Metabolites of the gut microbiota may serve as precise diagnostic markers for sarcopenia in the elderly

Abstract

Sarcopenia, a disease recognized by the World Health Organization, has posed a great challenge to the world in the current aging society. The vital role of the gut microbiome through the gut-muscle axis in sarcopenia is increasingly recognized. However, the working mechanisms by which the gut microbiota functions have not been fully explored in the multi-omics field. Here, we designed a cross-sectional study that recruited patients (n = 32) with sarcopenia and healthy old adults (n = 31). Diagnosis of sarcopenia was based on the Asian Working Group for Sarcopenia (AWGS) in 2019 criteria. Muscle mass was represented by appendicular skeletal muscle mass measured by using direct segmental multi-frequency bioelectrical impedance and muscle strength was evaluated using the handgrip strength. The Short Physical Performance Battery, the 5-time Chair Stand Test, and the 4-metre Walk Test were used to assess physical performance. Shotgun metagenomic sequencing was used to profile the gut microbiome in order to identify its construction and function. Metabolome based on untargeted metabolomics was applied to describe the features and structure of fecal metabolites. In clinical indexes including triglycerides and high-density lipoprotein cholesterol, we noted a significant decrease in triglycerides (TG) and a significant increase in high-density lipoprotein cholesterol (HDL-C) in patients with sarcopenia. Appendicular skeletal muscle mass of patients with sarcopenia was lower than the health group. Based on intestinal metagenomic and fecal metabolomic profiles, we found that the gut microbiome and metabolome were disturbed in patients with sarcopenia, with significant decreases in bacteria such as Bifidobacterium longum, Bifidobacterium pseudocatenulatum, and Bifidobacterium adolescentis, as well as metabolites such as shikimic acid. Also, we plotted supervised classification models at the species level of gut bacteria (AUC = 70.83–88.33) and metabolites (AUC = 92.23–98.33) based on machine learning, respectively. Based on the gut-muscle axis network, a potential mechanism is proposed along the gut microbiome - key metabolites - clinical index, that Phascolarctobacterium faecium affects appendicular skeletal muscle mass, calf circumference, handgrip strength, and BMI via Shikimic acid metabolites. This study elucidates the potential mechanisms by which the gut microbiome influences the progress of sarcopenia through metabolites and provides a meaningful theoretical foundation for reference in the diagnosis and treatment of sarcopenia.

Metabolic signatures and risk of sarcopenia in suburb-dwelling older individuals by LC-MS–based untargeted metabonomics

“…Several integrated studies investigating the relationship between blood and fecal untargeted metabolomics and sarcopenia have been published. These studies involve untargeted profiling to discern trait-specific or shared metabolites linked with muscle mass and strength ( 8 ), comparing the plasma metabolome ( 9 , 10 ), as well as analyzing the differences in fecal metabolites ( 11 – 13 ). Blood metabolomics primarily reflects systemic metabolic changes and can capture metabolites related to muscle metabolism, hormonal regulation, and systemic inflammation, which are directly relevant to the pathophysiology of sarcopenia.…”