Bile acid metabolism in the gut-liver axis and its regulatory role in chronic liver disease_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

BO Jiayi ¹ ,  GUO Yong ² ,  GONG Jianping ¹

1. Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P. R. China;
2. Chongqing Changshou District People’s Hospital, Chongqing 401220, P. R. China;

Corresponding?author：

GUO Yong, Email: 21617675@qq.com; GONG Jianping, Email: gongjianping11@126.com

Keywords：

chronic liver disease; bile acids; gut-liver axis; gut microbiota

DOI：

10.7507/1007-9424.202606027

Video：

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Objective To systematically review the mechanisms of the gut microbiota-bile acid axis in chronic liver disease and related targeted therapeutic strategies, providing a theoretical basis for the diagnosis and treatment of chronic liver disease. Methods Relevant domestic and international literature on bile acid synthesis and metabolism, key receptor signaling pathways, gut microbiota-bile acid interactions and its relationships with chronic liver disease were retrieved and reviewed. Results Bile acids regulate glucose and lipid metabolism, energy homeostasis, immune and inflammatory responses, and intestinal barrier function by activating receptors such as farnesoid X receptor (FXR) and takeda G protein-coupled receptor 5 (TGR5). Gut microbiota participates in bile acid metabolic transformation through deconjugation, dehydroxylation and epimerization reaction, and the two form the gut microbiota-bile acid axis. Dysregulation of this axis can disrupt bile acid metabolism and is closely associated with the development of chronic liver diseases. Therapeutic strategies targeting the gut microbiota-bile acid axis include FXR agonists, TGR5 agonists, bile acid derivatives and gut microbiota modulation. Conclusions Bile acids are important signaling molecules in the gut-liver axis and participate in regulating the pathological processes of chronic liver disease through FXR, TGR5, and their downstream pathways. Targeting metabolic transformations and receptor signaling pathways related to the gut microbiota-bile acid axis has considerable translational potential.

Citation： BO Jiayi, GUO Yong, GONG Jianping. Bile acid metabolism in the gut-liver axis and its regulatory role in chronic liver disease. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2026, 33(8): 1127-1134. doi: 10.7507/1007-9424.202606027 Copy

1.	Fuchs CD, Simbrunner B, Baumgartner M, et al. Bile acid metabolism and signalling in liver disease [J]. J Hepatol, 2025, 82(1): 134-153.
2.	Devarbhavi H, Asrani SK, Arab JP, et al. Global burden of liver disease: 2023 update [J]. J Hepatol, 2023, 79(2): 516-537.
3.	Riazi K, Azhari H, Charette JH, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis [J]. Lancet Gastroenterol Hepatol, 2022, 7(9): 851-861.
4.	Fleishman JS, Kumar S. Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets [J/OL]. Signal Transduct Target Ther, 2024, 9(1): 97. doi: 10.1038/s41392-024-01811-6.
5.	Li T, Chiang JYL. Bile acid signaling in metabolic and inflammatory diseases and drug development [J]. Pharmacol Rev, 2024, 76(6): 1221-1253.
6.	Mohanty I, Allaband C, Mannochio-Russo H, et al. The changing metabolic landscape of bile acids - keys to metabolism and immune regulation [J]. Nat Rev Gastroenterol Hepatol, 2024, 21(7): 493-516.
7.	Ridlon JM, Gaskins HR. Another renaissance for bile acid gastrointestinal microbiology [J]. Nat Rev Gastroenterol Hepatol, 2024, 21(5): 348-364.
8.	Collins SL, Stine JG, Bisanz JE, et al. Bile acids and the gut microbiota: metabolic interactions and impacts on disease [J]. Nat Rev Microbiol, 2023, 21(4): 236-247.
9.	Mori H, Svegliati Baroni G, Marzioni M, et al. Farnesoid X receptor, bile acid metabolism, and gut microbiota [J/OL]. Metabolites, 2022, 12(7): 647. doi: 10.3390/metabo12070647.
10.	Tian Y, Gui W, Koo I, et al. The microbiome modulating activity of bile acids [J]. Gut Microbes, 2020, 11(4): 979-996.
11.	Ding C, Wang Z, Dou X, et al. Farnesoid X receptor: from structure to function and its pharmacology in liver fibrosis [J]. Aging Dis, 2024, 15(4): 1508-1536.
12.	Adorini L, Trauner M. FXR agonists in NASH treatment [J]. J Hepatol, 2023, 79(5): 1317-1331.
13.	Wang W, Li L, Li X, et al. FXR overexpression alleviates cholestasis via NLRC4 inflammasome suppression and bile acid homeostasis regulation [J]. Free Radic Biol Med, 2025, 238: 152-168.
14.	Anis MA, Shahid Y, Majeed AA, et al. Microbiome and gut-liver interactions: from mechanisms to therapies [J/OL]. World J Gastroenterol, 2025, 31(40): 111409. doi: 10.3748/wjg.v31.i40.111409.
15.	Yan W, Zhang K, Guo J, et al. Bile acid-mediated gut-liver axis crosstalk: the role of nuclear receptor signaling in dynamic regulation of inflammatory networks[J]. Front Immunol, 2025, 16: 1595486. doi: 10.3389/fimmu.2025.1595486.
16.	Biagioli M, Marchianò S, Di Giorgio C, et al. Secondary bile acids and host metabolism: crosstalk, signaling pathways and therapeutic frontiers [J]. Eur Rev Med Pharmacol Sci, 2025, 29(12): 587-599.
17.	趙帥華, 張先舟, 蒙博, 等. 肝內膽管癌組織膽汁酸G蛋白偶聯受體5和熱休克蛋白75表達及與預后的關系 [J]. 中國普外基礎與臨床雜志, 2022, 29(2): 218-225.
18.	Tyagi A, Kumar V. The gut microbiota-bile acid axis: a crucial regulator of immune function and metabolic health [J/OL]. World J Microbiol Biotechnol, 2025, 41(7): 215. doi: 10.1007/s11274-025-04395-7.
19.	Chen F, Gong L. Bile acid-microbiota interactions in cardiometabolic diseases: mechanisms and emerging therapeutic approaches [J/OL]. Front Microbiol, 2025 , 16: 1689026. doi: 10.3389/fmicb.2025.1689026.
20.	Smirnova E, Muthiah MD, Narayan N, et al. Metabolic reprogramming of the intestinal microbiome with functional bile acid changes underlie the development of NAFLD [J]. Hepatology, 2022, 76(6): 1811-1824.
21.	趙昊, 南博元, 張巍. 兩樣本孟德爾隨機化分析腸道菌群與膽石癥的因果關系 [J]. 中國普外基礎與臨床雜志, 2025, 32(8): 972-977.
22.	Liu J, Wu A, Cai J, et al. The contribution of the gut-liver axis to the immune signaling pathway of NAFLD [J/OL]. Front Immunol, 2022, 13: 968799. doi: 10.3389/fimmu.2022.968799.
23.	Kuang J, Wang J, Li Y, et al. Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis [J]. Cell Metab, 2023, 35(10): 1752-1766.
24.	Wang Y, Chen X, Huws SA, et al. Ileal microbial microbiome and its secondary bile acids modulate susceptibility to nonalcoholic steatohepatitis in dairy goats [J/OL]. Microbiome, 2024, 12(1): 247. doi: 10.1186/s40168-024-01964-0.
25.	Harrison SA, Rinella ME, Abdelmalek MF, et al. NGM282 for treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial [J]. Lancet, 2018, 391(10126): 1174-1185.
26.	Yan C, Hu W, Tu J, et al. Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease [J/OL]. J Transl Med, 2023, 21(1): 300. doi: 10.1186/s12967-023-04166-8.
27.	Hartmann P, Hochrath K, Horvath A, et al. Modulation of the intestinal bile acid/farnesoid X receptor/fibroblast growth factor 15 axis improves alcoholic liver disease in mice [J]. Hepatology, 2018, 67(6): 2150-2166.
28.	Jung JH, Kim SE, Suk KT, et al. Gut microbiota-modulating agents in alcoholic liver disease: links between host metabolism and gut microbiota [J/OL]. Front Med (Lausanne), 2022, 9: 913842. doi: 10.3389/fmed.2022.913842.
29.	Xiang H, Liu Z, Xiang H, et al. Dynamics of the gut-liver axis in rats with varying fibrosis severity [J]. Int J Biol Sci, 2022, 18(8): 3390-3404.
30.	Chang L, Liu Y, Li H, et al. Gut microbiome and its metabolites in liver cirrhosis: mechanisms and clinical implications [J/OL]. Front Cell Infect Microbiol, 2025, 15: 1717696. doi: 10.3389/fcimb.2025.1717696.
31.	Hao Y, Hao Z, Zeng X, et al. Gut microbiota and metabolites of cirrhotic portal hypertension: a novel target on the therapeutic regulation [J]. J Gastroenterol, 2024, 59(9): 788-797.
32.	Zeng J, Fan J, Zhou H. Bile acid-mediated signaling in cholestatic liver diseases [J/OL]. Cell Biosci, 2023, 13(1): 77. doi: 10.1186/s13578-023-01035-1.
33.	Liu X, Li J, Shi M, et al. Melatonin improves cholestatic liver disease via the gut-liver axis [J/OL]. J Pineal Res, 2024, 76(1): e12929. doi: 10.1111/jpi.12929.
34.	Cariello M, Gadaleta RM, Moschetta A. The gut-liver axis in cholangiopathies: focus on bile acid based pharmacological treatment [J]. Curr Opin Gastroenterol, 2022, 38(2): 136-143.
35.	Schneider KM, Mohs A, Gui W, et al. Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment [J/OL]. Nat Commun, 2022, 13(1): 3964. doi: 10.1038/s41467-022-31312-5.
36.	Yan ZB, Han CL, Jia JS, et al. The landscape of gut microbiota in hepatocarcinogenesis: a comprehensive review of pathogenesis and therapeutic interventions [J]. Int J Surg, 2026, 112(1): 1673-1695.
37.	Song Y, Lau HC, Zhang X, et al. Bile acids, gut microbiota, and therapeutic insights in hepatocellular carcinoma [J]. Cancer Biol Med, 2023, 21(2): 144-162.
38.	鄭燕, 徐齡聰, 周永強, 等. 腸道菌群通過調節腫瘤微環境影響肝癌的發生 [J]. 中國普外基礎與臨床雜志, 2024, 31(4): 502-507.
39.	Nevens F, Andreone P, Mazzella G, et al. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis [J]. N Engl J Med, 2016, 375(7): 631-643.
40.	Liu J, Sun J, Yu J, et al. Gut microbiome determines therapeutic effects of OCA on NAFLD by modulating bile acid metabolism [J/OL]. NPJ Biofilms Microbiomes, 2023, 9(1): 29. doi: 10.1038/s41522-023-00399-z.
41.	Wang XX, Xie C, Libby AE, et al. The role of FXR and TGR5 in reversing and preventing progression of Western diet-induced hepatic steatosis, inflammation, and fibrosis in mice [J/OL]. J Biol Chem, 2022, 298(11): 102530. doi: 10.1016/j.jbc.2022.102530.
42.	Fickert P, Hirschfield GM, Denk G, et al. norUrsodeoxycholic acid improves cholestasis in primary sclerosing cholangitis [J]. J Hepatol, 2017, 67(3): 549-558.
43.	Zhang M, Xiao B, Chen X, et al. Physical exercise plays a role in rebalancing the bile acids of enterohepatic axis in non-alcoholic fatty liver disease [J/OL]. Acta Physiol (Oxf), 2024, 240(1): e14065. doi: 10.1111/apha.14065.
44.	Che Z, Xue W, Zhao X, et al. Regulatory role and biomarker potential of gut microbiota metabolites in the progression of metabolic dysfunction-associated steatotic liver disease to hepatocellular carcinoma [J/OL]. Clin Transl Gastroenterol, 2025, 16(12): e00914. doi: 10.14309/ctg.0000000000000914.

1. Fuchs CD, Simbrunner B, Baumgartner M, et al. Bile acid metabolism and signalling in liver disease [J]. J Hepatol, 2025, 82(1): 134-153.
2. Devarbhavi H, Asrani SK, Arab JP, et al. Global burden of liver disease: 2023 update [J]. J Hepatol, 2023, 79(2): 516-537.
3. Riazi K, Azhari H, Charette JH, et al. The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis [J]. Lancet Gastroenterol Hepatol, 2022, 7(9): 851-861.
4. Fleishman JS, Kumar S. Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets [J/OL]. Signal Transduct Target Ther, 2024, 9(1): 97. doi: 10.1038/s41392-024-01811-6.
5. Li T, Chiang JYL. Bile acid signaling in metabolic and inflammatory diseases and drug development [J]. Pharmacol Rev, 2024, 76(6): 1221-1253.
6. Mohanty I, Allaband C, Mannochio-Russo H, et al. The changing metabolic landscape of bile acids - keys to metabolism and immune regulation [J]. Nat Rev Gastroenterol Hepatol, 2024, 21(7): 493-516.
7. Ridlon JM, Gaskins HR. Another renaissance for bile acid gastrointestinal microbiology [J]. Nat Rev Gastroenterol Hepatol, 2024, 21(5): 348-364.
8. Collins SL, Stine JG, Bisanz JE, et al. Bile acids and the gut microbiota: metabolic interactions and impacts on disease [J]. Nat Rev Microbiol, 2023, 21(4): 236-247.
9. Mori H, Svegliati Baroni G, Marzioni M, et al. Farnesoid X receptor, bile acid metabolism, and gut microbiota [J/OL]. Metabolites, 2022, 12(7): 647. doi: 10.3390/metabo12070647.
10. Tian Y, Gui W, Koo I, et al. The microbiome modulating activity of bile acids [J]. Gut Microbes, 2020, 11(4): 979-996.
11. Ding C, Wang Z, Dou X, et al. Farnesoid X receptor: from structure to function and its pharmacology in liver fibrosis [J]. Aging Dis, 2024, 15(4): 1508-1536.
12. Adorini L, Trauner M. FXR agonists in NASH treatment [J]. J Hepatol, 2023, 79(5): 1317-1331.
13. Wang W, Li L, Li X, et al. FXR overexpression alleviates cholestasis via NLRC4 inflammasome suppression and bile acid homeostasis regulation [J]. Free Radic Biol Med, 2025, 238: 152-168.
14. Anis MA, Shahid Y, Majeed AA, et al. Microbiome and gut-liver interactions: from mechanisms to therapies [J/OL]. World J Gastroenterol, 2025, 31(40): 111409. doi: 10.3748/wjg.v31.i40.111409.
15. Yan W, Zhang K, Guo J, et al. Bile acid-mediated gut-liver axis crosstalk: the role of nuclear receptor signaling in dynamic regulation of inflammatory networks[J]. Front Immunol, 2025, 16: 1595486. doi: 10.3389/fimmu.2025.1595486.
16. Biagioli M, Marchianò S, Di Giorgio C, et al. Secondary bile acids and host metabolism: crosstalk, signaling pathways and therapeutic frontiers [J]. Eur Rev Med Pharmacol Sci, 2025, 29(12): 587-599.
17. 趙帥華, 張先舟, 蒙博, 等. 肝內膽管癌組織膽汁酸G蛋白偶聯受體5和熱休克蛋白75表達及與預后的關系 [J]. 中國普外基礎與臨床雜志, 2022, 29(2): 218-225.
18. Tyagi A, Kumar V. The gut microbiota-bile acid axis: a crucial regulator of immune function and metabolic health [J/OL]. World J Microbiol Biotechnol, 2025, 41(7): 215. doi: 10.1007/s11274-025-04395-7.
19. Chen F, Gong L. Bile acid-microbiota interactions in cardiometabolic diseases: mechanisms and emerging therapeutic approaches [J/OL]. Front Microbiol, 2025 , 16: 1689026. doi: 10.3389/fmicb.2025.1689026.
20. Smirnova E, Muthiah MD, Narayan N, et al. Metabolic reprogramming of the intestinal microbiome with functional bile acid changes underlie the development of NAFLD [J]. Hepatology, 2022, 76(6): 1811-1824.
21. 趙昊, 南博元, 張巍. 兩樣本孟德爾隨機化分析腸道菌群與膽石癥的因果關系 [J]. 中國普外基礎與臨床雜志, 2025, 32(8): 972-977.
22. Liu J, Wu A, Cai J, et al. The contribution of the gut-liver axis to the immune signaling pathway of NAFLD [J/OL]. Front Immunol, 2022, 13: 968799. doi: 10.3389/fimmu.2022.968799.
23. Kuang J, Wang J, Li Y, et al. Hyodeoxycholic acid alleviates non-alcoholic fatty liver disease through modulating the gut-liver axis [J]. Cell Metab, 2023, 35(10): 1752-1766.
24. Wang Y, Chen X, Huws SA, et al. Ileal microbial microbiome and its secondary bile acids modulate susceptibility to nonalcoholic steatohepatitis in dairy goats [J/OL]. Microbiome, 2024, 12(1): 247. doi: 10.1186/s40168-024-01964-0.
25. Harrison SA, Rinella ME, Abdelmalek MF, et al. NGM282 for treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial [J]. Lancet, 2018, 391(10126): 1174-1185.
26. Yan C, Hu W, Tu J, et al. Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease [J/OL]. J Transl Med, 2023, 21(1): 300. doi: 10.1186/s12967-023-04166-8.
27. Hartmann P, Hochrath K, Horvath A, et al. Modulation of the intestinal bile acid/farnesoid X receptor/fibroblast growth factor 15 axis improves alcoholic liver disease in mice [J]. Hepatology, 2018, 67(6): 2150-2166.
28. Jung JH, Kim SE, Suk KT, et al. Gut microbiota-modulating agents in alcoholic liver disease: links between host metabolism and gut microbiota [J/OL]. Front Med (Lausanne), 2022, 9: 913842. doi: 10.3389/fmed.2022.913842.
29. Xiang H, Liu Z, Xiang H, et al. Dynamics of the gut-liver axis in rats with varying fibrosis severity [J]. Int J Biol Sci, 2022, 18(8): 3390-3404.
30. Chang L, Liu Y, Li H, et al. Gut microbiome and its metabolites in liver cirrhosis: mechanisms and clinical implications [J/OL]. Front Cell Infect Microbiol, 2025, 15: 1717696. doi: 10.3389/fcimb.2025.1717696.
31. Hao Y, Hao Z, Zeng X, et al. Gut microbiota and metabolites of cirrhotic portal hypertension: a novel target on the therapeutic regulation [J]. J Gastroenterol, 2024, 59(9): 788-797.
32. Zeng J, Fan J, Zhou H. Bile acid-mediated signaling in cholestatic liver diseases [J/OL]. Cell Biosci, 2023, 13(1): 77. doi: 10.1186/s13578-023-01035-1.
33. Liu X, Li J, Shi M, et al. Melatonin improves cholestatic liver disease via the gut-liver axis [J/OL]. J Pineal Res, 2024, 76(1): e12929. doi: 10.1111/jpi.12929.
34. Cariello M, Gadaleta RM, Moschetta A. The gut-liver axis in cholangiopathies: focus on bile acid based pharmacological treatment [J]. Curr Opin Gastroenterol, 2022, 38(2): 136-143.
35. Schneider KM, Mohs A, Gui W, et al. Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment [J/OL]. Nat Commun, 2022, 13(1): 3964. doi: 10.1038/s41467-022-31312-5.
36. Yan ZB, Han CL, Jia JS, et al. The landscape of gut microbiota in hepatocarcinogenesis: a comprehensive review of pathogenesis and therapeutic interventions [J]. Int J Surg, 2026, 112(1): 1673-1695.
37. Song Y, Lau HC, Zhang X, et al. Bile acids, gut microbiota, and therapeutic insights in hepatocellular carcinoma [J]. Cancer Biol Med, 2023, 21(2): 144-162.
38. 鄭燕, 徐齡聰, 周永強, 等. 腸道菌群通過調節腫瘤微環境影響肝癌的發生 [J]. 中國普外基礎與臨床雜志, 2024, 31(4): 502-507.
39. Nevens F, Andreone P, Mazzella G, et al. A placebo-controlled trial of obeticholic acid in primary biliary cholangitis [J]. N Engl J Med, 2016, 375(7): 631-643.
40. Liu J, Sun J, Yu J, et al. Gut microbiome determines therapeutic effects of OCA on NAFLD by modulating bile acid metabolism [J/OL]. NPJ Biofilms Microbiomes, 2023, 9(1): 29. doi: 10.1038/s41522-023-00399-z.
41. Wang XX, Xie C, Libby AE, et al. The role of FXR and TGR5 in reversing and preventing progression of Western diet-induced hepatic steatosis, inflammation, and fibrosis in mice [J/OL]. J Biol Chem, 2022, 298(11): 102530. doi: 10.1016/j.jbc.2022.102530.
42. Fickert P, Hirschfield GM, Denk G, et al. norUrsodeoxycholic acid improves cholestasis in primary sclerosing cholangitis [J]. J Hepatol, 2017, 67(3): 549-558.
43. Zhang M, Xiao B, Chen X, et al. Physical exercise plays a role in rebalancing the bile acids of enterohepatic axis in non-alcoholic fatty liver disease [J/OL]. Acta Physiol (Oxf), 2024, 240(1): e14065. doi: 10.1111/apha.14065.
44. Che Z, Xue W, Zhao X, et al. Regulatory role and biomarker potential of gut microbiota metabolites in the progression of metabolic dysfunction-associated steatotic liver disease to hepatocellular carcinoma [J/OL]. Clin Transl Gastroenterol, 2025, 16(12): e00914. doi: 10.14309/ctg.0000000000000914.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Bile acid metabolism in the gut-liver axis and its regulatory role in chronic liver disease

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