Alterations of the Subgingival Microbiota in Pediatric Crohn's Disease Studied Longitudinally in Discovery and Validation Cohorts.
Alterations of the Subgingival Microbiota in Pediatric Crohn's Disease Studied Longitudinally in Discovery and Validation Cohorts.
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DOI：
10.1097/mib.0000000000000557
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发表时间：
2015-12
影响因子：
4.9
通讯作者：
Bushman FD
中科院分区：
文献类型：
--
作者：
Kelsen J;Bittinger K;Pauly-Hubbard H;Posivak L;Grunberg S;Baldassano R;Lewis JD;Wu GD;Bushman FD
克罗恩病（CD）的口腔表现很常见。在这里，我们描述了儿童CD患者开始治疗和8周后的龈下微生物群，以确定与CD和治疗相关的微生物群落特征。儿童CD患者从宾夕法尼亚儿童医院招募。健康对照受试者从初级保健或骨科诊所招募。在治疗开始时和8周后收集龈下菌斑样本。治疗暴露包括5-ASA、免疫调节剂、类固醇和英夫利西单抗。通过16 S rRNA基因测序来表征微生物群。在单独的发现组（35例CD，43例健康）和验证组（43例CD，31例健康）中重复研究。两个队列中的大多数受试者在治疗8周后表现出临床应答（发现队列88%，验证队列79%）。在第0周，抗生素暴露和疾病状态都与细菌群落组成的差异有关。在发现队列中鉴定了17个属作为候选生物标志物，其中11个属在验证队列中得到确认。二氧化碳噬纤维菌、Rothia和TM 7在CD中相对于健康对照更丰富。其他细菌在CD受试者中随着抗生素暴露而大量减少。治疗8周后，与健康对照组相比，CD相关属未富集。龈下微生物群落结构与CD和抗生素使用不同。发现队列中的结果在单独的验证队列中重复。几种潜在的致病性细菌谱系与CD相关，但抗生素治疗并未大量减少，这表明需要进行额外监测。
Oral manifestations are common in Crohn's disease (CD). Here we characterized the subgingival microbiota in pediatric CD patients initiating therapy and after 8 weeks to identify microbial community features associated with CD and therapy. Pediatric CD patients were recruited from The Children's Hospital of Pennsylvania. Healthy control subjects were recruited from primary care or orthopedics clinic. Subgingival plaque samples were collected at initiation of therapy and after 8 weeks. Treatment exposures included 5-ASAs, immunomodualtors, steroids, and infliximab. The microbiota was characterized by 16S rRNA gene sequencing. The study was repeated in separate discovery (35 CD, 43 healthy) and validation cohorts (43 CD, 31 healthy). A majority of subjects in both cohorts demonstrated clinical response after 8 weeks of therapy (discovery cohort 88%, validation cohort 79%). At week 0, both antibiotic exposure and disease state were associated with differences in bacterial community composition. Seventeen genera were identified in the discovery cohort as candidate biomarkers, of which 11 were confirmed in the validation cohort. Capnocytophaga, Rothia, and TM7 were more abundant in CD relative to healthy controls. Other bacteria were reduced in abundance with antibiotic exposure among CD subjects. CD-associated genera were not enriched compared to healthy controls after 8 weeks of therapy. Subgingival microbial community structure differed with CD and antibiotic use. Results in the discovery cohort were replicated in a separate validation cohort. Several potentially pathogenic bacterial lineages were associated with CD but were not diminished in abundance by antibiotic treatment, suggesting targets for additional surveillance.