Fibre supplementation alters the gastrointestinal microbiome, the microbial metabolites and indicators of neurodegeneration in a mouse model of Alzheimer´s disease

Abstract

Alzheimer´s disease is a neurodegenerative disease with high global prevalence and no cure available. It is known that the microbiota-gut-brain-axis plays a role in the pathogenesis, but the pathways are not fully understood yet. To elucidate the role of dietary fibre supplementation on this axis in a 5xFAD mouse model of Alzheimer´s disease, a feeding trial with an inulin supplement was conducted. At the start (Basis, n = 11) and after 7 weeks with (AD + F; n = 15) and without (AD; n = 15) supplementation, the mice were sacrificed and the following samples were taken: ingesta for 16 S rRNA sequencing and short-chain fatty acid (SCFA) analysis, and brain tissue for amyloid-beta staining and proteome analysis. The microbiota patterns in stomach, small intestine, caecum and colon differed between AD and AD + F. SCFA concentrations were significantly higher in group AD + F as compared to AD and Basis. In the AD mice, plaque load was significantly increased as compared to Basis, while a reduction in AD + F as compared to AD was observed. The brain proteome also differed between AD + F and AD, indicating a beneficial effect of the inulin supplementation, possibly mediated in part by microbial acetate. Since prebiotic substances like inulin are also part of human diets, this should be investigated further in the translational context.