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 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 gut microbiota using a dual approach: i) a dynamic gastrointestinal simulator (simgi^®) inoculated with feces 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 direct, host-independent assessment of microbiota responses, showing increased Bifidobacterium and Lactobacillus levels, alongside 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 increased butyrate levels. Fecal lipidomic and proteomic analyses indicated improved lipid digestion, increased secretory IgA, and modulation of host proteins linked to gut-brain homeostasis. Systemically, elevated levels of iron, folate, and vitamin B12 were also observed. For the first time, this study shows that supplements such as Fortasyn Connect can beneficially modulate the gut ecosystem and related immune-metabolic pathways in early AD, thereby targeting disease-relevant mechanisms through the gut-brain axis, in the context of aging.