Defining the Causal Contribution of the Gut Microbiota to Cardiomyopathy Pathogenesis as a Basis for Developing Microbiome-targeted Therapies

Authors

Xu Shi, University of Nebraska-LincolnFollow

First Advisor

Amanda Ramer-Tait

Committee Members

Jennifer Auchtung, Jay Reddy, Yanbin Yin, Edward Deehan

Date of this Version

12-2025

Document Type

Thesis

Citation

A dissertation presented to the faculty of the Graduate College at the University of Nebraska in partial fulfillment of requirements for the degree of Doctor of Philosophy

Major: Food Science and Technology (Bioinformatics)

Under the supervision of Professor Amanda Ramer-Tait

Lincoln, Nebraska December 2025

Comments

Copyright 2025, Xu Shi. Used by permission

Abstract

Heart failure (HF) is a leading cause of morbidity and mortality worldwide, placing substantial clinical and economic burdens on society. Although advances in therapy have improved patient outcomes, the biological mechanisms that drive HF onset and progression remain incompletely understood. Increasing evidence suggests that the gut microbiota, the trillions of microorganisms residing in the gastrointestinal tract, plays a key role in some forms of heart disease, especially cardiovascular disease. Moreover, gut microbial dysbiosis has been associated with systemic inflammation, metabolic imbalance, and immune dysregulation, all of which contribute to the pathophysiology of HF. Cardiomyopathy, a primary disorder of the heart muscle, is a major precursor to HF and provides a tractable model for investigating how gut microbial communities may influence cardiac remodeling and functional decline. Yet, despite a growing recognition of the gut-heart axis, the causal contribution of the microbiota to the pathogenesis of cardiomyopathy remains poorly defined. The goal of this dissertation was to elucidate whether the gut microbiota contributes to cardiomyopathy and to identify potential avenues for therapeutic intervention. Our findings demonstrate that (1) alterations in gut microbiota composition were associated with disease severity during the progression of cardiomyopathy; (2) employing microbiome-targeted interventions that alter gut ecology influenced cardiomyopathy outcomes; and (3) the abundance of specific members of the gut microbiota correlate strongly with indicators of cardiomyopathy disease severity. By defining the microbial contributions to the pathogenesis of cardiomyopathy, this dissertation advances our understanding of the gut-heart connection and establishes a conceptual framework for microbiome-based strategies to prevent or mitigate HF. Collectively, these insights highlight the translational potential of targeting the gut microbiota as a novel avenue for maintaining cardiac health and managing chronic heart disease.

Advisor: Amanda Ramer-Tait