Abstract
Gut microbiota is closely associated with the occurrence of neuropsychiatric disorders. Antibiotics are frequently used to prevent pathogen infection in patients with brain ischemia. To understand the impact of prophylactic antibiotic treatment for patients with brain ischemia, we examined the effects of orally administered vancomycin and ampicillin on cognitive function and gut microbiota composition in mice with transient global forebrain ischemia (tIsc). tIsc operation and orally gavaged vancomycin mildly and moderately caused cognitive impairment, respectively. However, the exposure of mice with tIsc to vancomycin or ampicillin severely impaired cognitive function in the Y-maze, novel object recognition, and Banes maze tasks. Furthermore, their treatments induced NF-κB activation as well as active microglia (NF-κB+/Iba1+ and LPS+/Iba1+ cells) and apoptotic (caspase 3+/NeuN+) cell population in the hippocampus, whereas the brain-derived neurotrophic factor (BDNF)+/NeuN+ cell populations decreased. These treatments also caused colitis and gut dysbiosis. They increased the population of Proteobacteria including Enterobacter xiangfangenesis. Orally delivered fecal transplantation of vancomycin-treated mice with or without tIsc and oral gavage of Enterobacter xiangfangenesis also significantly deteriorated the cognitive impairment and colitis in transplanted mice with tIsc. These findings suggest that oral administration of antibiotics can deteriorate cognitive impairment with gut dysbiosis in patients with brain ischemia.
Highlights
Brain ischemia occurs when there is an insufficient amount of blood flow to the brain (Clemens et al, 1997; Bramlett and Dietrich, 2004)
Benakis et al (2016) reported that orally administered amoxicillin/clavulanic acid reduces ischemic brain injury in mice by regulating gut microbiota composition, while Dong et al (2017) reported that orally prophylactic treatment with an antibiotic cocktail consisting of chlortetracycline, penicillin VK, and vancomycin could not reduce microbial infection, and Winek et al (2016) reported that the depletion of gut microbiota by oral prophylactic treatment with an antibiotic cocktail consisting of ampicillin, vancomycin, ciprofloxacin, imipenem, and metronidazole deteriorates the outcome after murine stroke
To understand the effects of the antibiotics used in patients with brain ischemia on the occurrence of cognitive impairment, we induced transient global forebrain ischemia in mice, orally administered ampicillin or vancomycin, and examined cognitive function (Figure 1A)
Summary
Brain ischemia occurs when there is an insufficient amount of blood flow to the brain (Clemens et al, 1997; Bramlett and Dietrich, 2004). This deprives brain tissue of oxygen and nutrients, resulting in brain cell death, cerebral infarction, or ischemic stroke. Benakis et al (2016) reported that orally administered amoxicillin/clavulanic acid reduces ischemic brain injury in mice by regulating gut microbiota composition, while Dong et al (2017) reported that orally prophylactic treatment with an antibiotic cocktail consisting of chlortetracycline, penicillin VK, and vancomycin could not reduce microbial infection, and Winek et al (2016) reported that the depletion of gut microbiota by oral prophylactic treatment with an antibiotic cocktail consisting of ampicillin, vancomycin, ciprofloxacin, imipenem, and metronidazole deteriorates the outcome after murine stroke. Benakis et al (2016) reported that orally administered amoxicillin/clavulanic acid reduces ischemic brain injury in mice by regulating gut microbiota composition, while Dong et al (2017) reported that orally prophylactic treatment with an antibiotic cocktail consisting of chlortetracycline, penicillin VK, and vancomycin could not reduce microbial infection, and Winek et al (2016) reported that the depletion of gut microbiota by oral prophylactic treatment with an antibiotic cocktail consisting of ampicillin, vancomycin, ciprofloxacin, imipenem, and metronidazole deteriorates the outcome after murine stroke. Singh et al (2016) reported that fecal microbiota transplantation of healthy mice into middle cerebral artery (MCA) occlusion-operated mice alleviated the stroke outcome
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
