Project description: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.
Project description:Maternal secretor status is one of the determinants of human milk oligosaccharides (HMOs) composition, which in turn changes the gut microbiota composition of infants. To understand if this change in gut microbiota impacts immune cell composition, intestinal morphology and gene expression, day 21-old germ-free mice were transplanted with fecal microbiota from infants whose mothers were either secretors (SMM) or non-secretors (NSM) or from infants consuming dairy-based formula (MFM). For each group, one set of mice was supplemented with HMOs. HMO supplementation did not significantly impact the microbiota diversity however, SMM mice had higher abundance of genus Bacteroides, Bifidobacterium, and Blautia, whereas, in the NSM group, there were higher abundance of Akkermansia, Enterocloster, and Klebsiella. In MFM, gut microbiota was represented mainly by Parabacteroides, Ruminococcaceae_unclassified, and Clostrodium_sensu_stricto. In mesenteric lymph node, Foxp3+ T cells and innate lymphoid cells type 2 (ILC2) were increased in MFM mice supplemented with HMOs while in the spleen, they were increased in SMM+HMOs mice. Similarly, serum immunoglobulin A (IgA) was also elevated in MFM+HMOs group. Distinct global gene expression of the gut was observed in each microbiota group, which was enhanced with HMOs supplementation. Overall, our data shows that distinct infant gut microbiota due to maternal secretor status or consumption of dairy-based formula and HMO supplementation impacts immune cell composition, antibody response and intestinal gene expression in a mouse model.