Context-sensitive network analysis identifies food metabolites associated with Alzheimer\u2019s disease: an exploratory study

Yang Chen,Rong Xu

doi:10.1186/s12920-018-0459-2

Abstract

BackgroundDiet plays an important role in Alzheimer’s disease (AD) initiation, progression and outcomes. Previous studies have shown individual food-derived substances may have neuroprotective or neurotoxic effects. However, few works systematically investigate the role of food and food-derived metabolites on the development and progression of AD.MethodsIn this study, we systematically investigated 7569 metabolites and identified AD-associated food metabolites using a novel network-based approach. We constructed a context-sensitive network to integrate heterogeneous chemical and genetic data, and to model context-specific inter-relationships among foods, metabolites, human genes and AD.ResultsOur metabolite prioritization algorithm ranked 59 known AD-associated food metabolites within top 4.9%, which is significantly higher than random expectation. Interestingly, a few top-ranked food metabolites were specifically enriched in herbs and spices. Pathway enrichment analysis shows that these top-ranked herb-and-spice metabolites share many common pathways with AD, including the amyloid processing pathway, which is considered as a hallmark in AD-affected brains and has pathological roles in AD development.ConclusionsOur study represents the first unbiased systems approach to characterizing the effects of food and food-derived metabolites in AD pathogenesis. Our ranking approach prioritizes the known AD-associated food metabolites, and identifies interesting relationships between AD and the food group “herbs and spices”. Overall, our study provides intriguing evidence for the role of diet, as an important environmental factor, in AD etiology.

Highlights

Diet plays an important role in Alzheimer’s disease (AD) initiation, progression and outcomes
Our study consists of four steps (Fig. 2): first, we construct the GMF network using databases in Fig. 1; second, we prioritize AD-associated metabolites using a networkbased ranking algorithm with the input of AD-causing genes; third, we evaluate the metabolite ranking using the known disorder-metabolite associations provided by Human Metabolome Database (HMDB); and we investigate the common pathways shared by AD and top-ranked food metabolites to gain insights into how the metabolites affect AD
We first extract the three types of nodes for the network: the metabolite nodes are extracted from HMDB [16]; the gene nodes are obtained from The HUGO Gene Nomenclature Committee (HGNC) [30] and labeled by approved gene names

Summary

Introduction

Diet plays an important role in Alzheimer’s disease (AD) initiation, progression and outcomes. Previous studies have shown individual food-derived substances may have neuroprotective or neurotoxic effects. Few works systematically investigate the role of food and food-derived metabolites on the development and progression of AD. Diet plays an important role in the disease development [2]. A number of experimental studies have investigated individual foodderived substances, such as resveratrol [10], vitamin [11], and advanced glycation end products [12], and demonstrated their neuroprotective or neurotoxic effects. Systematic study of food metabolites and their associations with AD may offer insights into the disease-environment relationship and disease prevention, but currently remains unexplored

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