An innovative functional cookie modulates the mucosa and myenteric plexus in the gut of 3xTG mouse model of Alzheimer’s disease

Neurodegenerative diseases are characterized by the gradual degeneration of the neuronal populations, leading to Alzheimer’s disease (AD) with the progressive onset of dementia, making this pathology one of the costliest and deadliest diseases of the current century. Patients with AD frequently exhibit reduced gut microbial diversity, suggesting a significant involvement of gut microbiota in influencing the pathogenesis and progression of AD. It has been proposed that gut dysbiosis, dysfunction of the intestinal epithelial barrier, and vascular deposition of amyloid-beta (Aβ) in the gut may precede the cerebral deposition of Aβ in a transgenic mouse model of AD.1 A hypocaloric cookie with prebiotic-rich ingredients (red lentils) coated with a multi-strain probiotic (SLAB51®) enriched chocolate2 was tested on 3xTg-AD mice, a murine model of AD, to evaluate the protective effects on the mucosa and ENS of the ileum and colon. 8-week-old 3xTg-AD gender-balanced mice were divided into five groups and organized for the supplementation of functional cookies. The morphology of the ileum and colonic wall, the mucus secretion, the intestinal barrier integrity, and neurodegeneration of the myenteric plexus were assessed with histochemical and immunochemical approaches. All the experimental animals showed a well-conserved morphology of the intestinal wall without fibrosis. The SLAB51®, administered alone or with the functional prebiotic enriched cookies, red lentils based appeared to be useful to reduce mucus secretion. The intestinal barrier integrity seems to be enhanced by the cookie supplementation, related to a decrease in inflammatory pathways. Moreover, in the ENS, gliosis was decreased in functional cookies supplemented mice without a clear modulation of enteric cholinergic and nitrergic neurons. This innovative symbiotic cookie could represent an innovative nutritional approach to prevent the onset of AD-related gut alterations and promote healthy aging. Funding: Next Generation EU - program “MUR-Fondo Promozione e Sviluppo - D.M. 737/2021.