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Characterization of the gut‐liver‐muscle axis in cirrhotic patients with sarcopenia
Author(s) -
Ponziani Francesca Romana,
Picca Anna,
Marzetti Emanuele,
Calvani Riccardo,
Conta Giorgia,
Del Chierico Federica,
Capuani Giorgio,
Faccia Mariella,
Fianchi Francesca,
Funaro Barbara,
Josè CoelhoJunior Helio,
Petito Valentina,
Rinninella Emanuele,
Paroni Sterbini Francesco,
Reddel Sofia,
Vernocchi Pamela,
Cristina Mele Maria,
Miccheli Alfredo,
Putignani Lorenza,
Sanguinetti Maurizio,
Pompili Maurizio,
Gasbarrini Antonio
Publication year - 2021
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.14876
Subject(s) - sarcopenia , gut flora , cirrhosis , medicine , prevotella , akkermansia , metabolic syndrome , biology , gastroenterology , endocrinology , lactobacillus , bacteria , immunology , obesity , genetics
Background & Aim Sarcopenia is frequent in cirrhosis and is associated with unfavourable outcomes. The role of the gut‐liver‐muscle axis 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 quantification of muscle mass and strength were compared with age‐ and sex‐matched controls. A multiomic analysis, including gut microbiota composition and metabolomics, serum myokines and systemic and intestinal inflammatory mediators, was performed. Results The gut microbiota of sarcopenic cirrhotic patients was poor in bacteria associated with physical function ( Methanobrevibacter , Prevotella and Akkermansia ), and was enriched in Eggerthella , a gut microbial marker of frailty. The abundance of potentially pathogenic bacteria, such as Klebsiella , was also increased, to the detriment of autochthonous ones. Sarcopenia was associated with elevated serum levels of pro‐inflammatory mediators and of fibroblast growth factor 21 (FGF21) in cirrhotic patients. Gut microbiota metabolic pathways involved in amino acid, protein and branched‐chain amino 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 on Klebsiella /ethanol/FGF21/ Eggerthella / Prevotella . Conclusions Alterations in the gut‐liver‐muscle axis are associated with sarcopenia in patients with cirrhosis. Detrimental but also compensatory functions are involved in this complex network.