Proteomics of The multinutrient Fortasyn Connect influences gut microbiota and intestinal function in early Alzheimer´s disease

Nutritional supplementation is emerging as a promising strategy to support the clinical management of early Alzheimer’s disease (AD), partly through modulation of the intestinal microbiome via the microbiota–gut–brain axis. This study investigated the impact of Fortasyn Connect (Souvenaid®), a multinutrient formulation, on the gut microbiota using a dual approach: i) a dynamic gastrointestinal simulator (simgi®) inoculated with fecal samples from AD patients, and ii) an observational study involving early-stage AD patients (n = 22) receiving or not the supplement. The in vitro model provided a host-independent assessment of microbiota responses, revealing increased Bifidobacterium and Lactobacillus levels, along with enhanced short-chain fatty acid (SCFA) production. In patients, supplementation was associated with higher fecal abundance of Bifidobacterium and Christensenellaceae, reduced inflammatory markers (calprotectin and myeloperoxidase), and elevated butyrate levels. Fecal lipidomic and proteomic analyses indicated improved lipid digestion, increased secretory IgA, and modulation of host proteins related to gut–brain homeostasis. Systemically, higher circulating levels of iron, folate, and vitamin B12 were also observed. This study demonstrates that multinutrient supplementation such as Fortasyn Connect can beneficially modulate the gut ecosystem and immune–metabolic pathways in early AD, targeting disease-relevant mechanisms through the gut–brain axis in the context of aging.