Preoperative fasting confers protection against intestinal ischaemia/reperfusion injury by modulating gut microbiota and their metabolites in a mouse model
Preoperative fasting confers protection against intestinal ischaemia/reperfusion injury by modulating gut microbiota and their metabolites in a mouse model
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术前禁食通过调节小鼠模型中的肠道微生物群及其代谢物来预防肠道缺血/再灌注损伤
DOI：
10.1016/j.bja.2021.11.025
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发表时间：
2022-02-24
影响因子：
9.8
通讯作者：
Li，Cai
中科院分区：
文献类型：
--
作者：
Huang，Wenfang;Yan，Yu;Li，Cai
肠缺血/再灌注损伤（intestinal ischaemia/reperfusion injury，I/R）是一种严重的外科并发症，发病率和死亡率高。术前禁食可能赋予保护肠道I/R损伤通过改变肠道菌群和各自的metabolites.MethodsAn肠道I/R小鼠模型的组成，并进行术前禁食24小时或fedad自由采食。采用组织学检查和生存分析评估肠I/R损伤。收集粪便样品进行16 S rDNA测序和代谢组学分析。进行禁食和非禁食小鼠和人的粪便移植以评估肠道微生物群对肠道I/R的影响。结果术前禁食可减轻肠I/R损伤，提高小鼠存活率（P<0.0 0 1）。此外，16 S rDNA测序显示，术前禁食增加了肠道I/R后肠道微生物群的多样性并重组了其组成。接受禁食小鼠和人类微生物群的小鼠比接受进食受试者微生物群的小鼠表现出更少的肠道损伤。代谢组学分析显示，禁食组和进食组之间的肠道微生物代谢产物谱不同。具体地，岩芹酸的浓度在禁食组中显著更高（P=0.009）。petroselinic acid治疗肠I/R小鼠减轻肠道损伤in vivo和减少细胞凋亡通过介导AMP活化蛋白激酶哺乳动物雷帕霉素靶蛋白P70 S6 K信号involved.ConclusionsPreoperative禁食保护肠道I/R损伤通过调节肠道菌群和petroselinic酸，这表明一种新的治疗策略。
BackgroundIntestinal ischaemia/reperfusion (I/R) injury is a grave surgical event with high morbidity and mortality. Preoperative fasting might confer protection against intestinal I/R injury by altering the composition of gut microbiota and their respective metabolites.MethodsAn intestinal I/R mouse model was established and subjected to preoperative fasting for 24 h or fedad libitum. Intestinal I/R injury was assessed using histological examination and survival analysis. Faecal samples were collected for 16S rDNA sequencing and metabolomic analysis. Faecal transplantation of fasted and non-fasted mice and humans was conducted to evaluate the effects of gut microbiota on intestinal I/R. Murine small intestinal cells wecre subjected to oxygen and glucose deprivation/reoxygenation as anin vitroI/R model.ResultsPreoperative fasting protected against intestinal I/R injury and improved survival in mice (P<0.001). In addition, 16S rDNA sequencing revealed that preoperative fasting increased the diversity and restructured the composition of the gut microbiota after intestinal I/R. Mice that received microbiota from fasted mice and humans showed less intestinal damage than those that received microbiota from fed subjects. Metabolomic analysis showed that the profiles of gut microbial metabolites differed between fasted and fed groups. Specifically, the concentration of petroselinic acid was significantly higher in the fasted group (P=0.009). Treatment of intestinal I/R mice with petroselinic acid alleviated intestinal injuryin vivoand decreased cell apoptosis by mediating AMP-activated protein kinase–mammalian target of rapamycin–P70S6K signalingin vitro.ConclusionsPreoperative fasting protected against intestinal I/R injury by modulating gut microbiota and petroselinic acid, suggesting a novel therapeutic strategy.