Gut microbiota manipulation through probiotics oral administration restores glucose homeostasis in a mouse model of Alzheimer's disease

Neurobiol Aging. 2020 Mar;87:35-43. doi: 10.1016/j.neurobiolaging.2019.11.004. Epub 2019 Nov 11.

Abstract

Cerebral glucose homeostasis deregulation has a role in the pathogenesis and the progression of Alzheimer's disease (AD). Current therapies delay symptoms without definitively curing AD. We have previously shown that probiotics counteract AD progression in 3xTg-AD mice modifying gut microbiota and inducing energy metabolism and glycolysis-gluconeogenesis. Ameliorated cognition is based on higher neuroprotective gut hormones concentrations, reduced amyloid-β burden, and restored proteolytic pathways. Here, we demonstrate that probiotics oral administration improves glucose uptake in 3xTg-AD mice by restoring the brain expression levels of key glucose transporters (GLUT3, GLUT1) and insulin-like growth factor receptor β, in accordance with the diminished phosphorylation of adenosine monophosphate-activated protein kinase and protein-kinase B (Akt). In parallel, phosphorylated tau aggregates decrease in treated mice. Probiotics counteract the time-dependent increase of glycated hemoglobin and the accumulation of advanced glycation end products in AD mice, consistently with memory improvement. Collectively, our data elucidate the mechanism through which gut microbiota manipulation ameliorates impaired glucose metabolism in AD, finally delaying the disease progression.

Keywords: AGEs; Alzheimer's disease; Glucose metabolism; Probiotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / etiology
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / microbiology
  • Alzheimer Disease / therapy*
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Brain / metabolism*
  • Disease Models, Animal
  • Energy Metabolism / drug effects
  • Gastrointestinal Microbiome*
  • Glucose / metabolism*
  • Glucose Transporter Type 1 / metabolism
  • Glucose Transporter Type 3 / metabolism
  • Glycolysis / drug effects
  • Homeostasis*
  • Mice, Transgenic
  • Probiotics / administration & dosage*
  • Probiotics / pharmacology*
  • tau Proteins / metabolism

Substances

  • Amyloid beta-Peptides
  • Glucose Transporter Type 1
  • Glucose Transporter Type 3
  • Slc2a1 protein, mouse
  • Slc2a3 protein, mouse
  • tau Proteins
  • Glucose