Characterization of the Mucosally-Adherent Duodenal Microbiome in Children with and without Crohn's Disease.

Characterization of the Mucosally-Adherent Duodenal Microbiome in Children with and without Crohn's Disease.
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克罗恩病患儿和非克罗恩病患儿的粘膜粘附性十二指肠微生物组特征

DOI:
10.3390/ph15070850
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发表时间:
2022-07-11
期刊:
Pharmaceuticals (Basel, Switzerland)
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其他
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操纵微生物组是炎症性肠病(IBD)的合理治疗策略。与结肠和末端回肠(TI)相比,对十二指肠中微生物组成的了解很少。这种知识上的差距对于克罗恩病(CD)儿童尤其重要,因为儿童十二指肠CD的患病率高于成人。我们的目的是表征患有和不患有CD的儿童的粘膜粘附十二指肠微生物组的细菌组成,作为在该疾病部位开发靶向IBD治疗策略的第一步。新鲜冷冻的粘膜活检标本取自初治CD儿童和年龄和性别匹配的对照组的十二指肠和TI。分析提取的DNA的16 S核糖体RNA细菌基因区V4(Novogene; Beijing,China)中的序列变异。比较了来自对照组和有和无慢性活动性炎症的CD组的十二指肠和TI样本的细菌相对丰度、α和β组成以及多样性(总共来自73名儿童的118个样本;大约100个样本)。50%CD),使用UniFrac相异度系数(α < 0.05)、线性判别分析效应大小(LEfSe)分析(LDA评分≥ 2)和具有算术平均值的未加权配对组方法(UPGMA)分析。评估细菌丰度、性别、年龄、合并用药和绒毛长度之间的关系。在对照人群(R值= 0.558,p = 0.001)和活动性CD儿童(R值= 0.301,p = 0.001)中,十二指肠中的微生物组成与TI存在显著差异。在对照组和CD α组之间观察到细菌丰度的显著差异(LDA > 4)。没有CD的儿童的十二指肠的特征在于伪单胞菌目的丰度增加,而CD中活跃发炎的十二指肠的特征在于拟杆菌目的丰度增加,特别是普雷沃氏菌科。这一趋势与先前发表的TI中微生物组成的观察结果相反,其中活动性炎症与拟杆菌属丰度的相对减少和变形菌属(包括假单胞菌目)的增加相关。丰度与年龄、性别、合并用药或绒毛长度之间无统计学显著相关性,但拟杆菌除外,其在TI中的丰度随年龄显著降低(p = 0.048)。儿科十二指肠微生物组与TI不同,其特征在于健康儿童中假单胞菌和螺旋体丰度增加,活动性CD患者中类杆菌丰度增加。
Manipulation of the microbiome is a rational treatment strategy for inflammatory bowel disease (IBD). Compared to the colon and terminal ileum (TI), understanding of the microbial composition in the duodenum is sparse. This gap in knowledge is especially significant for children with Crohn’s disease (CD) because the prevalence of duodenal CD is higher in children than in adults. Our aim was to characterize the bacterial composition of the mucosally-adherent duodenal microbiome in children with and without CD as a first step toward development of targeted IBD treatment strategies at this disease location. Fresh-frozen mucosal biopsies were obtained from the duodenum and TI of children with treatment-naïve CD and age- and sex-matched controls. Extracted DNA was analyzed for sequence variation in the 16S ribosomal RNA bacterial gene region V4 (Novogene; Beijing, China). Bacterial relative abundance, alpha and beta composition, and diversity, were compared across duodenal and TI samples from the controls and CD groups with and without chronic active inflammation (118 samples from 73 children total; approx. 50% CD), using UniFrac dissimilarity coefficients (α < 0.05), Linear Discriminant Analysis Effect Size (LEfSe) analysis (LDA score ≥ 2), and Unweighted Pair Group Method with Arithmetic Mean (UPGMA) analysis. The relationships between bacterial abundance, sex, age, concomitant medication use, and villous length were assessed. The microbial composition in the duodenum was significantly different from the TI in the control population(R-value = 0.558, p = 0.001) and in children with active CD (R-value = 0.301, p = 0.001). Significant differences in bacterial abundance were noted between the control and CD duodena (LDA > 4). The duodenum of children without CD was characterized by increased abundance in Pseudomonodales, whereas the actively inflamed duodenum in CD was characterized by increased abundance of Bacteroidales, specifically the family Prevotellaceae. This trend is opposite of previously published observations of microbial composition in the TI, where active inflammation was associated with a relative decrease in the abundance of Bacteroidetes and an increase in Proteobacteria, including Pseudomonadales. No statistically significant correlations were noted between abundance and age, sex, concomitant medication use or villous length, except for Bacteroidetes, which significantly decreased in abundance in the TI with age (p = 0.048). The pediatric duodenal microbiome is distinct from the TI and characterized by an increased abundance of Pseudomonodales and Spirochetes in healthy children, and an increased abundance of Bacteroidales in active CD patients.
DOI: 10.1186/1471-230x-13-113
发表时间: 2013-07-11
影响因子: 2.4
作者:
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影响因子: --
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