Long-term modification of gut microbiota by broad-spectrum antibiotics improves stroke outcome in rats

Stroke Vasc Neurol. 2022 Oct;7(5):381-389. doi: 10.1136/svn-2021-001231. Epub 2022 May 16.

Abstract

Background: The brain-gut axis is a major regulator of the central nervous system. We investigated the effects of treatment with broad-spectrum antibiotics on gut and brain inflammation, infarct size and long-term behavioral outcome after cerebral ischemia in rats.

Methods: Rats were treated with broad-spectrum antibiotics (ampicillin, vancomycin, ciprofloxacin, meropenem and metronidazole) for 4 weeks before the endothelin-1 induced ischemia. Treatment continued for 2 weeks until the end of behavioral testing, which included tapered ledged beam-walking, adhesive label test and cylinder test. Gut microbiome, short-chain fatty acids and cytokine levels were measured together with an assessment of infarct size, neuroinflammation and neurogenesis.

Results: The results revealed that the antibiotics exerted a clear impact on the gut microbiota. This was associated with a decrease in systemic and brain cytokine levels, infarct size and apoptosis in the perilesional cortex and improved behavioral outcome.

Conclusion: Our results highlighted the significant relationship between intestinal microbiota and beneficial neuro-recovery after ischemic stroke.

Keywords: Cerebral Infarction; Stroke; Stroke Rehabilitation.

MeSH terms

  • Ampicillin / pharmacology
  • Animals
  • Anti-Bacterial Agents
  • Ciprofloxacin / pharmacology
  • Cytokines
  • Endothelin-1 / pharmacology
  • Fatty Acids, Volatile
  • Gastrointestinal Microbiome*
  • Infarction / complications
  • Meropenem / pharmacology
  • Metronidazole / pharmacology
  • Rats
  • Stroke* / complications
  • Stroke* / drug therapy
  • Vancomycin / pharmacology

Substances

  • Ampicillin
  • Anti-Bacterial Agents
  • Ciprofloxacin
  • Cytokines
  • Endothelin-1
  • Fatty Acids, Volatile
  • Meropenem
  • Metronidazole
  • Vancomycin