Novel pathogenesis and intervention strategies for liver cirrhosis based on the gut microbiota-bile acid axis

Ningning LIU; Wenting CUI; Shuli MU; Xiuzhen MA; Ping MAI

doi:10.12449/JCH260330

Volume 42 Issue 3

Mar. 2026

Turn off MathJax

Article Contents

Article Navigation > Journal of Clinical Hepatology > 2026 > 42(3): 718-725

PDF( 743 KB)

Novel pathogenesis and intervention strategies for liver cirrhosis based on the gut microbiota-bile acid axis

DOI: 10.12449/JCH260330

Ningning LIU^{1, 2},
Wenting CUI^{1, 2},
Shuli MU^{1, 2},
Xiuzhen MA^{2, 3},
Ping MAI^{2
,
,
,}

1.
The First Clinical Medical College of Gansu University of Chinese Medicine，Lanzhou 730000，China
2.
Department of Gastroenterology，Gansu Provincial Hospital，Lanzhou 730000，China
3.
The First Clinical Medical College of Lanzhou University，Lanzhou 730000，China

Research funding:

Natural Science Foundation of Gansu Province (21JR1RA014)

More Information

Corresponding author: MAI Ping， maiping_123@163.com （ORCID： 0000-0003-3706-7439）
Received Date: 2025-06-24
Accepted Date: 2025-08-20
Published Date: 2026-03-25

Abstract

Abstract

Liver cirrhosis is the final stage of the progression of various chronic liver diseases， often accompanied by serious complications and high mortality rates. Recent studies have shown that the interaction between gut microbiota and bile acid metabolism （the gut microbiota-bile acid axis） is closely associated with liver cirrhosis. This article systematically reviews the mechanism of action of the gut microbiota-bile acid axis in the progression of liver cirrhosis， elaborates on the pathological features of liver cirrhosis and its harm to the body， and summarizes the association of the gut microbiota-bile acid axis with the development and progression of liver cirrhosis. It also analyzes the key regulatory role of this axis in the progression of liver cirrhosis and explores its potential application value as a therapeutic target for liver cirrhosis， in order to provide a theoretical basis for exploring more effective clinical intervention methods.
- Liver Cirrhosis,
- Gastrointestinal Microbiome,
- Bile Acid

FullText(HTML)

References(66)

References

[1]	XIAO NQ, ZHANG XY, XI YJ, et al. Study on the effects of intestinal flora on gouty arthritis[J]. Front Cell Infect Microbiol, 2024, 14: 1341953. DOI: 10.3389/fcimb.2024.1341953.
[2]	PLUTA R, JANUSZEWSKI S, CZUCZWAR SJ. The role of gut microbiota in an ischemic stroke[J]. Int J Mol Sci, 2021, 22( 2): 915. DOI: 10.3390/ijms22020915.
[3]	QIU P, ISHIMOTO T, FU LF, et al. The gut microbiota in inflammatory bowel disease[J]. Front Cell Infect Microbiol, 2022, 12: 733992. DOI: 10.3389/fcimb.2022.733992.
[4]	VOURAKIS M, MAYER G, ROUSSEAU G. The role of gut microbiota on cholesterol metabolism in atherosclerosis[J]. Int J Mol Sci, 2021, 22( 15): 8074. DOI: 10.3390/ijms22158074.
[5]	PAONE P, CANI PD. Mucus barrier, mucins and gut microbiota: The expected slimy partners?[J]. Gut, 2020, 69( 12): 2232- 2243. DOI: 10.1136/gutjnl-2020-322260.
[6]	CHUNG J, LEE JC, OH H, et al. Gut microbiota regulates the homeostasis of dendritic epidermal T cells[J]. Life, 2024, 14( 12): 1695. DOI: 10.3390/life14121695.
[7]	de AGUIAR VALLIM TQ, TARLING EJ, EDWARDS PA. Pleiotropic roles of bile acids in metabolism[J]. Cell Metab, 2013, 17( 5): 657- 669. DOI: 10.1016/j.cmet.2013.03.013.
[8]	WOOTON-KEE CR, YALAMANCHILI HK, MOHAMED I, et al. Changes in the FXR-cistrome and alterations in bile acid physiology in Wilson disease[J]. Hepatol Commun, 2025, 9( 6): e0707. DOI: 10.1097/HC9.00-00000000000707.
[9]	GHALLAB A, MANDORFER M, STIRNIMANN G, et al. Enteronephrohepatic circulation of bile acids and therapeutic potential of systemic bile acid transporter inhibitors[J]. J Hepatol, 2025, 83( 5): 1204- 1217. DOI: 10.1016/j.jhep.2025.05.009.
[10]	LIN S, WANG ST, WANG P, et al. Bile acids and their receptors in regulation of gut health and diseases[J]. Prog Lipid Res, 2023, 89: 101210. DOI: 10.1016/j.plipres.2022.101210.
[11]	di GREGORIO MC, CAUTELA J, GALANTINI L. Physiology and physical chemistry of bile acids[J]. Int J Mol Sci, 2021, 22( 4): 1780. DOI: 10.3390/ijms22041780.
[12]	SHARMA B, TWELKER K, NGUYEN C, et al. Bile acids in pancreatic carcinogenesis[J]. Metabolites, 2024, 14( 7): 348. DOI: 10.3390/metabo14070348.
[13]	REŽEN T, ROZMAN D, KOVÁCS T, et al. The role of bile acids in carcinogenesis[J]. Cell Mol Life Sci, 2022, 79( 5): 243. DOI: 10.1007/s00018-022-04278-2.
[14]	VISEKRUNA A, LUU M. The role of short-chain fatty acids and bile acids in intestinal and liver function, inflammation, and carcinogenesis[J]. Front Cell Dev Biol, 2021, 9: 703218. DOI: 10.3389/fcell.2021.703218.
[15]	LEI X, CUI ZY, HUANG XJ. Exploration of gastric carcinogenesis from the relationship between bile acids and intestinal Metaplasia and intragastric microorganisms(H. pylori and non-H. pylori)[J]. J Cancer Res Clin Oncol, 2023, 149( 18): 16947- 16956. DOI: 10.1007/s00432-023-05407-5.
[16]	WANG X, CHEN HZ, LIU WT, et al. The association of plasma high-density lipoprotein cholesterol levels and cirrhosis development in obese patients with chronic hepatitis B: A cohort study[J]. Eur J Gastroenterol Hepatol, 2021, 33( 5): 738- 744. DOI: 10.1097/MEG.000000000-0001965.
[17]	MA YY, YANG HZ, WANG XM, et al. Bile acids as signaling molecules in inflammatory bowel disease: Implications for treatment strategies[J]. J Ethnopharmacol, 2025, 337: 118968. DOI: 10.1016/j.jep.2024.118968.
[18]	LI W, CHEN H, TANG JG. Interplay between bile acids and intestinal microbiota: Regulatory mechanisms and therapeutic potential for infections[J]. Pathogens, 2024, 13( 8): 702. DOI: 10.3390/pathogens13080702.
[19]	LIU P, JIN MP, HU P, et al. Gut microbiota and bile acids: Metabolic interactions and impacts on diabetic kidney disease[J]. Curr Res Microb Sci, 2024, 7: 100315. DOI: 10.1016/j.crmicr.2024.100315.
[20]	ZHANG XP, HU JQ, LI Y, et al. Gallbladder microbial species and host bile acids biosynthesis linked to cholesterol gallstone comparing to pigment individuals[J]. Front Cell Infect Microbiol, 2024, 14: 1283737. DOI: 10.3389/fcimb.2024.1283737.
[21]	HEIDRICH B, VITAL M, PLUMEIER I, et al. Intestinal microbiota in patients with chronic hepatitis C with and without cirrhosis compared with healthy controls[J]. Liver Int, 2018, 38( 1): 50- 58. DOI: 10.1111/liv.13485.
[22]	HRNCIR T, HRNCIROVA L, KVERKA M, et al. Gut microbiota and NAFLD: Pathogenetic mechanisms, microbiota signatures, and therapeutic interventions[J]. Microorganisms, 2021, 9( 5): 957. DOI: 10.33-90/microorganisms9050957.
[23]	ZHOU XP, WU J, HE Q, et al. Short-chain chlorinated paraffins induce liver injury in mice through mitochondrial disorders and disruption of cholesterol-bile acid pathway[J]. Environ Pollut, 2025, 364( Pt 1): 125323. DOI: 10.1016/j.envpol.2024.125323.
[24]	LI Y, KONG MW, JIANG N, et al. Vine tea extract ameliorated acute liver injury by inhibiting hepatic autophagy and reversing abnormal bile acid metabolism[J]. Heliyon, 2023, 9( 9): e20145. DOI: 10.1016/j.heliyon.2023.e20145.
[25]	SHEARN CT, ANDERSON AL, MILLER CG, et al. Thioredoxin reductase 1 regulates hepatic inflammation and macrophage activation during acute cholestatic liver injury[J]. Hepatol Commun, 2023, 7( 1): e0020. DOI: 10.1097/HC9.0000000000000020.
[26]	CANESIN G, FELDBRÜGGE L, WEI GY, et al. Heme oxygenase-1 mitigates liver injury and fibrosis via modulation of LNX1/Notch1 pathway in myeloid cells[J]. iScience, 2022, 25( 9): 104983. DOI: 10.1016/j.isci.2022.104983.
[27]	WU PJ, QIAO L, YU H, et al. Arbutin alleviates the liver injury of α-naphthylisothiocyanate-induced cholestasis through farnesoid X receptor activation[J]. Front Cell Dev Biol, 2021, 9: 758632. DOI: 10.3389/fcell.2021.758632.
[28]	FLEISHMAN JS, KUMAR S. Bile acid metabolism and signaling in health and disease: Molecular mechanisms and therapeutic targets[J]. Signal Transduct Target Ther, 2024, 9( 1): 97. DOI: 10.1038/s41392-024-01811-6.
[29]	TVETER KM, MEZHIBOVSKY E, WU Y, et al. Bile acid metabolism and signaling: Emerging pharmacological targets of dietary polyphenols[J]. Pharmacol Ther, 2023, 248: 108457. DOI: 10.1016/j.pharmthera.2023.108457.
[30]	CAI JW, RIMAL B, JIANG CT, et al. Bile acid metabolism and signaling, the microbiota, and metabolic disease[J]. Pharmacol Ther, 2022, 237: 108238. DOI: 10.1016/j.pharmthera.2022.108238.
[31]	SHULPEKOVA Y, SHIROKOVA E, ZHARKOVA M, et al. A recent ten-year perspective: Bile acid metabolism and signaling[J]. Molecules, 2022, 27( 6): 1983. DOI: 10.3390/molecules27061983.
[32]	BROWNING MG, PESSOA BM, KHORAKI J, et al. Changes in bile acid metabolism, transport, and signaling as central drivers for metabolic improvements after bariatric surgery[J]. Curr Obes Rep, 2019, 8( 2): 175- 184. DOI: 10.1007/s13679-019-00334-4.
[33]	YUAN H, ZHOU JY, WU XG, et al. Enterotype-stratified gut microbial signatures in MASLD and cirrhosis based on integrated microbiome data[J]. Front Microbiol, 2025, 16: 1568672. DOI: 10.3389/fmicb.2025.1568-672.
[34]	CHIANG JYL, FERRELL JM. Bile acid metabolism in liver pathobiology[J]. Gene Expr, 2018, 18( 2): 71- 87. DOI: 10.3727/105221618X15156018385515.
[35]	LIU XP, LIU D, TAN CE, et al. Gut microbiome-based machine learning for diagnostic prediction of liver fibrosis and cirrhosis: A systematic review and meta-analysis[J]. BMC Med Inform Decis Mak, 2023, 23( 1): 294. DOI: 10.1186/s12911-023-02402-1.
[36]	WAHLSTRÖM A, SAYIN SI, MARSCHALL HU, et al. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism[J]. Cell Metab, 2016, 24( 1): 41- 50. DOI: 10.1016/j.cmet.2016.05.005.
[37]	NAMISAKI T, NOGUCHI R, MORIYA K, et al. Beneficial effects of combined ursodeoxycholic acid and angiotensin-II type 1 receptor blocker on hepatic fibrogenesis in a rat model of nonalcoholic steatohepatitis[J]. J Gastroenterol, 2016, 51( 2): 162- 172. DOI: 10.1007/s00535-015-1104-x.
[38]	MOON AN, BRIAND F, BREYNER N, et al. Improvement of NASH and liver fibrosis through modulation of the gut-liver axis by a novel intestinal FXR agonist[J]. Biomed Pharmacother, 2024, 173: 116331. DOI: 10.1016/j.biopha.2024.116331.
[39]	IWAMOTO J, HONDA A, MIYAZAKI T, et al. Western diet changes gut microbiota and ameliorates liver injury in a mouse model with human-like bile acid composition[J]. Hepatol Commun, 2021, 5( 12): 2052- 2067. DOI: 10.1002/hep4.1778.
[40]	LIU YH, CHEN KF, LI FY, et al. Probiotic Lactobacillus rhamnosus GG prevents liver fibrosis through inhibiting hepatic bile acid synthesis and enhancing bile acid excretion in mice[J]. Hepatology, 2020, 71( 6): 2050- 2066. DOI: 10.1002/hep.30975.
[41]	JANSSEN AWF, HOUBEN T, KATIRAEI S, et al. Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: A potential role for bile acids[J]. J Lipid Res, 2017, 58( 7): 1399- 1416. DOI: 10.1194/jlr.M075713.
[42]	XUE XY, WU JZ, DING MN, et al. Si-Wu-Tang ameliorates fibrotic liver injury via modulating intestinal microbiota and bile acid homeostasis[J]. Chin Med, 2021, 16( 1): 112. DOI: 10.1186/s13020-021-00524-0.
[43]	LIU F, SUN ZL, HU P, et al. Determining the protective effects of Yin-Chen-Hao Tang against acute liver injury induced by carbon tetrachloride using 16S rRNA gene sequencing and LC/MS-based metabolomics[J]. J Pharm Biomed Anal, 2019, 174: 567- 577. DOI: 10.1016/j.jpba.2019.06.028.
[44]	YU X, XUE ML, LIU Y, et al. Effect of nicotinamide riboside on lipid metabolism and gut microflora-bile acid axis in alcohol-exposed mice[J]. Food Sci Nutr, 2021, 9( 1): 429- 440. DOI: 10.1002/fsn3.2007.
[45]	LAGHI L, ROMÁN E, LAN QY, et al. A multistrain probiotic increases the serum glutamine/glutamate ratio in patients with cirrhosis: A metabolomic analysis[J]. Hepatol Commun, 2023, 7( 4): e0072. DOI: 10.1097/HC9.0000000000000072.
[46]	BASNET J, EISSA MA, YANES CARDOZO LL, et al. Impact of probiotics and prebiotics on gut microbiome and hormonal regulation[J]. Gastrointest Disord, 2024, 6( 4): 801- 815. DOI: 10.3390/gidisord6040056.
[47]	GUEVARA-GONZALÉZ J, GUEVARA-CAMPOS J, GONZÁLEZ L, et al. The effects of probiotics and prebiotics on gastrointestinal and behavioural symptoms in autism spectrum disorder[J]. Curr Rev Clin Exp Pharmacol, 2022, 17( 3): 166- 173. DOI: 10.2174/27724328166662108-05141257.
[48]	VITETTA L, COULSON S, LINNANE AW, et al. The gastrointestinal microbiome and musculoskeletal diseases: A beneficial role for probiotics and prebiotics[J]. Pathogens, 2013, 2( 4): 606- 626. DOI: 10.3390/path-ogens2040606.
[49]	van DORST JM, TAM RY, OOI CY. What do we know about the microbiome in cystic fibrosis? Is there a role for probiotics and prebiotics?[J]. Nutrients, 2022, 14( 3): 480. DOI: 10.3390/nu14030480.
[50]	HSU CL, SCHNABL B. The gut-liver axis and gut microbiota in health and liver disease[J]. Nat Rev Microbiol, 2023, 21( 11): 719- 733. DOI: 10.1038/s41579-023-00904-3.
[51]	YADEGAR A, BAR-YOSEPH H, MONAGHAN TM, et al. Fecal microbiota transplantation: Current challenges and future landscapes[J]. Clin Microbiol Rev, 2024, 37( 2): e00060-22. DOI: 10.1128/cmr.00060-22.
[52]	HE YF, WANG JC, WU FF, et al. Research progress in fecal microbiota transplantation in hepatobiliary and pancreatic surgery[J/OL]. Chin J Hepat Surg(Electronic Edition), 2025, 14( 4): 646- 653. DOI: 10.3877/cma.j.issn.2095-3232.2025.04.023. 何勇飞, 王继才, 吴芬芳, 等. 粪菌移植在肝胆胰外科领域研究进展[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14( 4): 646- 653. DOI: 10.3877/cma.j.issn.2095-3232.2025.04.023.
[53]	BAJAJ JS, KASSAM Z, FAGAN A, et al. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial[J]. Hepatology, 2017, 66( 6): 1727- 1738. DOI: 10.1002/hep.29306.
[54]	MEHTA R, KABRAWALA M, NANDWANI S, et al. Preliminary experience with single fecal microbiota transplant for treatment of recurrent overt hepatic encephalopathy-a case series[J]. Indian J Gastroenterol, 2018, 37( 6): 559- 562. DOI: 10.1007/s12664-018-0906-1.
[55]	OLMEDO M, REIGADAS E, VALERIO M, et al. Is it reasonable to perform Fecal Microbiota Transplantation for recurrent Clostridium difficile Infection in patients with liver cirrhosis?[J]. Rev Esp Quimioter, 2019, 32( 2): 205- 207.
[56]	GREEN JE, DAVIS JA, BERK M, et al. Efficacy and safety of fecal microbiota transplantation for the treatment of diseases other than Clostridium difficile infection: A systematic review and meta-analysis[J]. Gut Microbes, 2020, 12( 1): 1854640. DOI: 10.1080/19490976.2020.1854640.
[57]	FISCHER M, KAO DN, MEHTA SR, et al. Predictors of early failure after fecal microbiota transplantation for the therapy of Clostridium difficile infection: A multicenter study[J]. Am J Gastroenterol, 2016, 111( 7): 1024- 1031. DOI: 10.1038/ajg.2016.180.
[58]	IANIRO G, VALERIO L, MASUCCI L, et al. Predictors of failure after single faecal microbiota transplantation in patients with recurrent Clostridium difficile infection: Results from a 3-year, single-centre cohort study[J]. Clin Microbiol Infect, 2017, 23( 5): 337. DOI: 10.1016/j.cmi.2016.12.025.
[59]	QIU XX, CHENG SL, LIU YH, et al. Fecal microbiota transplantation for treatment of non-alcoholic fatty liver disease: Mechanism, clinical evidence, and prospect[J]. World J Gastroenterol, 2024, 30( 8): 833- 842. DOI: 10.3748/wjg.v30.i8.833.
[60]	XU ZC, LI MH, LYU DX, et al. Cinnamaldehyde activates AMPK/PGC-1α pathway via targeting GRK2 to ameliorate heart failure[J]. Phytomedicine, 2024, 133: 155894. DOI: 10.1016/j.phymed.2024.155894.
[61]	HAN RX, LI XY, GAO XF, et al. Cinnamaldehyde: Pharmacokinetics, anticancer properties and therapeutic potential(Review)[J]. Mol Med Rep, 2024, 30( 3): 163. DOI: 10.3892/mmr.2024.13287.
[62]	KHAN S, SANSONI S, DI COLA S, et al. A comparative study of dietary intake, nutritional status, and frailty in outpatients and inpatients with liver cirrhosis[J]. Nutrients, 2025, 17( 3): 580. DOI: 10.3390/nu17030580.
[63]	WEI T, JIN QG. Research trends and hotspots in exercise interventions for liver cirrhosis: A bibliometric analysis via CiteSpace[J]. Medicine, 2024, 103( 28): e38831. DOI: 10.1097/MD.00000000000-38831.
[64]	CIOVICESCU LM, CLICHICI SV, SIMEDREA RA, et al. Innovative prophylactic and therapeutic approaches in liver cirrhosis[J]. Physiol Int, 2024, 111( 1): 1- 18. DOI: 10.1556/2060.2024.00339.
[65]	KONSTANTIS G, POURZITAKI C, CHOURDAKIS M, et al. Efficacy of branched chain amino acids supplementation in liver cirrhosis: A systematic review and meta-analysis[J]. Clin Nutr, 2022, 41( 6): 1171- 1190. DOI: 10.1016/j.clnu.2022.03.027.
[66]	NISHIKAWA H, ENOMOTO H, NISHIGUCHI S, et al. Sarcopenic obesity in liver cirrhosis: Possible mechanism and clinical impact[J]. Int J Mol Sci, 2021, 22( 4): 1917. DOI: 10.3390/ijms22041917.

Relative Articles

Supplements(0)

Cited By

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Get Citation

PDF

XML

Article Metrics

Article views (36) PDF downloads(9)

Novel pathogenesis and intervention strategies for liver cirrhosis based on the gut microbiota-bile acid axis

DOI: 10.12449/JCH260330

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

Novel pathogenesis and intervention strategies for liver cirrhosis based on the gut microbiota-bile acid axis

DOI: 10.12449/JCH260330

Abstract

References

Proportional views

Catalog

通讯作者: 陈斌, bchen63@163.com

Article Metrics

Proportional views

Related

About Journal

Submission Guideline

Journal Online

Hepatobiliary College

Guidelines

Export File

Citation

Format

Content