The Gut-Muscle Axis in Older Subjects with Low Muscle Mass and Performance: A Proof of Concept Study Exploring Fecal Microbiota Composition and Function with Shotgun Metagenomics Sequencing.

Marcello Giuseppe Maggio,Andrea Ticinesi,Tiziana Meschi,Leonardo Mancabelli,Sara Tagliaferri,Antonio Nouvenne,Christian Milani,Fulvio Lauretani,Daniele Del Rio,Marco Ventura

doi:10.3390/ijms21238946

Abstract

The gut microbiota could influence the pathophysiology of age-related sarcopenia through multiple mechanisms implying modulation of chronic inflammation and anabolic resistance. The aim of this study was to compare the fecal microbiota composition and functionality, assessed by shotgun metagenomics sequencing, between two groups of elderly outpatients, differing only for the presence of primary sarcopenia. Five sarcopenic elderly subjects and twelve non-sarcopenic controls, classified according to lower limb function and bioimpedance-derived skeletal muscle index, provided a stool sample, which was analyzed with shotgun metagenomics approaches, to determine the overall microbiota composition, the representation of bacteria at the species level, and the prediction of bacterial genes involved in functional metabolic pathways. Sarcopenic subjects displayed different fecal microbiota compositions at the species level, with significant depletion of two species known for their metabolic capacity of producing short-chain fatty acids (SCFAs), Faecalibacterium prausnitzii and Roseburia inulinivorans, and of Alistipes shahii. Additionally, their fecal metagenome had different representation of genes belonging to 108 metabolic pathways, namely, depletion of genes involved in SCFA synthesis, carotenoid and isoflavone biotransformation, and amino acid interconversion. These results support the hypothesis of an association between microbiota and sarcopenia, indicating novel possible mediators, whose clinical relevance should be investigated in future studies.

Highlights

Sarcopenia, defined as the loss of skeletal muscle mass and function typical of aging occurring in the absence of any identifiable cause, represents a relevant health condition increasing the risk of disability and mortality [1]
Five sarcopenic elderly subjects and twelve non-sarcopenic controls, classifie according to lower limb function and bioimpedance-derived skeletal muscle index, provided a stool sample, which was analyzed with shotgun metagenomics approaches, to determine the overall microbiota composition, the representation of bacteria at the species level, and the prediction of bacterial genes involved in functional metabolic pathways
Sarcopenic subjects displayed different fecal microbiota compositions at the species level, with significant depletion of two species known for their metabolic capacity of producing short-chain fatty acids (SCFAs), Faecalibacterium prausnitzii and Roseburia inulinivorans, and of Alistipes shahii

Summary

Introduction

Sarcopenia, defined as the loss of skeletal muscle mass and function typical of aging occurring in the absence of any identifiable cause, represents a relevant health condition increasing the risk of disability and mortality [1]. The pathophysiology of this condition is not fully understood, but the presence of age-related chronic inflammation and anabolic resistance seem to play a major role, especially when combined with behavioral risk factors for muscle wasting such as inactivity and malnutrition [2,3]. Both conditions have been recently merged into a new entity, called physical frailty and sarcopenia (PF&S) [7]

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