Probiotics ameliorate intestinal pathophysiology in a mouse model of Alzheimer's disease

Neurobiol Aging. 2020 Aug;92:114-134. doi: 10.1016/j.neurobiolaging.2020.04.009. Epub 2020 Apr 18.

Abstract

Evidence suggests that changes in intestinal microbiota may affect the central nervous system. However, it is unclear whether alteration of intestinal microbiota affects progression of Alzheimer's disease (AD). To understand this, wild-type control (C57BL/6) mice were compared with the AppNL-G-F model of disease. We used probiotic supplementation to manipulate the gut microbiota. Fecal samples were collected for microbiota profiling. To study brain and intestinal inflammation, biochemical and histological analyses were performed. Altered metabolic pathways were examined by quantifying eicosanoid and bile acid profiles in the brain and serum using ultraperformance liquid chromatography-tandem mass spectrometry. We observed that brain pathology was associated with intestinal dysbiosis and increased intestinal inflammation and leakiness in AppNL-G-F mice. Probiotic supplementation significantly decreased intestinal inflammation and gut permeability with minimal effect on amyloid-β, cytokine, or gliosis levels in the brain. Concentrations of several bile acids and prostaglandins were altered in the serum and brain because of AD or probiotic supplementation. Our study characterizes intestinal dysfunction in an AD mouse model and the potential of probiotic intervention to ameliorate this condition.

Keywords: Alzheimer’s disease; App(NL-G-F) knock-in mice; Bile acids; Gut microbiome; Intestinal inflammation; Neuroinflammation; Probiotic; Prostaglandins; VSL#3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alzheimer Disease / etiology*
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / microbiology*
  • Alzheimer Disease / prevention & control
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Bile Acids and Salts / metabolism
  • Brain / metabolism*
  • Brain / pathology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Eicosanoids / metabolism
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Gliosis
  • Inflammation
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Probiotics / administration & dosage*
  • Probiotics / pharmacology*

Substances

  • Amyloid beta-Peptides
  • Bile Acids and Salts
  • Cytokines
  • Eicosanoids