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心脏手术后的术后谵妄与围手术期肠道微生物群失调相关:来自人类和抗生素治疗小鼠模型的证据。

Postoperative delirium after cardiac surgery associated with perioperative gut microbiota dysbiosis: Evidence from human and antibiotic-treated mouse model.

作者信息

Huang Peiying, Di Lichao, Cui Sichen, Wang Xueji, Cao Tianyu, Jiang Sufang, Huang Lining

机构信息

Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China.

Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, China; Key Laboratory of Clinical Neurology (Hebei Medical University), Ministry of Education, Shijiazhuang, Hebei, 050000, China.

出版信息

Anaesth Crit Care Pain Med. 2025 Apr;44(2):101484. doi: 10.1016/j.accpm.2025.101484. Epub 2025 Jan 23.

DOI:10.1016/j.accpm.2025.101484
PMID:39862968
Abstract

BACKGROUND

Research links gut microbiota to postoperative delirium (POD) through the gut-brain axis. However, changes in gut microbiota and fecal short-chain fatty acids (SCFAs) in POD patients during the perioperative period and their association with POD are unclear.

METHODS

We conducted a nested case-control study among patients undergoing off-pump coronary artery bypass grafting, focusing on POD as the main outcome. POD patients were matched 1:1 with non-POD patients based on sociodemographic characteristics, health, and diet. Fecal samples were collected pre- and post-surgery to assess gut microbiota and SCFAs changes. Postoperative fecal samples were transplanted into antibiotic-treated mice to evaluate delirium-like behavior and neuroinflammation.

RESULTS

Out of 120 patients, 60 were matched. Before surgery, gut microbiota in both groups was similar. After surgery, POD patients had lower alpha diversity and distinct microbiota compared to non-POD patients. LEfSe analysis showed POD was linked to increased opportunistic pathogens (Enterococcus) and decreased SCFAs producers (Bacteroides, Ruminococcus, etc.). SCFAs were significantly reduced in POD patients and negatively correlated with delirium severity and plasma inflammation. Mice receiving fecal transplants from POD patients exhibited delirium-like behavior and neuroinflammation.

CONCLUSIONS

Postoperative delirium is associated with gut microbiota dysbiosis, marked by an increase in opportunistic pathogens and a decrease in SCFA-producing genera.

REGISTRATION

Chinese Clinical Trial Registry ChiCTR2300070477.

摘要

背景

研究通过肠-脑轴将肠道微生物群与术后谵妄(POD)联系起来。然而,围手术期POD患者肠道微生物群和粪便短链脂肪酸(SCFA)的变化及其与POD的关联尚不清楚。

方法

我们在接受非体外循环冠状动脉搭桥术的患者中进行了一项巢式病例对照研究,主要关注POD。根据社会人口学特征、健康状况和饮食,将POD患者与非POD患者按1:1进行匹配。在手术前后收集粪便样本,以评估肠道微生物群和SCFA的变化。将术后粪便样本移植到经抗生素治疗的小鼠体内,以评估类似谵妄的行为和神经炎症。

结果

120例患者中,60例匹配成功。术前,两组患者的肠道微生物群相似。术后,与非POD患者相比,POD患者的α多样性较低,微生物群也不同。线性判别分析效应大小(LEfSe)分析表明,POD与机会性病原体(肠球菌)增加和SCFA产生菌(拟杆菌、瘤胃球菌等)减少有关。POD患者的SCFA显著降低,且与谵妄严重程度和血浆炎症呈负相关。接受POD患者粪便移植的小鼠表现出类似谵妄的行为和神经炎症。

结论

术后谵妄与肠道微生物群失调有关,其特征是机会性病原体增加,产生SCFA的菌属减少。

注册信息

中国临床试验注册中心ChiCTR2300070477

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