Table_1_Gut Microbiome of Children and Adolescents With Primary Sclerosing Cholangitis in Association With Ulcerative Colitis.docx

Few studies reported the relation of intestinal microbiome composition and diversity in pediatric patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). In this cross-sectional study, we selected patients younger than 19 years old from the pediatric gastroenterology and hepatology outpatient clinic of a tertiary hospital to describe the intestinal microbiome of pediatric patients with PSC associated or not to UC. Patients were divided in PSC, PSC+UC, and UC diagnosis. A stool sample was collected from each patient (n=30) and from a healthy relative/neighbor (n=23). The microbiome composition was assessed using MiSeq (Illumina) platform. Differences in microbial composition were found between PSC and PSC+UC groups. The relative abundance of Veillonella and Megasphaera genera were increased depending on patients’ age at diagnosis. Veillonella was also increased in patients who were in an active status of the disease. Both genera were positively correlated to total bilirubin and gamma-glutamyl transferase. As a conclusion, the disease, the age and the disease activity status seem to influence the intestinal microbiome, highlighting the difference of intestinal microbiome profile for patients depending on age at diagnosis. We also showed an increase of Veillonella in patients with PSC and PSC+UC, and a positive correlation of dysbiosis and higher gamma-glutamyl transferase and total bilirubin in PSC+UC patients. Our findings are promising in the diagnosis, prognosis, and future therapeutic perspectives for PSC patients.

目前鲜有研究探讨原发性硬化性胆管炎（primary sclerosing cholangitis, PSC）与溃疡性结肠炎（ulcerative colitis, UC）患儿的肠道菌群组成及多样性之间的关联。本项横断面研究中，我们从某三级医院的小儿消化与肝病门诊招募了19岁以下的受试者，旨在分析合并或不合并UC的PSC患儿的肠道菌群特征。研究对象被分为PSC组、PSC+UC组及UC组。我们为每位受试者采集了粪便样本：其中患者组共30例，健康对照（健康亲属或邻居）共23例。采用MiSeq（Illumina）平台对菌群组成进行检测分析。研究结果显示，PSC组与PSC+UC组的微生物群落组成存在显著差异。韦荣球菌属（Veillonella）与巨球形菌属（Megasphaera）的相对丰度随患儿确诊时的年龄升高而增加。此外，韦荣球菌属在疾病活动期患者体内的丰度同样显著升高。上述两个菌属均与总胆红素及γ-谷氨酰转移酶水平呈正相关。综上，疾病类型、确诊时年龄及疾病活动状态均可对肠道菌群组成产生影响，凸显了确诊年龄对患儿肠道菌群谱的调控差异。本研究还发现，PSC组与PSC+UC组患者体内的韦荣球菌属丰度均显著升高；且在PSC+UC组患者中，菌群失调与更高水平的γ-谷氨酰转移酶及总胆红素呈正相关。本研究结果为PSC患者的临床诊断、预后评估及未来治疗策略开发提供了具有前景的参考依据。