脓毒症患儿肠道菌群结构与炎症反应相关性的前瞻性队列研究

Association between the structure of intestinal flora and inflammatory response in children with sepsis:a prospective cohort study

目的 探讨脓毒症患儿肠道菌群结构特征及其与炎症反应的相关性。方法 采用前瞻性队列研究方法,纳入2021年12月—2023年1月收治的脓毒症患儿为研究对象(设为脓毒症组),选择同期住院的感染非脓毒症患儿为对照(设为非脓毒症组)。比较两组患儿肠道菌群分布特征、外周白细胞(white blood cell,WBC)计数、C-反应蛋白(C-reactive protein,CRP)、细胞因子水平的差异,并将大便菌群相对丰度与WBC计数、CRP、细胞因子水平进行相关性分析。结果 属水平上,脓毒症组阿克曼氏菌属、瘤胃球菌属及另枝杆菌属相对丰度低于非脓毒症组,肠球菌属、链球菌属、葡萄球菌属相对丰度高于非脓毒症组(P<0.05)。门水平上,脓毒症患儿小儿危重症评分≤70分组以变形菌门为优势菌门(37.46%),71~80分组和81~90分组优势菌门为厚壁菌门(分别为72.20%、43.88%)。属水平上,18例标本中5例标本单一菌群相对丰度超过50%。脓毒症组WBC计数、CRP、白介素(interleukin,IL)-6、IL-10、肿瘤坏死因子-α水平高于非脓毒症组(P<0.05)。Spearman秩相关性分析显示:在属水平上,脓毒症组瘤胃球属、另枝杆菌属、副萨特氏菌属相对丰度与WBC计数、CRP、IL-6水平均呈负相关(P<0.05);肠球菌属相对丰度与CRP水平呈正相关(P<0.01);链球菌属、葡萄球菌属等相对丰度与CRP、IL-6水平均呈正相关(P<0.05);链球菌属相对丰度与WBC计数呈正相关(P<0.05)。结论 脓毒症患儿肠道菌群呈紊乱状态,且随病情程度不同具有特征性;脓毒症患儿肠道菌群结构改变与机体炎症反应具有相关性。

Objective To investigate the structural characteristics of intestinal flora in children with sepsis and its association with inflammatory response.Methods A prospective cohort study was conducted.The children with sepsis who were admitted from December 2021 to January 2023 were enrolled as the sepsis group,and the children with non-sepsis who were admitted during the same period were enrolled as the non-sepsis group.The two groups were compared in terms of the distribution characteristics of intestinal flora,peripheral white blood cell count(WBC),C reactive protein(CRP),and cytokines,and the correlation of the relative abundance of fecal flora with WBC,CRP,and cytokines was analyzed.Results At the genus level,compared with the non-sepsis group,the sepsis group had significantly lower relative abundance of Akkermansia,Ruminococcus,and Alistipes and significantly higher relative abundance of Enterococcus,Streptococcus,and Staphylococcus(P<0.05).At the phylum level,Proteobacteria was the dominant phylum(37.46%)in the group of children with a score of≤70 from the Pediatric Critical Illness Score(PICS),and Firmicutes was the dominant phylum in the group of children with a score of 71-80 or 81-90 from the PICS(72.20%and 43.88%,respectively).At the genus level,among the 18 specimens,5 had a relative abundance of>50%for a single flora.Compared with the non-sepsis group,the sepsis group had significant higher levels of WBC,CRP,interleukin-6(IL-6),interleukin-10(IL-10),and tumor necrosis factor-α(P<0.05).The Spearman's rank correlation analysis showed that at the genus level,the relative abundance of Ruminococcus,Alistipes,and Parasutterella in the sepsis group was negatively correlated with the levels of WBC,CRP,and IL-6(P<0.05);the relative abundance of Enterococcus was positively correlated with the CRP level(P<0.01);the relative abundance of Streptococcus and Staphylococcus was positively correlated with the levels of CRP and IL-6(P<0.05);the relative abundance of Streptococcus was positively correlated with WBC(P<0.05).Conclusions Intestinal flora disturbance is observed in children with sepsis,and its characteristics vary with the severity of the disease.The structural changes of intestinal flora are correlated with inflammatory response in children with sepsis.