Francesca Romana Ponziani1, Anna Picca2,3, Emanuele Marzetti2, Riccardo Calvani2,3, Giorgia Conta4, Federica Del Chierico5, Giorgio Capuani4,5,6, Mariella Faccia1, Francesca Fianchi1, Barbara Funaro1, Helio Josè Coelho-Junior2, Valentina Petito1, Emanuele Rinninella7, Francesco Paroni Sterbini8, Sofia Reddel5, Pamela Vernocchi5, Maria Cristina Mele9, Alfredo Miccheli6,7,8,9,10, Lorenza Putignani11, Maurizio Sanguinetti8, Maurizio Pompili1, Antonio Gasbarrini1. 1. Internal Medicine and Gastroenterology - Liver Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. 2. Department of Geriatrics, Neuroscience and Orthopedics, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. 3. Aging Research Center, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University, Stockholm, Sweden. 4. Department of Chemistry, Sapienza University of Rome, Rome, Italy. 5. Area of Genetics and Rare Diseases, Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy. 6. NMR-based Metabolomics Laboratory, Sapienza University of Rome, Rome, Italy. 7. Clinical Nutrition, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. 8. Microbiology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. 9. Advanced Nutrition in Oncology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy. 10. Department of Environmental Biology, Sapienza University of Rome, Rome, Italy. 11. Department of Laboratories, Unit of Parasitology and Area of Genetics and Rare Diseases, Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Abstract
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.
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 cirrhoticpatients 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.
Authors: Roman Maslennikov; Vladimir Ivashkin; Aliya Alieva; Elena Poluektova; Anna Kudryavtseva; George Krasnov; Maria Zharkova; Yuri Zharikov Journal: World J Hepatol Date: 2022-06-27