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

Jared D Hoffman,Lucille M Yanckello,Tyler C Hammond,Ishita Parikh,Scott D Mcculloch,Sydney Sun,Josh M Morganti,George Chlipala,Ai-Ling Lin,Stefan J Green,Florian Reichmann

doi:10.1371/journal.pone.0221828

Jared D Hoffman, Lucille M Yanckello + Show 9 more

Open Access

https://doi.org/10.1371/journal.pone.0221828

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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.

Highlights

Alzheimer’s disease (AD) is most common form of dementia with hallmarks of amyloid beta (Aβ) plaques and neurofibrillary tau tangles [1]
We found that the prebiotic inulin diet significantly altered gut microbiome diversity in E4FAD mice
By employing the Bray-Curtis dissimilarity metric followed by visualization of the data with an ordination plot, we observed that the fecal microbial community structures of E4FAD-Inulin mice were significantly different from that of the E4FAD-Control mice (ANOSIM R statistic = 0.877; p = 0.001; Fig 2B)

Summary

Introduction

Alzheimer’s disease (AD) is most common form of dementia with hallmarks of amyloid beta (Aβ) plaques and neurofibrillary tau tangles [1]. Research on AD has long been dominated by communications regarding the Aβ hypothesis and targeting Aβ accumulation in the brain through pharmacological therapies. This research strategy has failed to produce any FDA-approved disease-modifying therapeutics for Alzheimer’s disease despite over 900. Inulin alters gut microbiome and metabolism in APOE4 mice. All other relevant data are within the paper

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