Engineered commensal bacteria prevent systemic inflammation-induced memory impairment and amyloidogenesis via producing GLP-1

Appl Microbiol Biotechnol. 2018 Sep;102(17):7565-7575. doi: 10.1007/s00253-018-9155-6. Epub 2018 Jun 28.

Abstract

The anti-obesity drug GLP-1 has been proven to have an impact on central nervous system, while its extremely short half-life greatly limited its use. In this study, our group constructed two engineering strains MG1363-pMG36e-GLP-1 and VNP20009-pLIVE-GLP-1 to continuously express GLP-1, and supplementation of these strains, especially MG1363-pMG36e-GLP-1, had significantly restored the spatial learning and memory impairment of mice caused by LPS (p < 0.05), suppressed glia activation and Aβ accumulation, and downregulated inflammatory expressions of COX-2, TLR-4, TNF-a, and IL-1β. In addition, MG1363-pMG36e-GLP-1 had significantly blocked the translocation of NF-κB signal and inhibited the phosphorylation of redox-sensitive cytoplasmic signalings of MAPKs and PI3K/AKT. These data suggest that MG1363-pMG36e-GLP-1 could be used as a safe and effective nonabsorbed oral treatment for neuroinflammation-related diseases such as Alzheimer's disease (AD).

Keywords: Alzheimer’s disease (AD); COX-2; GLP-1; MG1363-pMG36e-GLP-1; TLR-4.

MeSH terms

  • Animals
  • Bacteria / genetics*
  • Bacteria / metabolism
  • Glucagon-Like Peptide 1 / administration & dosage
  • Glucagon-Like Peptide 1 / genetics*
  • Glucagon-Like Peptide 1 / metabolism
  • Lipopolysaccharides
  • Memory Disorders / chemically induced
  • Memory Disorders / therapy*
  • Mice
  • Microorganisms, Genetically-Modified / genetics
  • Microorganisms, Genetically-Modified / metabolism*

Substances

  • Lipopolysaccharides
  • Glucagon-Like Peptide 1