PROFIT Trial: FMT in cirrhosis. Faecal microbiota transplant restores intestinal barrier function and augments ammonia metabolism in patients with cirrhosis: a randomised single-blind placebo-controlled trial

Patients with liver cirrhosis have reduced gut bacterial diversity over-represented by pathobionts. This, coupled with increased gut permeability and bacterial translocation, increases susceptibility to infection and death. Faecal microbiota transplant [FMT] previously restored gut diversity and improved hepatic encephalopathy (HE) in 10 patients with cirrhosis. We performed a placebo-controlled randomised-controlled feasibility trial of FMT transplanted into the jejunum in 32 patients with advanced cirrhosis. The primary endpoint assessed safety, feasibility and tolerability of FMT. Secondary endpoints provided preliminary evidence of efficacy and mechanism. FMT was safe and well-tolerated with no serious adverse events. Deep metagenomic sequencing confirmed FMT increased recipient species richness with significant donor engraftment. FMT reduced intestinal barrier damage and systemic inflammation. FMT reduced microbial-associated ammonia production and augmented ammonia excretion via anaerobic metabolism of L-aspartate to hippurate providing proof of concept that FMT augments ammonia metabolism, central in the pathogenesis of HE, a debilitating complication of cirrhosis