [J]. Mol Cell Endocrinol , 2022 , 548 : 111618 .
LI Z , YUAN H , CHU H , et al . The crosstalk between gut microbiota and bile acids promotes the development of non-alcoholic fatty liver disease [J]. Microorganisms , 2023 , 11 ( 8 ): 2059 .
YANG Z , DANZENG A , LIU Q , et al . The role of nuclear receptors in the pathogenesis and treatment of non-alcoholic fatty liver disease [J]. Int J Biol Sci , 2024 , 20 ( 1 ): 113 - 126 .
ZHOU W , ANAKK S . Enterohepatic and non-canonical roles of farnesoid X receptor in controlling lipid and glucose metabolism [J]. Mol Cell Endocrinol , 2022 , 549 : 111616 .
CHEN J , VITETTA L . Gut microbiota metabolites in NAFLD pathogenesis and therapeutic implications [J]. Int J Mol Sci , 2020 , 21 ( 15 ): 5214 .
KRIAA A , BOURGIN M , POTIRON A , et al . Microbial impact on cholesterol and bile acid metabolism:current status and future prospects [J]. J Lipid Res , 2019 , 60 ( 2 ): 323 - 332 .
CAI J , RIMAL B , JIANG C , et al . Bile acid metabolism and signaling, the microbiota, and metabolic disease [J]. Pharmacol Ther , 2022 , 237 : 108238 .
JIANG L Y , ZHANG H J , XIAO D S , et al . Farnesoid X receptor (FXR): Structures and ligands [J]. Comput Struct Biotechnol J , 2021 , 19 : 2148 - 2159 .
GUO X , OKPARA E S , HU W , et al . Interactive relationships between intestinal flora and bile acids [J]. Int J Mol Sci , 2022 , 23 ( 15 ): 8343 .
SHI Q , YUAN X , ZENG Y , et al . Crosstalk between gut microbiota and bile acids in cholestatic liver disease [J]. Nutrients , 2023 , 15 ( 10 ): 2411 .
WANG S , DONG W , LIU L , et al . Interplay between bile acids and the gut microbiota promotes intestinal carcinogenesis [J]. Mol Carcinog , 2019 , 58 ( 7 ): 1155 - 1167 .
LI T , CHIANG J Y . Bile acid signaling in metabolic disease and drug therapy [J]. Pharmacol Rev , 2014 , 66 ( 4 ): 948 - 983 .
HOU J J , WANG X , WANG Y M , et al . Interplay between gut microbiota and bile acids in diarrhoea-predominant irritable bowel syndrome:a review [J]. Crit Rev Microbiol , 2022 , 48 ( 6 ): 696 - 713 .
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 .
WINSTON J A , THERIOT C M . Diversification of host bile acids by members of the gut microbiota [J]. Gut Microbes , 2020 , 11 ( 2 ): 158 - 171 .
MORI H , SVEGLIATI BARONI G , MARZIONI M , et al . Farnesoid X receptor, bile acid metabolism, and gut microbiota [J]. Metabolites , 2022 , 12 ( 7 ): 647 .
CHEN J , THOMSEN M , VITETTA L . Interaction of gut microbiota with dysregulation of bile acids in the pathogenesis of nonalcoholic fatty liver disease and potential therapeutic implications of probiotics [J]. J Cell Biochem , 2019 , 120 ( 3 ): 2713 - 2720 .
ADORINI L , TRAUNER M . FXR agonists in NASH treatment [J]. J Hepatol , 2023 , 79 ( 5 ): 1317 - 1331 .
TILG H , ADOLPH T E , TRAUNER M . Gut-liver axis: Pathophysiological concepts and clinical implications [J]. Cell Metab , 2022 , 34 ( 11 ): 1700 - 1718 .
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 .
HUANG J , CHEN P , XIANG Y , et al . Gut microbiota dysbiosis-derived macrophage pyroptosis causes polycystic ovary syndrome via steroidogenesis disturbance and apoptosis of granulosa cells [J]. Int Immunopharmacol , 2022 , 107 : 108717 .
HUANG J , ZHANG J , WANG F , et al . Modified Gegen Qinlian Decoction modulated the gut microbiome and bile acid metabolism and restored the function of goblet cells in a mouse model of ulcerative colitis [J]. Front Immunol , 2024 , 15 : 1445838 .
SUN R , YANG N , KONG B , et al . Orally administered berberine modulates hepatic lipid metabolism by altering microbial bile acid metabolism and the intestinal FXR signaling pathway [J]. Mol Pharmacol , 2017 , 91 ( 2 ): 110 - 122 .
TIAN Y , CAI J , GUI W , et al . Berberine directly affects the gut microbiota to promote intestinal farnesoid X receptor activation [J]. Drug Metab Dispos , 2019 , 47 ( 2 ): 86 - 93 .
SHU X , LI M , CAO Y , et al . Berberine alleviates non-alcoholic steatohepatitis through modulating gut microbiota mediated intestinal FXR activation [J]. Front Pharmacol , 2021 , 12 : 750826 .
GU M , SONG H , LI Y , et al . Extract of Schisandra chinensis fruit protects against metabolic dysfunction in high-fat diet induced obese mice via FXR activation [J]. Phytother Res , 2020 , 34 ( 11 ): 3063 - 3077 .
CHENG N , CHEN S , LIU X , et al . Impact of Schisandra Chinensis Bee Pollen on nonalcoholic fatty liver disease and gut microbiota in highfat diet induced obese mice [J]. Nutrients , 2019 , 11 ( 2 ): 346 .
CAI F F , WU R , SONG Y N , et al . Yinchenhao Decoction alleviates liver fibrosis by regulating bile acid metabolism and TGF-β/Smad/ERK signalling pathway [J]. Sci Rep , 2018 , 8 ( 1 ): 15367 .
Research progress on immunomodulatory mechanisms of Chinese materia medica in intervening liver cirrhosis via regulating gut microbiota and its metabolites
Experience on treating damp‑heat accumulation syndrome in metabolic associated fatty liver disease with herbal pair of Tufuling and Shengtoucao
Research progress in exploring mechanism of Chinese materia medica in treating osteoporosis based on H‑type blood vessels
Application prospects and challenges of generative artificial intelligence in standardization of traditional Chinese medicine
Research progress on regulation of ferroptosis by traditional Chinese herbal medicine in treatment of metabolic dysfunction⁃associated steatotic liver disease
Related Author
GAO Xiaodi
LU Yi
XU Yumin
ZHU Junfeng
SHI Jia
YU Zhuo
LIU Desun
FAN Jiaxuan
Related Institution
Department of Infectious Diseases, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Department of Infectious Diseases, Children's Hospital of Fudan University
Department of Hepatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine
Department of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine
Institute of Infectious Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine