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

Abstract Patients with cirrhosis have reduced gut-bacterial diversity and microbiota enriched with pathobionts. This enrichment, 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 small phase-I-trials, but its impact upon the disease process in cirrhosis is unexplored. We performed a randomised, placebo-controlled feasibility trial of jejunal FMT transplant in 32 advanced cirrhosis patients. The primary endpoint assessed safety, feasibility, and tolerability of FMT; secondary endpoints explored efficacy and mechanism. FMT was safe and well-tolerated with no serious adverse events. Deep-faecal-metagenomic sequencing confirmed FMT increased recipient species richness with significant donor engraftment. FMT reduced intestinal barrier damage and systemic inflammation. FMT decreased microbial-associated ammonia production and augmented ammonia excretion via anaerobic metabolism of L-aspartate to hippurateproviding proof of concept that FMT enhances ammonia metabolism, central in the pathogenesis of HEin cirrhosis.