Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions

Abstract

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.