Gut-heart axis: cardiac remodeling and heart failure in the context of inflammatory bowel disease and dysbiosis

Abstract

Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are debilitating and complex chronic gastrointestinal disorders that affect not only the gut but also extraintestinal organs, including the heart. The gut-heart cross talk has garnered increasing attention in recent years; however, the molecular mechanisms underlying this complex interplay remain poorly understood. This review explores the gut-heart axis, focusing on how IBD disrupts gut microbiota homeostasis and promotes cardiac remodeling through systemic inflammation and various mediators, ultimately contributing to the onset or progression of heart failure. IBD compromises the integrity of the intestinal barrier, allowing microbial metabolites such as trimethylamine N-oxide and phenylacetylglutamine, along with inflammatory cytokines and microRNAs (miRNAs) (e.g., miR-155, miR-21, and let-7a), to enter the circulation and contribute to cardiac remodeling and heart failure. We identify dysfunction of nucleotide-binding oligomerization domain-containing protein 2 as a critical link between gut immunity and cardiovascular pathology. In addition, we discuss emerging microbiome-based therapeutic strategies, including fecal microbiota transplantation and IL-23 inhibitors, aimed at restoring gut homeostasis and mitigating cardiovascular risk. By integrating molecular mechanisms, clinical evidence, and therapeutic approaches, this review underscores the pivotal role of gut dysbiosis in cardiac dysfunction and offers new perspectives for managing cardiac dysfunction in patients with IBD.

Keywords: Crohn’s disease; gut microbiome; gut-heart axis; heart disease; ulcerative colitis.

Fig. 1. NOD2’s dual role in the gut-heart axis:

The left panel illustrates how NOD2 mutations impair bacterial recognition, leading to gut barrier dysfunction, systemic inflammation (via TNF-α, IL-1, IL-6, TMAO, PAGl translocation), and cardiac remodeling in IBD [,,–56]. The right panel shows NOD2’s direct effects in cardiac tissue. A mutated NOD2 receptor deprives the heart from valuable protective mechanisms against chronic stress (e.g. hypertension, heart failure). Together, these pathways link gut immunity to cardiac outcomes, with implications for heart failure in IBD patients [59].