急性胰腺炎患者肠道微生态及其与病情严重程度的相关性: 一项前瞻性横断面研究

Correlation between Gut Microbiome and Disease Severity in Patients with Acute Pancreatitis: A Prospective Cross-sectional Study

  • 摘要:
      目的  探究急性胰腺炎(acute pancreatitis, AP)患者肠道菌群变化特征及其与病情严重程度的相关性。
      方法  本研究为前瞻性横断面研究。研究对象为2018年6月至2022年1月北京协和医院AP患者和健康志愿者。收集两组临床资料及粪便标本,对其肠道菌群16S rRNA进行DNA测序并进行生物信息学分析。比较两组肠道菌群差异,并采用受试者操作特征曲线分析肠道菌群与AP病情严重程度的相关性。
      结果  共入选符合纳入和排除标准的AP患者60例、健康志愿者20名。AP患者中,轻症、中度重症、重症患者各20例,住院期间转入ICU 22例,未转入ICU 38例。α多样性分析显示,AP患者肠道菌群Shannon指数低于健康志愿者(P<0.05);β多样性分析显示,AP患者肠道菌群结构异于健康志愿者。在门、科、属、种水平的比较中,AP患者与健康志愿者肠道菌群分布均存在差异。线性判别分析结果显示,包括大肠志贺菌属、肠球菌属和肠球菌科在内的多个菌群在AP患者中呈优势分布,而布劳特氏菌属和双歧杆菌属等菌群在健康志愿者中呈优势分布。功能分析提示AP患者肠道菌群中多种氨基酸合成受阻,菌群致病性与迁移能力增强。ICU患者与非ICU患者的亚组分析亦可观察到类似变化,ICU患者肠球菌表达增多,拟杆菌表达降低。受试者操作特征曲线显示,基于表达差异菌种计算的疾病概率(probability of disease, POD)指数识别AP患者、转入ICU的AP患者的曲线下面积分别为0.996、0.743。
      结论  AP患者肠道致病性菌群增多、有益菌减少。肠道菌群变化与AP病情严重程度相关,有望作为AP的新型生物标志物。

     

    Abstract:
      Objective  To investigate the gut microbiome composition and changes and its association with disease severity in patients with acute pancreatitis (AP).
      Methods  This study was a prospective cross-sectional analysis. The subjects of the study were AP patients in Peking Union Medical College Hospital from June 2018 to January 2022 and healthy volunteers. The clinical data and stool samples of the two groups were collected, the 16S rRNA of the gut microbiome was DNA sequenced, and bioinformatic analysis was performed. The differences in gut microbiome between the two groups were compared, and the correlation between the intestinal flora and the severity of AP was analyzed by receiver operating characteristic(ROC) curve.
      Results  A total of 60 AP patients and 20 healthy volunteers were enrolled. Among the AP patients, 20 were mild AP, 20 were moderately severe AP, and 20 were severe AP. During hospitalization, 22 cases were transferred to ICU, while 38 cases were not. In α diversity analysis, the Shannon index of AP patients was significant decreased compared to healthy volunteers (P < 0.05). β diversity of the two groups was significantly different. At the phylum, family, genus and species levels, there were also significant differences in the microbiome composition between the two groups. Linear discriminant analysis effect size analysis revealed that g_Escherichia-Shigella, g_Enterococcus, and f_Enterococcaceae were dominant in AP patients while g_Blautia, and g_Bifidobacterium were dominant in healthy volunteers. Function analysis found that multiple amino acid biosynthesis pathways were blocked in gut microbiome of AP patients, and potential pathogenicity and migration ability of gut microbiome increased significantly. In subgroup analysis, g_Enterococcus was increased and g_Bacteroidaceae was decreased in ICU patients compared to non-ICU patients. Based on the probability of disease index, the ROC curve showed that the area under the curve for identifying AP patients and AP patients transferred to ICU were 0.996 and 0.743.
      Conclusions  The pathogenic bacteria increased and the beneficial bacteria decreased in the gut microbiome of AP patients. Changes in gut microbiota are related to the severity of AP disease and therefore have the potential to be used as novel biomarkers for AP.

     

/

返回文章
返回