Alterations in intestinal microbiota diversity, composition, and function in patients with sarcopenia

Lin Kang,Taihao Wang,Dong Hao,Xuan Qu,Pengtao Li,Danyang Wang

doi:10.1038/s41598-021-84031-0

Abstract

16S rRNA sequencing of human fecal samples has been tremendously successful in identifying microbiome changes associated with both aging and disease. A number of studies have described microbial alterations corresponding to physical frailty and nursing home residence among aging individuals. A gut-muscle axis through which the microbiome influences skeletal muscle growth/function has been hypothesized. However, the microbiome has yet to be examined in sarcopenia. Here, we collected fecal samples of 60 healthy controls (CON) and 27 sarcopenic (Case)/possibly sarcopenic (preCase) individuals and analyzed the intestinal microbiota using 16S rRNA sequencing. We observed an overall reduction in microbial diversity in Case and preCase samples. The genera Lachnospira, Fusicantenibacter, Roseburia, Eubacterium, and Lachnoclostridium—known butyrate producers—were significantly less abundant in Case and preCase subjects while Lactobacillus was more abundant. Functional pathways underrepresented in Case subjects included numerous transporters and phenylalanine, tyrosine, and tryptophan biosynthesis suggesting that protein processing and nutrient transport may be impaired. In contrast, lipopolysaccharide biosynthesis was overrepresented in Case and PreCase subjects suggesting that sarcopenia is associated with a pro-inflammatory metagenome. These analyses demonstrate structural and functional alterations in the intestinal microbiota that may contribute to loss of skeletal muscle mass and function in sarcopenia.

Highlights

16S ribosomal RNA (rRNA) sequencing of human fecal samples has been tremendously successful in identifying microbiome changes associated with both aging and disease
Preclinical data has strengthened the association between gut dysbiosis and age-related physical frailty and performance decline and has led to the hypothesis that a gut-muscle axis exists through which the microbiome influences whole body lean mass, skeletal muscle mass, and physical functioning[21]
Underrepresented pathways in criteria for defining sarcopenia (Case) subjects include cytoskeletal proteins, transporters, ATP-binding cassette (ABC) transporters, and phenylalanine, tyrosine, and tryptophan biosynthesis. These results suggest that key metabolic pathways related to cellular energy production, protein processing, and nutrient transport are differentially regulated in the pathologic setting of sarcopenia

Summary

Introduction

16S rRNA sequencing of human fecal samples has been tremendously successful in identifying microbiome changes associated with both aging and disease. Preclinical data has strengthened the association between gut dysbiosis and age-related physical frailty and performance decline and has led to the hypothesis that a gut-muscle axis exists through which the microbiome influences whole body lean mass, skeletal muscle mass, and physical functioning[21] By this model, variation in the gut microbiota and gut metagenome alters key biological processes such as the inflammatory milieu (for example, by increased permeability of the gut epithelial barrier)[22], nutrient bioavailability[23], and lipid metabolism[24], and can contribute to age-related muscle decline. Human data is limited, a number of studies in animal models support this hypothesis In their pioneering work, Backhed et al demonstrated that germ-free mice colonized with fecal samples from their conventionally-raised counterparts display a significant loss in lean body mass – which includes skeletal muscle m ass[25]. Proposed mechanisms underlying the effect of these bacteria on skeletal muscle include inflammation-mediated epithelial permeability, circulation of bacterial toxins (i.e., lipopolysaccharide, LPS; indoxyl sulfate), and resultant insulin resistance and skeletal muscle atrophy[32]

Methods

Results

Conclusion