Understanding the gut microbiota and sarcopenia: a systematic review

Abstract

Background: Gut microbiota dysbiosis and sarcopenia commonly occur in the elderly. Although the concept of the gut-muscle axis has been raised, the casual relationship is still unclear. This systematic review analyses the current evidence of gut microbiota effects on muscle/sarcopenia.

Methods: A systematic review was performed in PubMed, Embase, Web of Science, and The Cochrane Library databases using the keywords (microbiota* OR microbiome*) AND (sarcopen* OR muscle). Studies reporting the alterations of gut microbiota and muscle/physical performance were analysed.

Results: A total of 26 pre-clinical and 10 clinical studies were included. For animal studies, three revealed age-related changes and relationships between gut microbiota and muscle. Three studies focused on muscle characteristics of germ-free mice. Seventy-five per cent of eight faecal microbiota transplantation studies showed that the recipient mice successfully replicated the muscle phenotype of donors. There were positive effects on muscle from seven probiotics, two prebiotics, and short-chain fatty acids (SCFAs). Ten studies investigated on other dietary supplements, antibiotics, exercise, and food withdrawal that affected both muscle and gut microbiota. Twelve studies explored the potential mechanisms of the gut-muscle axis. For clinical studies, 6 studies recruited 676 elderly people (72.8 ± 5.6 years, 57.8% female), while 4 studies focused on 244 young adults (29.7 ± 7.8 years, 55.4% female). The associations of gut microbiota and muscle had been shown in four observational studies. Probiotics, prebiotics, synbiotics, fermented milk, caloric restriction, and exercise in six studies displayed inconsistent effects on muscle mass, function, and gut microbiota.

Conclusions: Altering the gut microbiota through bacteria depletion, faecal transplantation, and various supplements was shown to directly affect muscle phenotypes. Probiotics, prebiotics, SCFAs, and bacterial products are potential novel therapies to enhance muscle mass and physical performance. Lactobacillus and Bifidobacterium strains restored age-related muscle loss. Potential mechanisms of microbiome modulating muscle mainly include protein, energy, lipid, and glucose metabolism, inflammation level, neuromuscular junction, and mitochondrial function. The role of the gut microbiota in the development of muscle loss during aging is a crucial area that requires further studies for translation to patients.

Keywords: Aging; Function; Gut microbiota; Gut-muscle axis; Muscle; Sarcopenia.

Figure 1

Study search and selection process.

Figure 2

The molecular signalling pathways of gut microbiota and skeletal muscle: the noxious bacterial metabolites (indoxyl sulfate and LPS) and absence of gut microbiota (black) induced muscle atrophy., , , , , , Indoxyl sulfate and LPS caused muscle atrophy and inflammation by activating the PI3K/AKT, NF‐κB, and MAPKs (p38, JNK, ERK) signalling pathways to up‐regulate Atrogin‐1/MAFbx and MuRF1 genes encoding E3 ubiquitin ligases, and inflammatory cytokines. AMPK–FoxO3–Atrogin‐1/MuRF1 cascade and BCAAs catabolism were activated in the bacteria depletion condition. The expressions of IGF1, myogenin, and MyoD were reduced, and myostatin was increased. NMJ function and mitochondrial function were widely impaired. Supplements with probiotics, SCFAs, or germ‐free transplanted models showed (red) the suppression of GR and excessive AMPK activation, attenuated inflammation levels, mitochondrial and NMJ function repair, as well as increased the expressions of muscle growth‐related genes (IGF1, myogenin, SIK1) to maintain muscle mass and functions., , , For abbreviations of the main text, please see Table S3.