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Cross-sectional study reveals altered gut microbiota and medication risk factors for sarcopenia in oldest-old men, suggesting gut-muscle axis involvement in age-related muscle loss.
The sarcopenia burden is escalating in super-aged societies. The “gut-muscle axis” hypothesis suggests gut dysbiosis contributes to muscle wasting via inflammation and metabolic dysregulation, yet identifying consistent markers is complicated by heterogeneity. This study determined prevalence, risk factors, and microbiota signatures in a homogeneous cohort of community-dwelling men aged ≥ 75 receiving chronic disease management in Shanghai. We employed a cross-sectional design, enrolling 172 older men (mean age 82 ± 3 years). Sarcopenia was diagnosed using AWGS 2019 criteria. Comprehensive clinical data, including serological markers and medication history, were collected. Fecal samples from a subgroup ( n = 45) underwent 16 S rRNA sequencing. Clinical risk factors were identified using backward stepwise multivariate logistic regression with Bootstrap internal validation. Multivariate logistic regression and Linear Discriminant Analysis Effect Size (LEfSe) were used to identify independent factors. To mitigate potential overfitting and small-sample bias in the microbiota analysis, complementary differential abundance testing (e.g., ANCOM-BC) and exploratory penalized multivariable modeling (LASSO feature selection and Firth’s penalized regression) were strictly applied. Sarcopenia prevalence was 25.6%. The internally validated multivariate analysis identified five independent clinical risk factors: older age (OR = 1.146), lower BMI (OR = 0.671), CKD stages 3–5 (OR = 2.520), α-glucosidase inhibitors (AGIs) use (OR = 4.376), and lower LDH levels (OR = 0.983). Diabetes was not an independent risk factor. Microbiota analysis confirmed a robust depletion of SCFA-producing taxa. In the exploratory Firth’s penalized multivariable model guided by LASSO feature selection (adjusted for age and BMI), Citrobacter enrichment demonstrated a strong, marginally significant predictive trend for sarcopenia (OR = 1.388, p = 0.056). Sarcopenia in this managed cohort is associated with a complex interplay of metabolic aging, medication effects (AGIs), and specific dysbiosis. The exploratory identification of Citrobacter as a potential microbial marker provides preliminary insights into the “gut-muscle axis” and highlights a target requiring future longitudinal validation.
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Liu et al. (2026) studied this question.
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