Fecal microbiota transplantation mitigates cardiac remodeling and functional impairment in mice with chronic colitis

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestines accompanied by profound extra-intestinal manifestations. Although IBD shows a clear clinical association with cardiovascular derangements, whether and how chronic colitis impairs heart function remains unclear. To address this gap, we investigated the impact of chronic colitis on cardiac performance and the cardiac transcriptome using two mouse models: DSS-treated and <i>Il10^-/-</i> mice. Heart function was assessed by echocardiography and molecular characterization was performed using RNA-sequencing, RT-qPCR, and Western blot. Both models exhibited significant functional cardiac impairment, characterized by reduced ejection fraction and fractional shortening along with histologically evident increase in collagen deposition, inflammation, and myofibril reorganization. Molecular analyses revealed a pro-fibrotic cardiac. RNA-sequencing unveiled a shared upregulation of eicosanoid-associated and inflammatory genes (<i>Cyp2e1, Map3k6, Pck1, Cfd</i>) across both models, alongside model-specific alterations in pathways governing cAMP and cGMP signaling, arachidonic and linoleic acid metabolism, and immune cell responses. DSS colitis caused differential regulation of 232 cardiac genes, while <i>Il10^-/-</i> colitis yielded 105 dysregulated genes. Notably, reconstitution of a healthy balance of gut microbiota by therapeutic fecal microbiota transplantation (FMT), validated using qPCR, successfully rescued heart function and mitigated fibrosis in both models. However, <i>Il10^-/-</i> mice demonstrated relatively less cardiac recovery following FMT, highlighting IL-10's cardioprotective and anti-inflammatory contribution. Collectively, these findings provide evidence that chronic colitis impairs heart function, offer novel insights into colitis-induced cardiac remodeling, and suggest that FMT mitigates cardiac dysfunction by correcting gut dysbiosis, attenuating systemic inflammation, and re-establishing homeostasis along the gut-heart axis.