Gastroenterology Department, Children's Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.
mSystems. 2024 Sep 17;9(9):e0078324. doi: 10.1128/msystems.00783-24. Epub 2024 Aug 16.
Gut dysbiosis is closely related to dysregulated microRNAs (miRNAs) in the intestinal epithelial cells, which plays an important role in the pathogenesis of Crohn's disease (CD). We investigated the relationship between fecal gut microbiome (GM) and intestinal tissue miRNAs in different stages of pediatric CD. Metagenomic analysis and miRNA sequencing were conducted to examine the GM and intestinal miRNA profiles of CD patients before and after clinical induction therapy and the controls. Twenty-seven newly diagnosed, therapy-naïve pediatric patients with active CD and 11 non-inflammatory bowel disease (IBD) controls were recruited in this study. Among CD patients, 11 patients completed induction treatment and reached clinical remission. Both GM and miRNA profiles were significantly changed between CD patients and controls. Seven key bacteria were identified at species level including , , , sp. AGR2135, , , and , the exact proportions of which were further validated by real-time quantitative PCR analysis. Eight key miRNAs were also identified including hsa-miR-215-5p, hsa-miR-194-5p, hsa-miR-12135, hsa-miR-509-3-5p, hsa-miR-212-5p, hsa-miR-4448, hsa-miR-501-3p, and hsa-miR-503-5p. The functional enrichment analysis of differential miRNAs indicated the significantly altered cyclin protein, cyclin-dependent protein, and cell cycle pathway. The close interactions between seven key bacteria and eight key miRNAs were further investigated by miRNA target prediction. The association between specific miRNA expressions and key gut bacteria at different stages of CD supported their important roles as potential molecular biomarkers. Understanding the relationship between them will help us to explore the molecular mechanisms of CD.
Since previous studies have focused on the change of the fecal gut microbiome and intestinal tissue miRNA in pediatric Crohn's disease (CD), the relationship between them in different stages is still not clear. This is the first study to explore the gut microbiota and miRNA and their correlations with the Pediatric Crohn's Disease Activity Index (PCDAI). Crohn's Disease Endoscopic Index of Severity (CDEIS), and calprotectin, by applying two omics approach in three different groups (active CD, CD in remission with exclusive enteral nutrition or infliximab induction therapy, and the healthy controls). Both gut microbiome structure and the miRNA profiles were significantly changed in the different stage of CD. Seven key gut microbiome at species and eight key miRNAs were found, and their close interactions were further fully investigated by miRNA target prediction.
肠道微生物群落失调与肠上皮细胞中调控失常的 microRNAs（miRNAs）密切相关，其在克罗恩病（CD）的发病机制中发挥重要作用。本研究旨在探讨不同疾病阶段儿童 CD 患者粪便肠道微生物群（GM）与肠道组织 miRNAs 之间的关系。
本研究纳入了 27 例新诊断、未经治疗的活动期 CD 患儿和 11 例非炎症性肠病（IBD）对照者。对 CD 患者进行宏基因组分析和 miRNA 测序，以检测 CD 患者在临床诱导治疗前后及对照者的 GM 和肠道 miRNA 谱。其中 11 例 CD 患者完成诱导治疗并达到临床缓解。
CD 患者与对照者的 GM 和 miRNA 谱均发生显著变化。在物种水平上鉴定出 7 种关键细菌，包括 、 、 、 、 、 、 、 sp. AGR2135，通过实时定量 PCR 分析进一步验证了其确切比例。还鉴定出 8 种关键 miRNAs，包括 hsa-miR-215-5p、hsa-miR-194-5p、hsa-miR-12135、hsa-miR-509-3-5p、hsa-miR-212-5p、hsa-miR-4448、hsa-miR-501-3p 和 hsa-miR-503-5p。差异 miRNAs 的功能富集分析表明，细胞周期蛋白、细胞周期蛋白依赖性蛋白和细胞周期途径发生明显改变。通过 miRNA 靶标预测进一步研究了 7 种关键细菌和 8 种关键 miRNAs 之间的密切相互作用。不同阶段 CD 患者特定 miRNA 表达与关键肠道细菌之间的关联支持它们作为潜在分子生物标志物的重要作用。
了解它们之间的关系将有助于我们探索 CD 的分子机制。
由于先前的研究集中在儿科 CD 中粪便肠道微生物群和肠道组织 miRNA 的变化，因此它们在不同阶段之间的关系仍不清楚。这是第一项通过两种组学方法在三个不同组（活动期 CD、接受肠内营养或英夫利昔单抗诱导治疗缓解的 CD 以及健康对照者）中探索肠道微生物组和 miRNA 及其与儿科 CD 活动指数（PCDAI）、克罗恩病内镜指数严重程度（CDEIS）和钙卫蛋白的关系的研究。CD 的不同阶段肠道微生物群落结构和 miRNA 谱均发生显著变化。发现了 7 种关键肠道微生物（属）和 8 种关键 miRNAs，并通过 miRNA 靶标预测进一步全面研究了它们的密切相互作用。
