Cerebral glucose homeostasis deregulation has a role in the pathogenesis and the progression of Alzheimer’s Disease (AD). Current therapiesdelay the decline in cognitive capabilities and reminiscence loss without definitively curing AD.
Recent studies have focussed on the role of the gut microbiota in disorders associated with the central nervous system, with special interest in the modulation of the gut-brain axis.
Using 3xTg-AD triple transgenic AD mouse model, we have demonstrated that the oral administration of a formulation of lactic acid bacteria and bifidobacteria (namely SLAB51) counteracts cognitive decline, reduces Aβ aggregates and brain damages and partially restores the impaired neuronal proteolysis. Improvement of cognitive function is supported by enriched gut content of antiinflammatory Short Chain Fatty Acids (SCFAs) and increased plasma concentrations of neuroprotective gut peptide hormones that play a role in modulating neuronal functions like learning and memory. In detail, probiotics oral administration influences energy metabolism and glycolysis-gluconeogenesis in AD mice, enhancing Glucagon Like Peptide-1 (GLP-1) and Glucose-dependent Insulinotropic Polypeptide (GIP) plasma concentrations. Probiotics oral administration improves glucose uptake in 3xTg-AD mice by restoring the brain expression levels of key glucose transporters (GLUT3, GLUT1) and insulin-like growth factor I receptor β (IGF-IR β), in accordance with the diminished phosphorylation of AMP-Activated Protein Kinase (AMPK) and protein-kinase B (Akt). In parallel, phosphorylated tau aggregates decrease in treated mice. Probiotics counteract the time-dependent increase of glycated haemoglobin and the accumulation of Advanced Glycation End-products (AGE) in AD mice, consistently with memory improvement. Collectively, our facts elucidate the mechanism via which intestine microbiota manipulation ameliorates impaired glucose metabolism in AD, ultimately delaying the disorder development.
Published Date: 2024-07-29; Received Date: 2020-07-28
