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Updated: May 17, 2025
Murine Fecal Isolation and Microbiota Transplantation
Published on: May 26, 2023
Fecal microbiota transplantation mitigates cardiac remodeling and functional impairment in mice with chronic colitis
Insights
Fecal microbiota transplantation (FMT) improved heart function in inflammatory bowel disease (IBD) models by reducing cardiac fibrosis and inflammation. This highlights the gut-heart axis and the potential of microbiome therapies for IBD cardiovascular complications.
Area of Science:
- Cardiovascular Biology
- Gastroenterology
- Microbiome Research
Background:
- Inflammatory bowel disease (IBD) is linked to cardiovascular issues, but the underlying cardiac mechanisms are poorly understood.
- Chronic colitis models (DSS-induced and IL-10 deficient) were used to investigate colitis-induced cardiac remodeling and dysfunction.
Purpose of the Study:
- To elucidate the molecular mechanisms of cardiac dysfunction in inflammatory bowel disease (IBD).
- To assess the therapeutic potential of fecal microbiota transplantation (FMT) in mitigating colitis-associated cardiac pathology.
Main Methods:
- Two mouse models of chronic colitis (DSS-induced and IL-10 deficient).
- Echocardiography for cardiac function assessment.
- Molecular analyses including bulk RNA-sequencing, RT-qPCR, and Western blot.
- Fecal microbiota transplantation (FMT) as a therapeutic intervention.
Main Results:
- Both colitis models showed significant cardiac impairment, including fibrosis, inflammation, and altered gene expression (e.g., fibrosis markers, β-catenin reactivation).
- FMT treatment restored cardiac function, reduced fibrosis, and mitigated systemic inflammation in both models.
- Distinct molecular pathways were dysregulated in each model, with IL-10 deficiency highlighting its cardioprotective role.
Conclusions:
- Colitis induces cardiac remodeling and dysfunction through mechanisms involving systemic inflammation and gut dysbiosis.
- FMT shows promise in improving cardiovascular health in IBD by targeting the gut-heart axis.
- Further research into gut-heart interactions and microbiome-based therapies is crucial for managing IBD-related cardiovascular complications.
Background:
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder with significant extraintestinal manifestations, including cardiovascular derangements. However, the molecular mechanisms underlying the cardiac remodeling and dysfunction remain unclear.
Methods:
We investigated the effects of chronic colitis on the heart using two mouse models: DSS-induced colitis and Il10 -/- spontaneous colitis. Echocardiography was employed to assess heart function and molecular characterization was performed using bulk RNA-sequencing, RT-qPCR, and western blot.
Results:
Both models exhibited significant cardiac impairment, including reduced ejection fraction and fractional shortening as well as increased collagen deposition, inflammation, and myofibril reorganization. Molecular analyses revealed upregulation of fibrosis markers (i.e. COL1A1, COL3A1, Fibronectin) and β-catenin reactivation, indicating a pro-fibrotic cardiac environment. Each model yielded common upregulation of eicosanoid-associated and inflammatory genes ( Cyp2e1 , Map3k6 , Pck1 , Cfd ), and model-specific alterations in pathways regulating cAMP- and cGMP-signaling, arachidonic and linoleic acid metabolism, Cushing syndrome-related genes, and immune cell responses. DSS colitis caused differential regulation of 232 cardiac genes, while Il10 -/- colitis yielded 105 dysregulated genes, revealing distinct molecular pathways driving cardiac dysfunction. Importantly, therapeutic fecal microbiota transplantation (FMT) restored heart function in both models, characterized by reduced fibrosis markers and downregulated pro-inflammatory genes ( Lbp and Cdkn1a in Il10 -/- mice and Fos in DSS mice), while also mitigating intestinal inflammation. Post-FMT cardiac RNA-sequencing revealed significant gene expression changes, with three altered genes in DSS mice and 67 genes in Il10 -/- mice. Notably, Il10 -/- mice showed relatively less cardiac recovery following FMT, highlighting IL-10's cardioprotective and anti-inflammatory contribution.
Conclusions:
Our findings elucidate novel insights into colitis-induced cardiac remodeling and dysfunction and suggest that FMT mitigates cardiac dysfunction by attenuating systemic inflammation and correcting gut dysbiosis. This study underscores the need for further evaluation of gut-heart interactions and microbiome-based therapies to improve cardiovascular health in IBD patients.
