Exploring the Relationship Between Sleep Disturbances, Gut Microbiota, and Cognition in Patients with Heart Failure: A Cross-Sectional Study

Background and Objectives: Poor sleep quality and gut microbiota dysbiosis are independently associated with cognitive decline, yet their effects on cognition in heart failure (HF) patients remain unexamined. To assess the independent associations of sleep quality and gut microbiota diversity with cognition in patients with HF. Methods: This exploratory/pilot cross-sectional study enrolled adults with chronic stable HF from an outpatient cardiology clinic. Participants completed the Pittsburgh Sleep Quality Index (PSQI) and Montreal Cognitive Assessment (MoCA). Fecal samples were analyzed for gut microbiota composition, including Shannon diversity and Simpson indices. Multivariable linear regression analysis of MoCA scores with sleep quality and alpha diversity (Shannon index) as primary exposures, adjusted for age, sex, and left ventricular ejection fraction (LVEF) was conducted. Results: Of 59 enrolled patients (mean age 73.3 ± 10.8 years; 72.7% male; 86.4% White), 40 provided fecal samples. Analysis of microbiota data revealed a composition dominated by Bacillota (63.7%). In multivariable regressions, poor sleep quality was independently associated with lower MoCA scores (β = −3.01 to −3.88, p < 0.01). Similarly, Shannon diversity was also associated with lower MoCA (β = −3.45, p < 0.05). Beta-diversity analyses showed no consistent association between overall microbial community composition and cognition. No significant interactions between microbiota diversity and sleep variables were identified (all p > 0.20). Conclusions: Sleep quality and gut microbiota alpha diversity are independently associated with cognitive function in HF. Microbial pathways favoring short-chain fatty acid production align with better sleep, while lipopolysaccharide-related pathways associate with poorer sleep and cognition.