Abstract
Emerging evidence suggests that anesthesia and surgery may induce gut dysbiosis. Gut dysbiosis leads to imbalance in circulating contents of microbiota-derived metabolites and disrupts the integrity of the blood-brain barrier (BBB), contributing to postoperative cognitive dysfunction (POCD). The composition of gut microbiota may be influenced by various antibiotics. However, how perioperative use of antibiotics affects POCD needs more explorations. In the present study, we explored the effect of cefazolin, a common antibiotic used in perioperative period, on cognitive function, BBB integrity, gut bacteria and short chain fatty acids (SCFAs), a group of widely studied metabolites in aged mice, using 18-month-old male mice. Significant BBB disruptions and decreased levels of tight junction proteins, zonula occludens-1 (ZO-1) and Occludin (OCLN) were seen in the mice of POCD model. Cefazolin treatment attenuated these changes induced by anesthesia and surgery. Furthermore, cefazolin reversed the changes in several fecal bacteria (β-, γ/δ-, ε-Proteobacteria, and Bacteroidetes) as determined by qPCR tests. Analysis of plasma SCFAs showed that almost all types of SCFAs were reduced in POCD and cefazolin administration reversed the changes in expression of the two most abundant SCFAs (acetic and propionic acids). In conclusion, this study demonstrated that cefazolin improved POCD. Mechanistically, cefazolin suppressed the disruption of BBB, gut microbiota or SCFAs, thereby ameliorating POCD.
Highlights
Postoperative cognitive dysfunction (POCD), a serious complication after anesthesia and surgery in the elderly, causes delayed recovery, increased mortality and social burden (Hovens et al, 2012)
We explored the effect of cefazolin, a common antibiotic used in perioperative period, on cognitive function, blood-brain barrier (BBB) integrity, gut bacteria and short chain fatty acids (SCFAs), a group of widely studied metabolites in aged mice, using 18-month-old male mice
Cefazolin reversed the abnormal changes in the relative abundance of several gut bacteria (Bacteroidetes, β-Proteobacteria, γ/δProteobacteria, and ε-Proteobacteria) and the concentrations of plasma SCFAs
Summary
Postoperative cognitive dysfunction (POCD), a serious complication after anesthesia and surgery in the elderly, causes delayed recovery, increased mortality and social burden (Hovens et al, 2012). The effect of perioperative use of antibiotics on gut microbiota and cognitive function is less understood. Liang et al firstly elucidated that cefazolin administration based on clinical practice (30 min before surgery and 5 days after surgery) could attenuate surgery-induced cognitive impairments and neuroinflammation in young mice. The influence of cefazolin on cognitive function, gut microbiota and associated metabolites in aged mice is worthy of further exploration. We investigated the effect of cefazolin on anesthesia and surgery-induced cognitive impairments and BBB function in aged mice. We explored cefazolin-induced alterations of gut bacteria and important metabolites, short-chain fatty acids (SCFAs), and analyze their possible effect on BBB function and cognitive performance in the POCD model
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