Assessment of a novel functional food modulating the microbiota-inflammation-brain axis in patients with heart failure and/or /atrial fibrillation patients (the AMBROSIA study): Protocol for a randomized controlled trial

Background and aims: Atrial fibrillation (AF), heart failure (HF), and undernutrition represent a complex triad with major clinical and socioeconomic consequences in older adults, often predisposing to frailty. Undernutrition often remains underdiagnosed due to a reliance on weight-based measures and limited awareness of inflammation-related cachexia. The AMBROSIA study aims to fill these gaps by exploring the response of the microbiota-inflammation-brain axis to a targeted, fortified food product-based intervention, with comprehensive outcome assessments, alongside mechanistic/exploratory -omics analyses and gut microbiota (GM) functional profiling. Methods and results: This single-center, prospective, parallel-group randomized controlled trial aims to enroll 120 older adults with confirmed AF and/or HF. Participants will be randomized 1:1 into an intervention group (n = 60) or control group (n = 60). All participants receive individualized dietary counseling; the intervention group additionally consumes one AMBROSIA nutritional bar daily for six months. The bar contains hydrolyzed proteins, inulin, CoQ₁₀, and probiotics (L. rhamnosus IMC 501® and L. paracasei IMC 502®) in a flavonoid-rich chocolate matrix. Clinical, cognitive, and nutritional data, along with blood, saliva, urine, and stool samples, will be collected at baseline, 3, and 6 months. The primary endpoint is the change in skeletal muscle mass, physical function and frailty, while secondary endpoints include changes in nutritional status, inflammation, GM, metabolomics, and quality of life. Conclusion: By integrating cutting-edge omics tools and a multidimensional nutritional strategy, AMBROSIA aims to uncover mechanisms driving undernutrition and identify biomarkers to support personalized interventions for older patients with AF and HF.