Neuroprotective Effects of Fecal Microbiota Transplantation on MPTP-induced Parkinson's Disease Mice: Gut Microbiota, Glial Reaction and TLR4/TNF-α Signaling Pathway

Brain Behav Immun. 2018 May;70:48-60. doi: 10.1016/j.bbi.2018.02.005. Epub 2018 Feb 20.

Abstract

Parkinson's disease (PD) patients display alterations in gut microbiota composition. However, mechanism between gut microbial dysbiosis and pathogenesis of PD remains unexplored, and no recognized therapies are available to halt or slow progression of PD. Here we identified that gut microbiota from PD mice induced motor impairment and striatal neurotransmitter decrease on normal mice. Sequencing of 16S rRNA revealed that phylum Firmicutes and order Clostridiales decreased, while phylum Proteobacteria, order Turicibacterales and Enterobacteriales increased in fecal samples of PD mice, along with increased fecal short-chain fatty acids (SCFAs). Remarkably, fecal microbiota transplantation (FMT) reduced gut microbial dysbiosis, decreased fecal SCFAs, alleviated physical impairment, and increased striatal DA and 5-HT content of PD mice. Further, FMT reduced the activation of microglia and astrocytes in the substantia nigra, and reduced expression of TLR4/TNF-α signaling pathway components in gut and brain. Our study demonstrates that gut microbial dysbiosis is involved in PD pathogenesis, and FMT can protect PD mice by suppressing neuroinflammation and reducing TLR4/TNF-α signaling.

Keywords: Glia; Gut-brain axis; Microbial dysbiosis; Neuroinflammation; Neurotransmitter; Parkinson’s disease; Short-chain fatty acids; TLR4/TNF-α signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain
  • Disease Models, Animal
  • Dysbiosis / metabolism
  • Dysbiosis / physiopathology
  • Fecal Microbiota Transplantation / methods*
  • Feces / microbiology
  • Gastrointestinal Microbiome / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia
  • Neuroglia / drug effects
  • Neuroprotective Agents
  • Parkinson Disease / physiopathology
  • Parkinson Disease / therapy*
  • RNA, Ribosomal, 16S / genetics
  • Toll-Like Receptor 4 / drug effects
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Neuroprotective Agents
  • RNA, Ribosomal, 16S
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha