Date of Award

Fall 2025

Document Type

Open Access Dissertation

Department

Biomedical Engineering

First Advisor

Jay Potts

Abstract

Heart failure (HF) is increasingly recognized as a multisystem disease often linked to gut dysbiosis; however, its specific effects on gut microbial composition remain poorly understood. This study examined long-term changes in the gut microbiome in a murine HF model induced by transverse aortic constriction (TAC) and evaluated the effects of NMEG-CGRP. TAC mimics pressure overload-induced cardiac dysfunction, replicating key features of HF. CGRP, a neuropeptide with vasodilatory and cardioprotective effects, shows potential as a therapy for HF but is limited by rapid degradation. A stabilized analog, NMEG-CGRP, was used to assess its impact on cardiac and gastrointestinal health. Mice were divided into four groups: SHAM, SHAM NMEG-CGRP, TAC, and TAC NMEG-CGRP, with fecal samples collected weekly. Microbial changes were analyzed via 16S rRNA sequencing, and cardiac structure was evaluated to explore links between microbiome shifts and remodeling. Diversity analyses revealed differences in microbial diversity across groups. For microbiome evaluation, SCFA-producing bacteria—commonly decreased in HF—were found at lower levels in the TAC group but increased in the TAC NMEG-CGRP group, suggesting partial recovery of SCFA-related microbes with treatment. NMEG-CGRP mitigated some microbial alterations induced by TAC. Correlations between microbial composition and cardiac metrics support a gut-heart axis modulated by both HF and vasodilatory treatment. These findings highlight the potential role of the gut microbiota in cardiac remodeling and HF progression, warranting further investigation into underlying mechanisms.

Rights

© 2025, Gleason

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