Transplantation of fecal microbiota rich in short chain fatty acids and butyric acid treat cerebral ischemic stroke by regulating gut microbiota

Pharmacol Res. 2019 Oct:148:104403. doi: 10.1016/j.phrs.2019.104403. Epub 2019 Aug 16.

Abstract

The gut microbiota and its short chain fatty acid (SCFA) metabolites have been established to play an important protective role against neurodegenerative diseases. Our previous study demonstrated that cerebral ischemic stroke triggers dysfunctional gut microbiota and increased intestinal permeability. In this study, we aimed to clarify the mechanism by which gut microbiota and SCFAs can treat cerebral ischemic stroke in rat middle cerebral artery occlusion models and use the information to develop new therapies. Our results show that oral administration of non-absorbable antibiotics reduced neurological impairment and the cerebral infarct volume, relieved cerebral edemas, and decreased blood lipid levels by altering the gut microbiota. We also found that ischemic stroke decreased intestinal levels of SCFAs. And that transplanting fecal microbiota rich in these metabolites was an effective means of treating the condition. Compared with other SCFAs, butyric acid showed the highest negative correlation with ischemic stroke. Supplementation with butyric acid treated models of ischemic stroke effectively by remodeling the gut microbiota, enriching the beneficial Lactobacillus, and repairing the leaky gut. In conclusion, interfering with the gut microbiota by transplanting fecal bacteria rich in SCFAs and supplementing with butyric acid were found to be effective treatments for cerebral ischemic stroke.

Keywords: Butyric acid; Cerebral ischemic stroke; Fecal microbiota transplantation; Gut microbiota; Short chain fatty acids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / microbiology*
  • Brain Ischemia / therapy*
  • Butyric Acid / pharmacology*
  • Fatty Acids, Volatile / pharmacology*
  • Fecal Microbiota Transplantation / methods
  • Feces / microbiology
  • Gastrointestinal Microbiome / physiology*
  • Lactobacillus / physiology
  • Male
  • Microbiota / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Stroke / microbiology*
  • Stroke / therapy*

Substances

  • Fatty Acids, Volatile
  • Butyric Acid