Importantly, faecal microbiota transplantation (FMT) has shown considerable promise for rebalancing gut bacteria. In this vein, FMT interventions may positively impact DNA methylation, either directly or through the modulation of gut-derived metabolite influx. Despite this, the interplay between the gut microbiome and hepatic DNA methylation remains uncharacterised in humans.
By way of an FMT intervention and a multi-omics machine learning approach, this study aimed to examine interactions between gut microbiota composition, plasma metabolites, and altered liver DNA methylation in NAFLD.
Compared to autologous FMT, vegan allogenic donor FMT induced significant increases in gut microbiota, including Eubacterium siraeum and Blautia wexlerae. Increases in the former have been linked to high-density lipoprotein cholesterol levels in non-human primate models, while B. wexlerae has been identified as a potential anti-obesogenic probiotic. Allogenic FMT further altered plasma metabolites, including phenylacetylcarnitine, phenylacetylglutamine (PAG), and several choline-derived long-chain acylcholines responsible for fat and cholesterol transport from the liver. Importantly, PAG has been linked to hepatic dysfunction in NAFLD, and choline deficiency is a well-known driver of liver disease. Lastly, allogenic FMT modified DNA methylation profiles, including Threonyl-TRNA Synthetase 1 and Zinc finger protein 57, in patients with NAFLD. FMT can thus trigger alterations in metaorganismal pathways from the gut bacteria to the liver, supporting further therapeutic research into the gut-liver axis for NAFLD.