Twin Study Indicates Loss of Interaction Between Microbiota and Mucosa of Patients With Ulcerative Colitis
Twin Study Indicates Loss of Interaction Between Microbiota and Mucosa of Patients With Ulcerative Colitis
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DOI：
10.1053/j.gastro.2011.04.011
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发表时间：
2011-07-01
期刊：
影响因子：
29.4
通讯作者：
Schreiber, Stefan
中科院分区：
文献类型：
--
作者：
Lepage, Patricia;Haesler, Robert;Schreiber, Stefan
背景与目的：遗传和环境因素之间的相互作用被认为参与了炎症性肠病的发病和启动。我们分析了溃疡性结肠炎（UC）不一致的双胞胎对胃肠道粘膜微生物群和宿主基因之间的相互作用，以研究微生物群和粘膜上皮之间的功能相互作用。方法：收集UC患者及其健康双胞胎（不一致双胞胎对）和无UC双胞胎的乙状结肠活检。通过16 S核糖体DNA文库分析确定微生物群谱;通过微阵列分析确定信使RNA谱。研究结果：UC患者的微生物群失调，其特征是细菌多样性较少，放线菌和变形菌比他们的健康兄弟姐妹更多;来自不和谐双胞胎的健康兄弟姐妹比健康双胞胎有更多来自毛螺菌科和瘤胃球菌科的细菌。在健康的双胞胎中，34个粘膜转录物与细菌属相关，而健康个体和UC双胞胎中分别只有25个和11个与细菌属相关。与氧化和免疫反应相关的转录本在UC患者和他们的健康双胞胎之间差异表达。结论：粘膜的转录谱似乎与结肠微生物群相互作用;这种相互作用似乎在UC患者的结肠中丢失。细菌的功能，如丁酸的产生，可能会影响粘膜基因的表达。UC患者的基因表达谱不同，生物多样性水平低于健康双胞胎，以及不寻常的需氧菌。UC患者的潜在保护性细菌种类的百分比低于他们的健康双胞胎。
BACKGROUND & AIMS: Interactions between genetic and environmental factors are believed to be involved in onset and initiation of inflammatory bowel disease. We analyzed the interaction between gastrointestinal mucosal microbiota and host genes in twin pairs discordant for ulcerative colitis (UC) to study the functional interaction between microbiota and mucosal epithelium. METHODS: Biopsy were collected from sigmoid colon of UC patients and their healthy twins (discordant twin pairs) and from twins without UC. Microbiota profiles were determined from analysis of 16S ribosomal DNA libraries; messenger RNA profiles were determined by microarray analysis. RESULTS: Patients with UC had dysbiotic microbiota, characterized by less bacterial diversity and more Actinobacteria and Proteobacteria than that of their healthy siblings; healthy siblings from discordant twins had more bacteria from the Lachnospiraceae and Ruminococcaceae families than twins who were both healthy. In twins who were both healthy, 34 mucosal transcripts correlated with bacterial genera, whereas only 25 and 11 correlated with bacteria genera in healthy individuals and their twins with UC, respectively. Transcripts related to oxidative and immune responses were differentially expressed between patients with UC and their healthy twins. CONCLUSIONS: The transcriptional profile of the mucosa appears to interact with the colonic microbiota; this interaction appears to be lost in colon of patients with UC. Bacterial functions, such as butyrate production, might affect mucosal gene expression. Patients with UC had different gene expression profiles and lower levels of biodiversity than their healthy twins, as well as unusual aerobic bacteria. Patients with UC had lower percentages of potentially protective bacterial species than their healthy twins.