Table_5_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.

目前针对伴或不伴溃疡性结肠炎（ulcerative colitis, UC）的原发性硬化性胆管炎（primary sclerosing cholangitis, PSC）患儿肠道菌群组成与多样性的相关研究较为匮乏。本项横断面研究中，我们从某三级医院儿科消化与肝病门诊招募了19岁以下的受试者，旨在明确不同分组患儿的肠道菌群特征。受试者按确诊疾病类型分为三组：原发性硬化性胆管炎组（PSC组）、合并溃疡性结肠炎的原发性硬化性胆管炎组（PSC+UC组）以及溃疡性结肠炎组（UC组）。我们为所有受试患儿（n=30）及其健康亲属/邻居（n=23）采集了粪便样本，采用Illumina MiSeq测序平台对菌群组成进行分析。研究发现，PSC组与PSC+UC组的菌群组成存在显著差异。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；其中韦荣球菌属在疾病活动期患儿体内的丰度同样显著升高。上述两个菌属的相对丰度均与总胆红素及γ-谷氨酰转移酶（gamma-glutamyl transferase）水平呈正相关。综上，疾病类型、确诊年龄及疾病活动状态均可对肠道菌群组成产生影响，提示患儿确诊时的年龄会显著影响其肠道菌群谱特征。本研究还发现，PSC组与PSC+UC组患儿体内的韦荣球菌属丰度均升高，且在PSC+UC组患儿中，菌群失调（dysbiosis）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患儿的临床诊断、预后评估及未来治疗方案开发提供了颇具前景的参考依据。