Microbes, metabolites and muscle: Is the gut–muscle axis a plausible therapeutic target in Duchenne muscular dystrophy?

Citations Over TimeTop 10% of 2023 papers

Abstract

Skeletal muscle is the largest metabolic organ making up ∼50% of body mass. Because skeletal muscle has both metabolic and endocrine properties, it can manipulate the microbial populations within the gut. In return, microbes exert considerable influence on skeletal muscle via numerous signalling pathways. Gut bacteria produce metabolites (i.e., short chain fatty acids, secondary bile acids and neurotransmitter substrates) that act as fuel sources and modulators of inflammation, influencing host muscle development, growth and maintenance. The reciprocal interactions between microbes, metabolites and muscle establish a bidirectional gut-muscle axis. The muscular dystrophies constitute a broad range of disorders with varying disabilities. In the profoundly debilitating monogenic disorder Duchenne muscular dystrophy (DMD), skeletal muscle undergoes a reduction in muscle regenerative capacity leading to progressive muscle wasting, resulting in fibrotic remodelling and adipose infiltration. The loss of respiratory muscle in DMD culminates in respiratory insufficiency and eventually premature death. The pathways contributing to aberrant muscle remodelling are potentially modulated by gut microbial metabolites, thus making them plausible targets for pre- and probiotic supplementation. Prednisone, the gold standard therapy for DMD, drives gut dysbiosis, inducing a pro-inflammatory phenotype and leaky gut barrier contributing to several of the well-known side effects associated with chronic glucocorticoid treatment. Several studies have observed that gut microbial supplementation or transplantation exerts positive effects on muscle, including mitigating the side effects of prednisone. There is growing evidence in support of the potential for an adjunctive microbiota-directed regimen designed to optimise gut-muscle axis signalling, which could alleviate muscle wasting in DMD.

Related Papers

• → Metagenomic and metabolomic analyses unveil dysbiosis of gut microbiota in chronic heart failure patients(2018)359 cited
• → Quercetin improves gut dysbiosis in antibiotic-treated mice(2020)121 cited
• → Traumatic Brain Injury Induces Gastrointestinal Dysfunction and Dysbiosis of Gut Microbiota Accompanied by Alterations of Bile Acid Profile(2021)86 cited
• → Gut dysbiosis correction contributes to the hepatoprotective effects ofThymus quinquecostatusCelak extract against alcohol through the gut–liver axis(2021)20 cited
• → Gut microbiota dysbiosis in rats with LPS-induced liver diseases affected by Aronia melanocarpa polyphenols(2023)1 cited