Influence of Yoga-based cardiac rehabilitation on gut-microbiome diversity and Gut–Heart–Brain axis (YoGH-Biome) in heart failure: a study protocol

Heart failure (HF) is a chronic and progressive cardiovascular condition associated with significant morbidity, mortality and healthcare burden. Increasing evidence points to a critical role of gut dysbiosis and the gut-heart-brain axis in HF pathophysiology. Altered gut microbiota may influence systemic inflammation, neurohormonal activity and cardiac function through gut-derived metabolites such as trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs). Yoga-based cardiac rehabilitation (Yoga-CaRe) is a cost-effective intervention that has been shown to improve quality of life, exercise capacity and cardiovascular outcomes in cardiac patients. However, the mechanism underlying its benefits remains unclear. Furthermore, its effect on gut microbiota diversity and the downstream impact on the gut-heart-brain axis in HF remains largely unexplored. This study outlines a prospective, randomised, open-label, blinded-endpoint trial investigating the effects of a 12-week Yoga-CaRe intervention versus enhanced standard care in 60 HF patients with reduced ejection fraction. Participants will be randomly assigned in a 1:1 ratio to either the Yoga-CaRe or the control group. The Yoga-CaRe group will participate in 20 supervised yoga sessions, complemented by guided daily home practice, while the control group will receive enhanced standard care. The trial will assess changes in gut microbiota composition, levels of gut-derived metabolites (TMAO and SCFAs), inflammatory biomarkers (TNF-α and high-sensitivity C reactive protein), heart rate variability, 6 min walk test (6MWT) and echocardiography. Biological samples and clinical data will be analysed using integrated bioinformatics and statistical approaches to evaluate intervention efficacy and identify potential mechanistic pathways. The YoGH-Biome study has received ethical clearance from the Institutional Ethics Committee of the SDM College of Medical Sciences and Hospital, India (SDMIEC/2025/1073). It is registered with the Clinical Trials Registry of India. Study results will be disseminated via scientific publications, conferences and stakeholder forums to inform integrative strategies for HF management. Trial registration number: CTRI/2023/12/060757.