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

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

doi:10.1371/journal.pone.0221828

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

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

Research output: Contribution to journal › Article › peer-review

83 Scopus citations

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.

Original language	English
Article number	e0221828
Journal	PLoS ONE
Volume	14
Issue number	8
DOIs	https://doi.org/10.1371/journal.pone.0221828
State	Published - Aug 1 2019

Bibliographical note

Publisher Copyright:
© 2019 Hoffman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding

This research was supported by NIH grants R01AG054459 (funded by NIA and ODS), R01AG062480, NIH/CTSA grant UL1TR000117, and American Federation for Aging Research Grant #A12474 to A-LL and NIH/NIA R21AG058006 to JMM, and NIH/NIDDK Training Grant T32DK007778 to JDH and LMY. The 7T ClinScan small animal MRI scanner of the UK was funded by the S10 NIH Shared Instrumentation Program Grant (1S10RR029541-01). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health. SDM is employed by Metabolon Inc.. Metabolon Inc. provided support in the form of salary for author SDM but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Funders	Funder number
Hartford Foundation/American Federation	12474
Metabolon Inc.
National Institutes of Health (NIH)
National Institute on Aging	R01AG054459, R21AG058006
National Institute on Aging
National Institute of Diabetes and Digestive and Kidney Diseases	1S10RR029541-01, T32DK007778
National Institute of Diabetes and Digestive and Kidney Diseases
Office of Dietary Supplements	R01AG062480
Office of Dietary Supplements
Georgia Clinical and Translational Science Alliance	UL1TR000117
Georgia Clinical and Translational Science Alliance

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title = "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{\textquoteright}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.",

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AU - McCulloch, Scott D.

AU - Parikh, Ishita

AU - Sun, Sydney

AU - Morganti, Josh M.

AU - Green, Stefan J.

AU - Lin, Ai Ling

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N2 - 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.

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

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