Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 80, Issue -, Pages 605-615Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2019.05.006
Keywords
Gut microbiome; Intestinal dysbacteriosis; Postoperative cognitive dysfunction
Categories
Funding
- National Natural Science Foundation of China [81571030, 81771133]
- Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support [20171916]
- Shanghai Pudong New Area Municipal Commission of Health and Family Planning Funding [PW2016D-4]
- Shanghai Jiao Tong University integration founding of Medicine and Engineering [YG2017MS53]
- Shanghai Shenkang Hospital Development Center Funding [SHDC12017X11]
- Renji Hospital Clinical Innovation Foundation [PYMDT-007]
- Shanghai Municipal Commission of Health and Family Planning Funding for Key Developing Disciplines [2015ZB0101]
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Background Postoperative cognitive dysfunction (POCD) is associated with increased morbidity and mortality and has become a major concern for patients and caregivers. POCD is most common in older patients. Previous studies demonstrated that the gut microbiome affects cognitive function and behaviour, and perioperative factors, including the operation itself, antibiotics, opioids or acid-inducing drugs, affect the gut microbiome. Thus, we hypothesised that intestinal dysbacteriosis caused by anaesthesia/surgery induces POCD. Methods: Tibial fracture internal fixation was performed in 18-month-old C57BL/6 mice under isoflurane anaesthesia to establish the POCD model. The Morris water maze was used to measure reference memory after anaesthesia/surgery. High-throughput sequencing of 16S rRNA from faecal samples was used to investigate changes in the abundance of intestinal bacteria after anaesthesia/surgery. To confirm the role of the gut microbiome in POCD, we pretreated mice with compound antibiotics or mixed probiotics (VSL#3). Anaesthesia/ surgery impaired reference memory and induced intestinal dysbacteriosis in aged mice. Results: The 16S rRNA sequencing data revealed 37 genera (18 families) of bacteria that changed in abundance after anaesthesia/surgery. Pretreating mice with compound antibiotics or mixed probiotics (VSL#3) prevented the learning and memory deficits induced by anaesthesia/surgery. We further conducted quantitative real-time polymerase chain reaction (qRT-PCR) of 22 common types of bacteria among the 37 total types to verify the results of bacterial flora changes after anaesthesia/surgery. Numbers of 8 types of bacteria changed after anaesthesia/surgery but returned to normal after treatment with a mix of probiotics. Conclusions: Our data suggest that deficits in reference memory induced by anaesthesia/surgery are mediated by intestinal dysbacteriosis.
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