Long-term modification of gut microbiota by broad-spectrum antibiotics improves stroke outcome in rats
Chang Liu, Xi Cheng, Shanshan Zhong, Zhouyang Liu, Fangxi Liu, Xinyu Lin, Yinan Zhao, Meiting Guan, Ting Xiao, Jukka Jolkkonen, Ying Wang, Chuansheng Zhao
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.