The Gut–Muscle Axis in Polycystic Ovary Syndrome: Proposed Mechanistic Roles of Intestinal Permeability, Bile Acid Signalling, and Skeletal Muscle Dysfunction

Polycystic ovary syndrome is a heterogeneous endocrine and metabolic disorder diagnosed when at least two of three features—chronic anovulation, hyperandrogenism, and polycystic ovarian morphology—are present, according to the Rotterdam criteria endorsed by the 2023 International Evidence-Based Guideline. Its metabolic burden extends well beyond reproduction. Insulin resistance, low-grade systemic inflammation, and central adiposity are common, and recent work links the composition of the gut microbiota and the integrity of the intestinal barrier to each of these features, the association between dysbiosis and the pathogenesis of the syndrome having been reviewed in detail. The same gut-related disturbances are now being connected to a second, less recognized consequence of the syndrome: impaired skeletal muscle health. In one cohort, an increased prevalence of sarcopenic obesity has been reported in PCOS despite the anabolic potential of androgen excess, and this review proposes that the two observations are mechanistically linked. Two candidate pathways connect the gut to muscle in PCOS. The first runs from increased intestinal permeability to circulating lipopolysaccharide, which activates Toll-like receptor 4 and a cascade of pro-inflammatory cytokines that blunt insulin signalling in skeletal myocytes. The second runs through bile acids: PCOS is characterized by a distinct circulating bile acid profile, currently described in a preprint that has not undergone peer review, while peer-reviewed profiling has confirmed altered circulating bile acid signatures and links to hyperandrogenism in women with PCOS. Signalling through the farnesoid X receptor and Takeda G protein-coupled receptor 5 has been shown to regulate muscle insulin sensitivity, mitochondrial oxidative capacity, and protein turnover in experimental systems, although direct demonstration in human PCOS muscle is lacking. Both pathways are predicted to converge on the IRS-1–PI3K–Akt–mTORC1 axis, the signalling hub through which muscle cells normally translate insulin into glucose uptake and protein synthesis. After reviewing the evidence for gut barrier dysfunction and skeletal muscle impairment in PCOS, we propose a dual-axis model linking intestinal permeability, bile acid signalling, and sarcopenic obesity. We then consider the therapeutic potential of interventions targeting the microbiota, bile acid receptors, inflammation, and muscle function, and outline the study designs that could test the model directly.