Microbiota Alterations in Alzheimer's Disease: Involvement of the Kynurenine Pathway and Inflammation

Neurotox Res. 2019 Aug;36(2):424-436. doi: 10.1007/s12640-019-00057-3. Epub 2019 May 14.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease considered the major cause of dementia in the elderly. The main pathophysiological features of the disease are neuronal loss (mainly cholinergic neurons), glutamatergic excitotoxicity, extracellular accumulation of amyloid beta, and intracellular neurofibrillary tangles. However, other pathophysiological features of the disease have emerged including neuroinflammation and dysregulation of the kynurenine pathway (KP). The intestinal microbiota is a large and diverse collection of microorganisms that play a crucial role in regulating host health. Recently, studies have highlighted that changes in intestinal microbiota contribute to brain dysfunction in various neurological diseases including AD. Studies suggest that microbiota compositions are altered in AD patients and animal models and that these changes may increase intestinal permeability and induce inflammation. Considering that microbiota can modulate the kynurenine pathway and in turn neuroinflammation, the gut microbiome may be a valuable target for the development of new disease-modifying therapies. The present review aims to link the interactions between AD, microbiota, and the KP.

Keywords: Alzheimer’s disease; Inflammation; Kynurenine pathway; Microbiota; Probiotics.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / microbiology
  • Alzheimer Disease / pathology
  • Animals
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Inflammation / metabolism
  • Inflammation / microbiology
  • Inflammation / pathology
  • Kynurenine / metabolism*
  • Oxidative Stress / physiology
  • Signal Transduction / physiology*

Substances

  • Kynurenine