Probiotic Pediococcus pentosaceus ameliorates MPTP-induced oxidative stress via regulating the gut microbiota-gut-brain axis

Front Cell Infect Microbiol. 2022 Nov 9;12:1022879. doi: 10.3389/fcimb.2022.1022879. eCollection 2022.

Abstract

Recent evidence demonstrated that functional bacteria were involved in the regulation of Parkinson's disease (PD). However, the mechanism of probiotics in improving PD was unclear. Here the antioxidant effect and the mechanism of probiotics Pediococcus pentosaceus (PP) on PD were studied by regulating the gut-brain axis. In this study, male C57BL/6J mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally to establish a PD model and were then treated with PP for 4 weeks. Subsequently, a series of neurobehavioral tests to evaluate the motor function of the mice was performed. Additionally, degeneration of dopaminergic neurons, accumulation of α-synuclein, the production of an oxidative stress response, and the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway-related proteins were evaluated. Moreover, the gut microbial composition and the level of metabolite γ-aminobutyric acid (GABA) were assessed. The results showed that PP treatment could improve MPTP-induced motor deficits, the degeneration of dopaminergic neurons, and the accumulation of α-synuclein. Moreover, PP treatment significantly increased the levels of SOD1, Gpx1, and Nrf2, while it decreased the levels of Keap1 in the brain of MPTP-induced mice. Notably, PP treatment improved the gut microbial dysbiosis and increased the level of GABA in MPTP-induced mice. These findings indicated that PP might represent a promising candidate, due to the metabolite of GABA, that could be used for the treatment of PD.

Keywords: Nrf2 signaling; P. pentosaceus; Parkinson’s disease; gut microbiota; oxidative stress; γ-aminobutyric acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology
  • Animals
  • Brain-Gut Axis
  • Gastrointestinal Microbiome* / physiology
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / metabolism
  • Oxidative Stress
  • Parkinson Disease*
  • Pediococcus pentosaceus / metabolism
  • Probiotics*
  • alpha-Synuclein / metabolism
  • alpha-Synuclein / pharmacology
  • gamma-Aminobutyric Acid / metabolism

Substances

  • alpha-Synuclein
  • NF-E2-Related Factor 2
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Kelch-Like ECH-Associated Protein 1
  • gamma-Aminobutyric Acid