Small intestinal mucosal transcriptomics in IBS. Small intestinal mucosal transcriptomics in IBS

Irritable bowel syndrome (IBS) patients often experience meal associated symptoms. Our objective was to determine small intestinal mechanisms of lipid-induced symptoms and rectal hypersensitivity in IBS based on RNA-seq. Overall design: We recruited 26 IBS patients (12 IBS-C, 14 IBS-D) and 15 healthy volunteers (HV). In vivo permeability was assessed using saccharide excretion assay. Rectal sensitivity was assessed before and after a 1-hour small bowel lipid infusion (2 mL/min) and symptoms assessed throughout. Next, an extended upper endoscopy with probe-based confocal laser endomicroscopy (pCLE) was performed with changes assessed following application of intraluminal lipids. Mucosal biopsies from duodenum and jejunum were obtained for bulk RNA sequencing (RNA-seq). After library size selection of RNA-seq data, 11, 10, 12 Duodenum samples for HV, IBS-C and IBS-D were kept, and 12, 7, 8 Jejunum samples for HV, IBS-C and IBS-D were kept for further analysis.

肠易激综合征（Irritable bowel syndrome, IBS）患者常出现与进餐相关的症状。本研究旨在基于RNA测序（RNA-seq），明确肠易激综合征患者中脂质诱导症状与直肠高敏感性的小肠致病机制。实验设计：我们招募了26名肠易激综合征患者（12例便秘型肠易激综合征（IBS-C）、14例腹泻型肠易激综合征（IBS-D））以及15名健康志愿者（healthy volunteers, HV）。首先通过糖类排泄试验评估受试者的体内肠通透性；分别在1小时小肠脂质输注（流速2 mL/min）前后检测直肠敏感性，并全程记录受试者的相关症状。随后，我们开展了搭载探头式共聚焦激光内镜（probe-based confocal laser endomicroscopy, pCLE）的扩展上消化道内镜检查，并评估管腔内脂质给药后的黏膜组织变化。同时采集十二指肠与空肠的黏膜活检标本，用于批量RNA测序（RNA-seq）。对RNA-seq数据进行文库片段大小筛选后，最终保留的有效样本为：健康志愿者、便秘型肠易激综合征、腹泻型肠易激综合征组的十二指肠样本分别为11、10、12例；三组的空肠样本则分别为12、7、8例，用于后续分析。