Haussinger D, Dhiman RK, Felipo V, Gorg B, Jalan R, Kircheis G, et al. Hepatic encephalopathy. Nat Rev Dis Primers. 2022;8(1):43. https://doi.org/10.1038/s41572-022-00366-6.
He X, Hu M, Xu Y, Xia F, Tan Y, Wang Y, et al. The gut-brain axis underlying hepatic encephalopathy in liver cirrhosis. Nat Med. 2025;31(2):627–38. https://doi.org/10.1038/s41591-024-03405-9.
Article PubMed CAS Google Scholar
Villanueva C, Tripathi D, Bosch J. Preventing the progression of cirrhosis to decompensation and death. Nat Rev Gastroenterol Hepatol. 2025;22(4):265–80. https://doi.org/10.1038/s41575-024-01031-x.
Kronsten VT, Paintsil EK, Rodrigues S, Seager MJ, Bernal W, Shawcross DL. Hepatic Encephalopathy: When Lactulose and Rifaximin Are Not Working. Gastroenterology. 2025;168(6):1076-1084.e1. https://doi.org/10.1053/j.gastro.2025.01.010.
Article PubMed CAS Google Scholar
Tilg H, Adolph TE, Trauner M. Gut-liver axis: pathophysiological concepts and clinical implications. Cell Metab. 2022;34(11):1700–18. https://doi.org/10.1016/j.cmet.2022.09.017.
Article PubMed CAS Google Scholar
Odenwald MA, Lin H, Lehmann C, Dylla NP, Cole CG, Mostad JD, et al. Bifidobacteria metabolize lactulose to optimize gut metabolites and prevent systemic infection in patients with liver disease. Nat Microbiol. 2023;8(11):2033–49. https://doi.org/10.1038/s41564-023-01493-w.
Article PubMed PubMed Central CAS Google Scholar
Desplats V, Haudebourg L, Verger N, Assaraf J, Mouri S, Bouzbib C, et al. Acute encephalopathy without hyperammonemia has a different presentation than overt HE and displays a similarly severe prognosis. Hepatology. 2025. https://doi.org/10.1097/hep.0000000000001252.
Gomez-Hurtado I, Such J, Frances R. Microbiome and bacterial translocation in cirrhosis. Gastroenterol Hepatol. 2016;39(10):687–96. https://doi.org/10.1016/j.gastrohep.2015.10.013.
Li S, Xu Z, Diao H, Zhou A, Tu D, Wang S, et al. Gut microbiome alterations and hepatic encephalopathy post-TIPS in liver cirrhosis patients. J Transl Med. 2025;23(1):745. https://doi.org/10.1186/s12967-025-06774-y.
Article PubMed PubMed Central CAS Google Scholar
Wu JL, Chen JW, Huang MS, Deng XY, Deng JJ, Lau TY, et al. The causal effect of gut microbiota on hepatic encephalopathy: a Mendelian randomization analysis. BMC Med Genomics. 2024;17(1):216. https://doi.org/10.1186/s12920-024-01939-y.
Article PubMed PubMed Central Google Scholar
Gao J, Nie R, Chang H, Yang W, Ren Q. A meta-analysis of microbiome therapies for hepatic encephalopathy. Eur J Gastroenterol Hepatol. 2023;35(9):927–37. https://doi.org/10.1097/meg.0000000000002596.
Article PubMed CAS Google Scholar
Yang Z, Liu S, Wei F, Hu J. The effects of Qingchang Ligan formula on hepatic encephalopathy in mouse model: results from gut microbiome-metabolomics analysis. Front Cell Infect Microbiol. 2024;14:1381209. https://doi.org/10.3389/fcimb.2024.1381209.
Article PubMed PubMed Central CAS Google Scholar
Mancini A, Campagna F, Amodio P, Tuohy KM. Gut: liver : brain axis: the microbial challenge in the hepatic encephalopathy. Food Funct. 2018;9(3):1373–88. https://doi.org/10.1039/c7fo01528c.
Article PubMed CAS Google Scholar
Jinato T, Sikaroodi M, Fagan A, Sterling RK, Lee H, Puri P, et al. Alterations in gut virome are associated with cognitive function and minimal hepatic encephalopathy cross-sectionally and longitudinally in cirrhosis. Gut Microbes. 2023;15(2):2288168. https://doi.org/10.1080/19490976.2023.2288168.
Article PubMed PubMed Central CAS Google Scholar
Lombardi M, Troisi J, Motta BM, Torre P, Masarone M, Persico M. Gut-liver axis dysregulation in portal hypertension: emerging frontiers. Nutrients. 2024. https://doi.org/10.3390/nu16071025.
Article PubMed PubMed Central Google Scholar
Smokovski I, Steinle N, Behnke A, Bhaskar SMM, Grech G, Richter K, et al. Digital biomarkers: 3PM approach revolutionizing chronic disease management - EPMA 2024 position. EPMA J. 2024;15(2):149–62. https://doi.org/10.1007/s13167-024-00364-6.
Article PubMed PubMed Central Google Scholar
Skladany L, Kubanek N, Adamcova Selcanova S, Zilincanova D, Havaj D, Sulejova K, et al. 3PM-guided innovation in treatments of severe alcohol-associated hepatitis utilizing fecal microbiota transplantation. EPMA J. 2024;15(4):677–92. https://doi.org/10.1007/s13167-024-00381-5.
Article PubMed PubMed Central Google Scholar
Liu Y, Hu Y, Ma B, Wang Z, Wei B. Gut microbiota and exercise: probiotics to modify the composition and roles of the gut microbiota in the context of 3P medicine. Microb Ecol. 2025;88(1):38. https://doi.org/10.1007/s00248-025-02529-w.
Article PubMed PubMed Central Google Scholar
Wang S, Zhang R, Guo P, Yang H, Liu Y, Zhu H. Association of prebiotic/probiotic intake with MASLD: evidence from NHANES and randomized controlled trials in the context of prediction, prevention, and a personalized medicine framework. EPMA J. 2025;16(1):183–97. https://doi.org/10.1007/s13167-025-00398-4.
Sharma BC, Singh J. Probiotics in management of hepatic encephalopathy. Metab Brain Dis. 2016;31(6):1295–301. https://doi.org/10.1007/s11011-016-9826-x.
Bajaj JS, O’Leary JG, Jakab SS, Fagan A, Sikaroodi M, Gillevet PM. Gut microbiome profiles to exclude the diagnosis of hepatic encephalopathy in patients with cirrhosis. Gut Microbes. 2024;16(1):2392880. https://doi.org/10.1080/19490976.2024.2392880.
Article PubMed PubMed Central CAS Google Scholar
Shamsaddini A, Gillevet PM, Acharya C, Fagan A, Gavis E, Sikaroodi M, et al. Impact of antibiotic resistance genes in gut microbiome of patients with cirrhosis. Gastroenterology. 2021;161(2):508-521.e7. https://doi.org/10.1053/j.gastro.2021.04.013.
Article PubMed CAS Google Scholar
Shukla S, Shukla A, Mehboob S, Guha S. Meta-analysis: the effects of gut flora modulation using prebiotics, probiotics and synbiotics on minimal hepatic encephalopathy. Aliment Pharmacol Ther. 2011;33(6):662–71. https://doi.org/10.1111/j.1365-2036.2010.04574.x.
Article PubMed CAS Google Scholar
Rivera-Flores R, Moran-Villota S, Cervantes-Barragan L, Lopez-Macias C, Uribe M. Manipulation of microbiota with probiotics as an alternative for treatment of hepatic encephalopathy. Nutrition. 2020;73:110693. https://doi.org/10.1016/j.nut.2019.110693.
Xin Z, Wang Z, Chu M. Insights into intestinal flora in metabolic dysfunction-associated steatotic liver disease. FASEB J. 2025;39(16):e70932. https://doi.org/10.1096/fj.202403293RR.
Article PubMed CAS Google Scholar
Patel VC, Lee S, McPhail MJW, Da Silva K, Guilly S, Zamalloa A, et al. Rifaximin-α reduces gut-derived inflammation and mucin degradation in cirrhosis and encephalopathy: RIFSYS randomised controlled trial. J Hepatol. 2022;76(2):332–42. https://doi.org/10.1016/j.jhep.2021.09.010.
Article PubMed CAS Google Scholar
Kronsten VT, Tranah TH, Pariante C, Shawcross DL. Gut-derived systemic inflammation as a driver of depression in chronic liver disease. J Hepatol. 2022;76(3):665–80. https://doi.org/10.1016/j.jhep.2021.11.008.
Article PubMed CAS Google Scholar
Diaz LA, Winder GS, Leggio L, Bajaj JS, Bataller R, Arab JP. New insights into the molecular basis of alcohol abstinence and relapse in alcohol-associated liver disease. Hepatology. 2025;82(1):254–71. https://doi.org/10.1097/hep.0000000000000645.
Comments (0)