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肠道微生物群落的异常组成导致小鼠腹部手术后出现类似谵妄的行为。

Abnormal composition of gut microbiota contributes to delirium-like behaviors after abdominal surgery in mice.

机构信息

Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Department of Hand Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

CNS Neurosci Ther. 2019 Jun;25(6):685-696. doi: 10.1111/cns.13103. Epub 2019 Jan 24.

Abstract

AIMS

Anesthesia and surgery can cause delirium-like symptoms postoperatively. Increasing evidence suggests that gut microbiota is a physiological regulator of the brain. Herein, we investigated whether gut microbiota plays a role in postoperative delirium (POD).

METHODS

Mice were separated into non-POD and POD phenotypes after abdominal surgery by applying hierarchical clustering analysis to behavioral tests. Fecal samples were collected, and 16S ribosomal RNA gene sequencing was performed to detect differences in gut microbiota composition among sham, non-POD, and POD mice. Fecal bacteria from non-POD and POD mice were transplanted into antibiotics-induced pseudo-germ-free mice to investigate the effects on behaviors.

RESULTS

α-diversity and β-diversity indicated differences in gut microbiota composition between the non-POD and POD mice. At the phylum level, the non-POD mice had significantly higher levels of Tenericutes, which were not detected in the POD mice. At the class level, levels of Gammaproteobacteria were higher in the POD mice, whereas the non-POD mice had significantly higher levels of Mollicutes, which were not detected in the POD mice. A total of 20 gut bacteria differed significantly between the POD and non-POD mice. Interestingly, the pseudo-germ-free mice showed abnormal behaviors prior to transplant. The pseudo-germ-free mice that received fecal bacteria transplants from non-POD mice but not from POD mice showed improvements in behaviors.

CONCLUSIONS

Abnormal gut microbiota composition after abdominal surgery may contribute to the development of POD. A therapeutic strategy that targets gut microbiota could provide a novel alterative for POD treatment.

摘要

目的

麻醉和手术会导致术后出现类似谵妄的症状。越来越多的证据表明,肠道微生物群是大脑的生理调节剂。在此,我们研究了肠道微生物群是否在术后谵妄(POD)中发挥作用。

方法

通过对行为测试进行层次聚类分析,将接受腹部手术后的小鼠分为非 POD 和 POD 表型。收集粪便样本,并进行 16S 核糖体 RNA 基因测序,以检测假手术、非 POD 和 POD 小鼠肠道微生物群组成的差异。将非 POD 和 POD 小鼠的粪便细菌移植到抗生素诱导的假无菌小鼠中,以研究其对行为的影响。

结果

α多样性和β多样性表明非 POD 和 POD 小鼠之间的肠道微生物群组成存在差异。在门水平上,非 POD 小鼠的厚壁菌门水平明显较高,而 POD 小鼠则未检测到。在纲水平上,POD 小鼠的γ变形菌纲水平较高,而非 POD 小鼠的柔膜菌纲水平明显较高,而 POD 小鼠则未检测到。POD 和非 POD 小鼠之间共有 20 种肠道细菌存在显著差异。有趣的是,假无菌小鼠在移植前就出现了异常行为。接受非 POD 小鼠而不是 POD 小鼠粪便细菌移植的假无菌小鼠的行为得到改善。

结论

腹部手术后肠道微生物群组成的异常可能导致 POD 的发生。针对肠道微生物群的治疗策略可能为 POD 的治疗提供一种新的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/43b3/6515708/f0d37ef6c210/CNS-25-685-g001.jpg

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