Randomised double-blind placebo-controlled trial protocol to evaluate the therapeutic efficacy of lyophilised faecal microbiota capsules amended with next-generation beneficial bacteria in individuals with metabolic dysfunction-associated steatohepatitis

Background: The spectrum of metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent, affecting 30% of the world's population, with a significant risk of hepatic and cardiometabolic complications. Different stages of MASLD are accompanied by distinct gut microbial profiles, and several microbial components have been implicated in MASLD pathophysiology. Indeed, earlier studies demonstrated that hepatic necroinflammation was reduced in individuals with MASLD after allogenic faecal microbiota transplantation (FMT) from healthy donors on a vegan diet. Here, we further investigate the therapeutic potential of gut microbiome modulation using a syntrophic combination of next-generation beneficial bacteria with FMT in individuals with advanced MASLD.

Methods and analysis: This trial is a randomised, double-blind, placebo-controlled study investigating the therapeutic potential of lyophilised faecal microbiota capsules (LFMCs) in individuals with metabolic dysfunction-associated steatohepatitis. In this study, 48 participants will be randomised 1:1 to receive either healthy vegan donor LFMCs or placebo for 24 weeks. In addition, all participants will be supplemented with a set of next-generation beneficial bacteria, including Anaerobutyricum soehngenii, pasteurised Akkermansia muciniphila and Bifidobacterium animalis subsp. lactis, as well as fructo-oligosaccharides. A liver biopsy will be performed at baseline and at the end of the trial. In addition, participants will be assessed through MRI, FibroScan, blood tests, faecal samples and continuous glucose monitoring. The first participant was enrolled on 25 April 2023.

Ethics and dissemination: Ethical approval was obtained from the Medical Ethics Committee of the University Medical Centre of Amsterdam. The results of this study will be disseminated through peer-reviewed journals.

Trial registration number: The trial is registered on clinicaltrials.gov (NCT05821010).