Gut-heart axis: Cardiac remodeling in mouse models of chronic colitis 3622

Abstract Description Background & Aims: Inflammatory bowel disease is associated with increased cardiovascular risks, yet the impact of chronic colitis on cardiac health remains unclear. This study examines molecular and functional cardiac changes in two mouse models of colitis. Methods Chronic colitis was induced in 6-week-old B6 mice using 2% dextran sodium sulfate (DSS) in 4 cycles of 7 days, interspersed with 2-week recovery intervals. Some DSS mice received fecal microbiota transplants (FMT) after each cycle. IL10-/- mice, which develop spontaneous colitis, underwent monthly FMT from 2 to 10 months of age. Cardiac function was assessed by echocardiography, and RNA sequencing (RNA-seq) profiled heart transcriptomes. Results Both models confirmed chronic colitis and cardiac dysfunction, evidenced by reduced ejection fraction and fractional shortening. FMT significantly alleviated colitis and improved cardiac function. RNA-seq revealed 232 and 105 dysregulated cardiac genes in DSS and IL10-/- mice, respectively; FMT rescued 3 and 67 genes. Several dysregulated genes, including Fos, Ctgf, and Il1b, were validated by RT-qPCR. Fibrotic proteins including COL1A1 and Fibronectin were markedly elevated in colitis but suppressed by FMT. β-catenin overexpression, linked to fibrosis, was also markedly mitigated by FMT. Conclusions Chronic colitis impairs cardiac function by promoting fibrosis, likely mediated through β-catenin activation. FMT shows therapeutic potential in mitigating these effects. Funding Sources This work was supported by NIH/NHLBI R01HL152683 and NIH/NIDDK R01DK135193. Topic Categories Cellular Adhesion, Migration, and Inflammation (CAM)