Dietary inulin alters the gut microbiome, enhances systemic metabolism and reduces neuroinflammation in an APOE4 mouse model

Abstract

The apolipoprotein ε4 allele ( APOE4 ) is the strongest genetic risk factor for Alzheimer’s disease (AD). APOE4 carriers develop systemic metabolic dysfunction decades before showing AD symptoms. Accumulating evidence shows that the metabolic dysfunction accelerates AD development, including exacerbated amyloid-beta (Aβ) retention, neuroinflammation and cognitive decline. Therefore, preserving metabolic function early on may be critical to reducing the risk for AD. Here, we show that inulin increases beneficial microbiota and decreases harmful microbiota in the feces of young, asymptomatic APOE4 transgenic (E4FAD) mice and enhances metabolism in the cecum, periphery and brain, as demonstrated by increases in the levels of SCFAs, tryptophan-derived metabolites, bile acids, glycolytic metabolites and scyllo-inositol. We show that inulin also reduces inflammatory gene expression in the hippocampus. This knowledge can be utilized to design early precision nutrition intervention strategies that use a prebiotic diet to enhance systemic metabolism and may be useful for reducing AD risk in asymptomatic APOE4 carriers.

The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication

“…Given that AD has a complex pathology and that therapies that effectively halt the disease progression are still lacking, recent studies have focused on environmental components and diet-based possible prevention strategies by using transgenic animal models (161,162). In this context, several studies have established the benefits of a healthy microbiome on slowing AD and the correlation of dysbiosis with disease progression (7, 138,163). Consistent with this notion, a study by Zhang and coworkers showed that the microbiota composition and diversity were perturbed and the level of SCFAs was reduced in AD mice, predicting alterations in more than 30 metabolic pathways, which may be associated with amyloid deposition and ultrastructural abnormalities in the APP/PS1 mouse model (25).…”

Bioregional Alterations in Gut Microbiome Contribute to the Plasma Metabolomic Changes in Pigs Fed with Inulin

“…Unique contributions of the gut microbiota at each site to overall host health are not yet fully clarified but are likely dependent on diet ingredients and overall health of the host [12]. The gut microbiome in combination with diet, with the subsequent translocation of microbial metabolites from the intestine to the bloodstream, is likely to play a pivotal role in influencing systemic metabolism [13][14][15]. Inulin-associated alterations in the composition of the gut microbiota are well documented.…”

Microbiota modulation as preventative and therapeutic approach in Alzheimer’s disease

“…Prebiotics are dietary supplements used as food source by the microflora that offer a health benefit to the host regulating gut microbiota composition. Inulin, a well-studied prebiotic compound, enhanced systemic metabolism and decreased hippocampus inflammatory gene expression modulating gut microbiome composition in E4FAD mice even before the development of Ab [170]. Treatment of APP/PS1 transgenic mice with fructooligosaccharides (FOS), commonly found in fruits and vegetables, changed microbiota composition and activated the GLP-1 pathway with consequent amelioration of cognitive deficits and pathological changes.…”