Characterization of the gut-liver- muscle axis in cirrhotic patients with sarcopenia

Background & Aim: Sarcopenia is frequent in cirrhosis and is associated with unfavourableoutcomes. The role of the gut-liver- muscleaxis in this setting has been poorly investigated. The aim of this study was to identify gut microbiota, metabolic and inflammatory signatures associated with sarcopenia in cirrhotic patients. Methods: Fifty cirrhotic patients assessed for the presence of sarcopenia by the quantificationof muscle mass and strength were compared with age-andsex-matchedcontrols. A multiomic analysis, including gut microbiota composition and metabolomics, serum myokines and systemic and intestinal inflammatory mediators, wasperformed. Results: The gut microbiota of sarcopenic cirrhotic patients was poor in bacteriaassociated with physical function (Methanobrevibacter, Prevotella and Akkermansia),and was enriched in Eggerthella, a gut microbial marker of frailty. Theabundance ofpotentially pathogenic bacteria, such as Klebsiella, was also increased, to the detriment of autochthonous ones. Sarcopenia was associated with elevated serum levelsof pro-inflammatorymediators and of fibroblast growth factor 21 (FGF21) in cirrhoticpatients. Gut microbiota metabolic pathways involved in amino acid, protein and branched-chainamino acid metabolism were up-regulated,in addition to ethanol,trimethylamine and dimethylamine production. Correlation networks and clusters of variables associated with sarcopenia were identified, including one centred onKlebsiella/ethanol/FGF21/Eggerthella/Prevotella. Conclusions: Alterations in the gut-liver-muscleaxis are associated with sarcopenia inpatients with cirrhosis. Detrimental but also compensatory functions are involved inthis complex network.