Deciphering the Gut-Muscle Axis: Mechanistic Links between Gut Microbiota and Muscle Disease

Sarcopenia in postmenopausal women has significant implications for health due to an elevated risk of osteoporosis, falls, fractures, and functional decline. Similarly, energy deficit in extreme exercise can contribute to muscle dysfunction in young women, particularly in the context of amenorrhoea. Emerging evidence suggests that intricate interplay between the gut microbiome, skeletal muscle, and oestrogen-responsive tissues can influence the severity of skeletal muscle dysfunction. For example, a reduction in microbial diversity in the gut may lead to lower levels of B-glucuronidase, which is necessary for the deconjugation of oestrogen into its active forms, thus reducing circulating oestrogens.

The project will therefore investigate the effects of dietary manipulation (spanning changes in short-chain fatty acids, calorific content, fat and fibre) on gut composition and muscle function in health and in response to oestrogen deficiency and the energy deficit observed in extreme exercise. Employing bioinformatics, shotgun metagenomics and RNAseq, the impact of dietary changes on gut composition and muscle function will be assessed using in vitro assays, murine models and a randomised controlled trial involving army personnel. This project promises not only to enhance our understanding of the complex mechanisms underlying muscle dysfunction but also hold significant implications for developing targeted interventions to combat sarcopenia and related muscle disease in postmenopausal women and in young women engaged in extreme exercise.