Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jan 27, 2024; 16(1): 17-32
Published online Jan 27, 2024. doi: 10.4254/wjh.v16.i1.17
Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions
Yash R Shah, Hassam Ali, Angad Tiwari, David Guevara-Lazo, Natalia Nombera-Aznaran, Bhanu Siva Mohan Pinnam, Manesh Kumar Gangwani, Harishankar Gopakumar, Amir H Sohail, SriLakshmiDevi Kanumilli, Ernesto Calderon-Martinez, Geetha Krishnamoorthy, Nimish Thakral, Dushyant Singh Dahiya
Yash R Shah, Geetha Krishnamoorthy, Department of Internal Medicine, Trinity Health Oakland/Wayne State University, Pontiac, MI 48341, United States
Hassam Ali, Division of Gastroenterology and Hepatology, East Carolina University/Brody School of Medicine, Greenville, NC 27858, United States
Angad Tiwari, Department of Internal Medicine, Maharani Laxmi Bai Medical College, Jhansi 284001, India
David Guevara-Lazo, Natalia Nombera-Aznaran, Faculty of Medicine, Universidad Peruana Cayetano Heredia, Lima 15102, Peru
Bhanu Siva Mohan Pinnam, Department of Internal Medicine, John H. Stroger Hospital of Cook County, Chicago, IL 60612, United States
Manesh Kumar Gangwani, Department of Internal Medicine, The University of Toledo, Toledo, OH 43606, United States
Harishankar Gopakumar, Department of Gastroenterology and Hepatology, University of Illinois College of Medicine at Peoria, Peoria, IL 61605, United States
Amir H Sohail, Department of Surgery, University of New Mexico, Albuquerque, NM 87106, United States
SriLakshmiDevi Kanumilli, Department of Internal Medicine, GSL Medical College, Rajamahendravaram 533296, India
Ernesto Calderon-Martinez, Department of Internal Medicine, Universidad Nacional Autonoma de Mexico, Ciudad De Mexico 04510, Mexico
Nimish Thakral, Department of Digestive Diseases and Nutrition, University of Kentucky, Lexington, KY 40536, United States
Dushyant Singh Dahiya, Division of Gastroenterology, Hepatology & Motility, The University of Kansas School of Medicine, Kansas City, KS 66160, United States
Author contributions: Shah YR, Ali H, Tiwari A, and Dahiya DS contributed to the conception and design; Shah YR, Krishnamoorthy G, and Dahiya DS contributed to the administrative support; Shah YR, Ali H, Nombera-Aznaran N, Pinnam BSM, Gangwani MK, Gopakumar H, Sohail AH, and Dahiya DS contributed to the provision, collection, and assembly of data; Shah YR, Ali H, Tiwari A, Guevara-Lazo D, Calderon-Martinez E, Nombera-Aznaran N, Pinnam BSM, Gangwani MK, Gopakumar H, Sohail AH, Kanumilli S, Thakral N, and Dahiya DS contributed to the review of literature and drafting the manuscript; Shah YR, Krishnamoorthy G, and Dahiya DS contributed to the revision of key components of the manuscript and final approval of manuscript; Shah YR, Ali H, Guevara-Lazo D, Calderon-Martinez E, Nombera-Aznaran N, Tiwari A, Pinnam BSM, Gangwani MK, Gopakumar H, Sohail AH, Kanumilli S, Krishnamoorthy G, Thakral N, and Dahiya DS are accountable for all aspects of the work.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Dushyant Singh Dahiya, MD, Doctor, Division of Gastroenterology, Hepatology & Motility, The University of Kansas School of Medicine, No. 2000 Olathe Blvd, Kansas City, KS 66160, United States.
Received: September 16, 2023
Peer-review started: September 16, 2023
First decision: November 22, 2023
Revised: December 2, 2023
Accepted: January 3, 2024
Article in press: January 3, 2024
Published online: January 27, 2024

Fecal microbiota transplantation (FMT) offers a potential treatment avenue for hepatic encephalopathy (HE) by leveraging beneficial bacterial displacement to restore a balanced gut microbiome. The prevalence of HE varies with liver disease severity and comorbidities. HE pathogenesis involves ammonia toxicity, gut-brain communication disruption, and inflammation. FMT aims to restore gut microbiota balance, addressing these factors. FMT's efficacy has been explored in various conditions, including HE. Studies suggest that FMT can modulate gut microbiota, reduce ammonia levels, and alleviate inflammation. FMT has shown promise in alcohol-associated, hepatitis B and C-associated, and non-alcoholic fatty liver disease. Benefits include improved liver function, cognitive function, and the slowing of disease progression. However, larger, controlled studies are needed to validate its effectiveness in these contexts. Studies have shown cognitive improvements through FMT, with potential benefits in cirrhotic patients. Notably, trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care. Although evidence is promising, challenges remain: Limited patient numbers, varied dosages, administration routes, and donor profiles. Further large-scale, controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy. While FMT holds potential for HE management, ongoing research is needed to address these challenges, optimize protocols, and expand its availability as a therapeutic option for diverse hepatic conditions.

Keywords: Hepatic encephalopathy, Fecal microbiota transplant, Cognitive impairment, Liver cirrhosis, Chronic liver disease

Core Tip: Hepatic encephalopathy (HE) is a reversible neurocognitive dysfunction and a frequent complication in patients with chronic liver disease. HE results from synergistic interaction between various mechanisms like increased ammonia production, systemic inflammation, disruption of the blood-brain barrier, and impairment of neurotransmission, leading to altered gut-brain-liver axis. Lactulose and rifaximin are the current mainstays of management of HE as they are known to decrease ammonia production. Fecal microbiota transplant is being studied as a potential microbiome targeted therapy that can improve the symptoms of HE by decreasing ammonia production, decreasing systemic inflammation, and improving intestinal barrier function.