Targeting the Gut-Heart Axis Improves Cardiac Remodeling in a Clinical Scale Model of Cardiometabolic Syndrome

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.