Dysregulated bile acid synthesis and dysbiosis are implicated in Western diet-induced systemic inflammation, microglial activation, and reduced neuroplasticity

Prasant Kumar Jena, Lili Sheng, Jacopo Di Lucente, Lee-Way Jin, Izumi Maezawa, Yu-Jui Yvonne Wan

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The goal of this study was to identify the intrinsic links that explain the effect of a Western diet (WD) on cognitive dysfunction. Specific pathogen-free, wild-type mice were fed either a control diet (CD) or a high-fat, high-sucrose WD after weaning and were euthanized at 10mo of age to study the pathways that affect cognitive health. The results showed that long-term WD intake reduced hippocampal synaptic plasticity and the level of brainderived neurotrophic factor mRNA in the brain and isolated microglia. AWD also activated ERK1/2 and reduced postsynaptic density-95 in the brain, suggesting postsynaptic damage. Moreover, WD-fed mice had increased inflammatory signaling in the brain, ileum, liver, adipose tissue, and spleen, which was accompanied bymicroglia activation. In the brain, as well as in the digestive tract, a WD reduced signaling regulated by retinoic acid and bile acids (BAs),whose receptors form heterodimers to control metabolism and inflammation. Further more, a WD intake caused dysbiosis and dysregulated BA synthesis with reduced endogenous ligands for BA receptors, i.e., farnesoid X receptor and G-protein-coupled bile acid receptor in the liver and brain. Together, dysregulated BA synthesis and dysbiosis were accompanied by systemic inflammation, microglial activation, and reduced neuroplasticity induced by WD.

Original languageEnglish (US)
Pages (from-to)2866-2877
Number of pages12
JournalFASEB Journal
Volume32
Issue number5
DOIs
StatePublished - May 1 2018

Keywords

  • Alzheimer's disease
  • Cognition
  • FXR
  • Gut microbiota
  • TGR5

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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