PMID- 37179548 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230919 IS - 1662-4548 (Print) IS - 1662-453X (Electronic) IS - 1662-453X (Linking) VI - 17 DP - 2023 TI - The contribution of probiotics for the double-edge effect of cefazolin on postoperative neurocognitive disorders by rebalancing the gut microbiota. PG - 1156453 LID - 10.3389/fnins.2023.1156453 [doi] LID - 1156453 AB - INTRODUCTION: Emerging data suggest that perioperative gut dysbiosis is prevalent and may be associated with postoperative neurocognitive disorders (PND). Antibiotics and probiotics are key factors influencing the microbiota. Many antibiotics have anti-microorganisms and direct anti-inflammatory properties, which may have cognitive repercussions. NLRP3 inflammasome activation has been reported to be involved with cognitive deficits. This study aimed to determine the effect and mechanism of probiotics on neurocognitive problems associated with perioperative gut dysbiosis by the NLRP3 pathway. METHODS: In a randomized, controlled trial, adult male Kunming mice undergoing surgery were administered cefazolin, FOS + probiotics, CY-09, or a placebo in four distinct experimental cohorts. Fear conditioning (FC) tests evaluate learning and memory. Following FC tests to evaluate inflammatory response (IR) and the permeability of barrier systems, the hippocampus and colon were extracted, and feces were collected for 16 s rRNA. RESULTS: One week after surgery, surgery/anesthesia decreased the frozen behavior. Cefazolin attenuated this declination but aggravated postoperative freezing behavior 3 weeks after surgery. Probiotics ameliorated surgery/anesthesia-induced memory deficits and perioperative cefazolin-induced postoperative memory deficits 3 weeks after surgery. NLRP3, caspase-1, Interleukin-1beta (IL-1beta), and Interleukin-18 (IL-18) levels were increased 1 week after the hippocampus and colon surgery, which were attenuated by CY-09 and probiotics, respectively. DISCUSSION: Probiotics could correct dysbacteria and IR caused by surgery/anesthesia stress and cefazolin alone. These findings imply that probiotics are an efficient and effective way of maintaining the balance of gut microbiota, which may reduce NLRP3-related inflammation and alleviate PND. CI - Copyright (c) 2023 Zhang, Wu, Liu, Huang, Zhou and Liang. FAU - Zhang, Tianyao AU - Zhang T AD - Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China. AD - Department of Anesthesiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China. FAU - Wu, Xiaochu AU - Wu X AD - National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China. FAU - Liu, Bin AU - Liu B AD - Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China. AD - Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu, China. FAU - Huang, Han AU - Huang H AD - Department of Anesthesiology and Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital of Sichuan University, Chengdu, Sichuan, China. FAU - Zhou, Cheng AU - Zhou C AD - Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China. AD - Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, West China Hospital of Sichuan University, Chengdu, China. FAU - Liang, Peng AU - Liang P AD - Department of Anesthesiology, West China Hospital of Sichuan University, Chengdu, China. AD - Day Surgery Center, General Practice Medical Center, West China Hospital, Sichuan University and the Research Units of West China (2018RU012), Chinese Academy of Medical Sciences, Chengdu, China. LA - eng PT - Journal Article DEP - 20230427 PL - Switzerland TA - Front Neurosci JT - Frontiers in neuroscience JID - 101478481 PMC - PMC10174111 OTO - NOTNLM OT - NLRP3 inflammasome OT - cefazolin OT - gut dysbacteria OT - neuroinflammation OT - perioperative neurocognitive disorders OT - probiotics COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/05/14 13:10 MHDA- 2023/05/14 13:11 PMCR- 2023/01/01 CRDT- 2023/05/14 11:54 PHST- 2023/02/01 00:00 [received] PHST- 2023/04/04 00:00 [accepted] PHST- 2023/05/14 13:11 [medline] PHST- 2023/05/14 13:10 [pubmed] PHST- 2023/05/14 11:54 [entrez] PHST- 2023/01/01 00:00 [pmc-release] AID - 10.3389/fnins.2023.1156453 [doi] PST - epublish SO - Front Neurosci. 2023 Apr 27;17:1156453. doi: 10.3389/fnins.2023.1156453. eCollection 2023.