Fellowship in support of Arjun Sinha: Role of the Gut Epithelium and Microbiota in Patients with Heart Failure

Patients with heart failure have increased levels of inflammation that are predictive of adverse outcomes. Thus, inflammation and heart failure are thought to mutually reinforce each other, creating a vicious cycle. Potential sources of increased inflammation have not been fully elucidated. The “leaky gut hypothesis” proposes that changes in the gut epithelium and microbiota lead to systemic inflammation and immune dysfunction in patients with heart failure. Epithelial dysfunction leads to translocation of bacterial products and toxins into the blood. Furthermore, metabolites generated by gut microbiota have systemic effects and modulate inflammation. Therefore, changes in the gut microbiota affects both gut epithelial function and the metabolites generated by these microbes. While a few studies have evaluated how individual components of the gut change with heart failure, there has not been a systematic longitudinal analysis of gut epithelial function, gut microbiota, and gut microbiota metabolites in patients with heart failure. We aim to characterize these changes that occur in the gut of heart failure patients and understand their longitudinal impact on cardiac function, inflammation, and immune dysfunction. This systems biology approach will help us understand the role of the gut in heart failure, leading to development of new diagnostic biomarkers and therapies.