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Targeting the Gut-Heart Axis Improves Cardiac Remodeling in a Clinical Scale Model of Cardiometabolic Syndrome
Florence M Herisson1,2, Gaston L Cluzel1,2, Maria Antonia Llopis-Grimalt1,2
1Centre for Research in Vascular Biology, University College Cork, Cork, Ireland.
Insights
A poor diet and gut imbalance create a gut-heart axis (GHA) linked to heart failure. A synbiotic intervention improved gut barrier function, reducing inflammation and cardiac changes, suggesting GHA is a new therapeutic target.
Area of Science:
- Cardiovascular Medicine
- Gastroenterology
- Microbiome Research
Background:
- The gut-heart axis (GHA) links gut health to cardiovascular conditions like heart failure with preserved ejection fraction (HFpEF).
- Limited clinical models exist to study the complex interactions within the GHA.
- Poor diet and gut dysbiosis are implicated in GHA dysfunction and inflammation.
Purpose of the Study:
- To investigate the role of the gut-heart axis in HFpEF.
- To explore the impact of gut barrier dysfunction on systemic and cardiac inflammation.
- To evaluate the therapeutic potential of targeting the GHA.
Main Methods:
- Utilized a clinical scale model to assess gut barrier function, systemic inflammation, and cardiac structural changes.
- Examined the colocalization of inflammation with apoptosis and hypertrophy in cardiac tissues.
- Administered a synbiotic intervention to evaluate its effect on gut permeability and cardiac parameters.
Main Results:
- Demonstrated significant gut barrier function loss, systemic inflammation, and microvascular inflammation in the context of the GHA.
- Observed colocalization of inflammation with left atrial apoptosis and left ventricular hypertrophy.
- Synbiotic intervention successfully reduced gut epithelial permeability, leading to decreased systemic inflammation and cardiac structural alterations.
Conclusions:
- Gut barrier function is crucial in regulating the gut-heart axis and its impact on HFpEF.
- Targeting gut barrier integrity via interventions like synbiotics offers a novel therapeutic strategy for HFpEF.
- The GHA represents a promising new paradigm for managing heart failure.
Abstract:
Poor diet, gut dysbiosis, and systemic inflammation constitute a gut-heart axis (GHA) that may affect heart failure with preserved ejection fraction. Clinical scale models to interrogate this axis are limited. Here, we show the full extent of the GHA-gut barrier function loss, systemic and microvascular inflammation, and its colocalization with apoptosis (left atrium) and hypertrophy (left ventricle). Gut barrier function primacy in regulating the GHA is supported by a synbiotic intervention that shuts down gut epithelial permeability, markedly decreasing systemic inflammation and, remarkably, cardiac structural changes in left heart chambers. These data support a new paradigm for targeting heart failure with preserved ejection fraction via the GHA.
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