关键词: NLRP3 inflammasome cefazolin gut dysbacteria neuroinflammation perioperative neurocognitive disorders probiotics

来  源:   DOI:10.3389/fnins.2023.1156453   PDF(Pubmed)

Abstract:
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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-1β (IL-1β), 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.
UNASSIGNED: 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.
摘要:
新数据表明,围手术期肠道菌群失调很普遍,可能与术后神经认知障碍(PND)有关。抗生素和益生菌是影响微生物群的关键因素。许多抗生素具有抗微生物和直接抗炎特性,可能会产生认知影响。据报道,NLRP3炎性体激活与认知缺陷有关。本研究旨在通过NLRP3途径确定益生菌对与围手术期肠道菌群失调相关的神经认知问题的影响和机制。
在随机分组中,对照试验,接受手术的成年雄性昆明小鼠给予头孢唑林,FOS+益生菌,CY-09,或四个不同实验队列中的安慰剂。恐惧条件(FC)测试评估学习和记忆。在进行FC测试以评估炎症反应(IR)和屏障系统的渗透性之后,提取海马和结肠,并收集粪便16s的rRNA。
手术后一周,手术/麻醉降低了冻结行为。头孢唑林减轻了这种偏角,但在手术后3周加重了术后冻结行为。益生菌改善手术/麻醉诱导的记忆缺陷和围手术期头孢唑啉诱导的术后记忆缺陷3周后。NLRP3,caspase-1,白细胞介素-1β(IL-1β),和白细胞介素-18(IL-18)水平在海马和结肠手术后1周增加,被CY-09和益生菌减毒,分别。
益生菌可以纠正手术/麻醉应激和头孢唑林单独引起的菌群失调和IR。这些发现表明,益生菌是维持肠道菌群平衡的有效方法,这可能减少NLRP3相关的炎症和减轻PND。
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