Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J Neuroinflammation. 2024 Sep 12;21(1):221. doi: 10.1186/s12974-024-03220-6.
Postoperative cognitive dysfunction (POCD) is common following surgery in elderly patients. The role of the preoperative gut microbiota in POCD has attracted increasing attention, but the potential underlying mechanisms remain unclear. This research aimed to investigate the impact of the preoperative gut microbiota on POCD.
Herein, we analyzed the preoperative gut microbiota of POCD patients through a prospective specimen collection and retrospective blinded evaluation study. Then, we transferred the preoperative gut microbiota of POCD patients to antibiotic-treated rats and established POCD model by abdominal surgery to explore the impact of the preoperative gut microbiota on pre- and postoperative cognitive function and systemic inflammation. The gut microbiota was analyzed using 16S rRNA sequencing analysis. The Morris water maze test was performed to evaluate learning and memory abilities. The inflammatory cytokines TNF-α, IL-1β and IL-6 in the serum and hippocampus were measured by ELISA. Microglia were examined by immunofluorescence staining for Iba-1.
Based on the decrease in the postoperative MMSE score, 24 patients were identified as having POCD and were matched with 24 control patients. Compared with control patients, POCD patients exhibited higher BMI and lower preoperative MMSE score. The preoperative gut microbiota of POCD patients had lower bacterial richness but a larger distribution, decreased abundance of Firmicutes and increased abundance of Proteobacteria than did that of control patients. Compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients presented an increased abundance of Desulfobacterota, decreased cognitive function, increased levels of TNF-α and IL-1β in the serum, increased levels of TNF-α and greater microglial activation in the hippocampus. Additionally, correlation analysis revealed a positive association between the abundance of Desulfobacterota and the level of serum TNF-α in rats. Then, we performed abdominal surgery to investigate the impact of the preoperative gut microbiota on postoperative conditions, and the surgery did indeed cause POCD and inflammatory response. Notably, compared with rats that received preoperative fecal samples of control patients, rats that received preoperative fecal samples of POCD patients displayed exacerbated cognitive impairment; increased levels of TNF-α, IL-1β and IL-6 in the serum and hippocampus; and increased activation of microglia in the hippocampus.
Our findings suggest that the preoperative gut microbiota of POCD patients can induce preoperative and aggravate postoperative cognitive impairment and systemic inflammation in rats. Modulating inflammation by targeting the gut microbiota might be a promising approach for preventing POCD.
术后认知功能障碍（POCD）是老年患者手术后常见的问题。术前肠道微生物群在 POCD 中的作用引起了越来越多的关注，但潜在的机制仍不清楚。本研究旨在探讨术前肠道微生物群对 POCD 的影响。
通过前瞻性标本采集和回顾性盲法评估研究，分析 POCD 患者的术前肠道微生物群。然后，我们将 POCD 患者的术前肠道微生物群转移到接受抗生素治疗的大鼠体内，并通过腹部手术建立 POCD 模型，以探讨术前肠道微生物群对术前和术后认知功能和全身炎症的影响。使用 16S rRNA 测序分析肠道微生物群。通过 Morris 水迷宫试验评估学习和记忆能力。通过 ELISA 测量血清和海马中的炎症细胞因子 TNF-α、IL-1β 和 IL-6。通过免疫荧光染色 Iba-1 检测小胶质细胞。
根据术后 MMSE 评分下降，确定 24 名患者为 POCD，并与 24 名对照患者相匹配。与对照组患者相比，POCD 患者的 BMI 更高，术前 MMSE 评分更低。POCD 患者的术前肠道微生物群的细菌丰富度较低，但分布更大，厚壁菌门的丰度降低，变形菌门的丰度增加。与接受对照患者术前粪便样本的大鼠相比，接受 POCD 患者术前粪便样本的大鼠 Desulfobacterota 的丰度增加，认知功能下降，血清 TNF-α 和 IL-1β 水平升高，海马 TNF-α 水平升高，小胶质细胞激活增加。此外，相关性分析显示大鼠 Desulfobacterota 的丰度与血清 TNF-α 水平呈正相关。然后，我们进行了腹部手术，以研究术前肠道微生物群对术后情况的影响，手术确实导致了 POCD 和炎症反应。值得注意的是，与接受对照患者术前粪便样本的大鼠相比，接受 POCD 患者术前粪便样本的大鼠认知功能障碍加重；血清和海马 TNF-α、IL-1β 和 IL-6 水平升高；海马中小胶质细胞的激活增加。
我们的研究结果表明，POCD 患者的术前肠道微生物群可以在大鼠中引起术前和术后认知障碍和全身炎症，并加重术后认知障碍和全身炎症。通过靶向肠道微生物群调节炎症可能是预防 POCD 的一种有前途的方法。
