Journal Article

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

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

2019

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Advertising executives / Aging / Alzheimer Disease - complications / Alzheimer Disease - pathology / Alzheimer Disease - physiopathology / Alzheimer's disease / Amyloid beta-Peptides - metabolism / Animals / Apolipoprotein E4 / Apolipoprotein E4 - genetics / Apolipoproteins / Bacteria - classification / Bile acids / Biology and Life Sciences / Body Weight - drug effects / Brain / Brain - drug effects / Brain - metabolism / Brain - pathology / Brain - physiopathology / Brain research / Carriers / Cecum / Cecum - drug effects / Cecum - metabolism / Chemokines / Cognition - drug effects / Cognitive ability / Control / Diabetes / Diet / Digestive system / Disease Models, Animal / Feeding Behavior / Gastrointestinal Microbiome - drug effects / Gene expression / Genes / Genetic engineering / Glucose metabolism / Glycolysis / Glycolysis - drug effects / Gut microbiota / Health risks / Humans / Inflammation / Inflammation - complications / Inflammation - drug therapy / Inflammation - microbiology / Inositol / Insulin / Intestinal microflora / Inulin / Inulin - pharmacology / Inulin - therapeutic use / Laboratory rats / Medicine and Health Sciences / Metabolic syndrome / Metabolism / Metabolites / Mice, Transgenic / Microbiomes / Microbiota / Microbiota (Symbiotic organisms) / Neurodegeneration / Neurosciences / Nutrition / Oxidative stress / Pharmacology / Research and Analysis Methods / Risk analysis / Risk factors / Signs and symptoms / Transgenic animals / Transgenic mice / Tryptophan / Type 2 diabetes