Gut Microbiota Modulation and Fecal Transplantation: An Overview on Innovative Strategies for Hepatic Encephalopathy Treatment

SIMPLE SUMMARY: Treatment of advanced liver disease and its complications continue to be a challenge due to the complexity of this illness. In recent years, the gut microbiome has been recognized to play a beneficial role in our health. Studies have shown that overgrowth of harmful organisms in the gut can contribute to worsened outcomes in liver disease. Fecal microbiota transplant (FMT) is an approved and effective treatment in other gastrointestinal conditions. FMT involves the administration of a solution of a fecal suspension from a healthy donor into the intestinal tract of a recipient. This has led researchers to attempt this treatment in liver disease. There have now been small clinical trials showing that FMT is safe and could be effective in improving outcomes in advanced liver disease. There remain several questions to be answered before FMT is implanted in clinical practice, including the best route to administer this treatment, how many doses are needed to achieve a therapeutic response, and how long we need to wait between treatments. In this review paper, we explore the role of the gut microbiome in the human body with emphasis on the gastrointestinal system, how it changes in liver disease, and how we can improve it with fecal microbiota transplant. ABSTRACT: Hepatic encephalopathy (HE) is a major complication of cirrhosis, which is associated with gut microbial composition and functional alterations. Current treatments largely focus on gut microbiota using lactulose, rifaximin and other agents. However, despite these treatments, patients with HE have a high rate of readmission, morbidity and cognitive impairment. Fecal microbiota transplant (FMT) involves introduction of a donor microbiota into a recipient and is currently mainly used for recurrent C. difficile infection (rCDI). The role of FMT in cirrhosis and HE is evolving. There have been two randomized clinical trials (RCT) and several case reports/series in cirrhosis. Both RCTs were safety-focused phase 1 trials. One involved pre-FMT antibiotics and FMT enema versus standard of care, while the other involved 15 FMT capsules versus placebo without pre-FMT antibiotics. There was evidence of safety in both trials and the FMT group demonstrated reduction in hospitalizations compared to the non-FMT group. Changes in microbial function centered around short-chain fatty acids, bile acids and brain function showed improvement in the FMT groups. Long-term follow-up demonstrated continued safety and reduction in the antibiotic-resistance gene carriage. However, larger trials of FMT in HE are needed that can refine the dose, duration and route of FMT administration.