Targeting the Gut-Heart Axis Improves Cardiac Remodeling in a Clinical Scale Model of Cardiometabolic Syndrome
Florence M. Herisson, Gaston Cluzel, Maria Antonia Llopis-Grimalt, Aoife N. O’Donovan, Fatma Koç, Kavita Karnik, Ieva Laurie, Kirstie Canene‐Adams, R. Paul Ross, Catherine Stanton, Noel M. Caplice
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.