Postinfection irritable bowel syndrome (PI-IBS) is well-known epidemiologically; however, its physiological and molecular characteristics are not well studied. We aimed to determine the physiological phenotypes, colonic transcriptome, fecal microbiome, and metabolome in PI-IBS. Fifty-one Rome III PI-IBS patients and 39 healthy volunteers (HV) were enrolled. Participants completed questionnaires, in vivo intestinal permeability, gastrointestinal transit, and rectal sensation. Fecal samples were collected for shotgun metagenomics, untargeted metabolomics, and sigmoid colonic biopsies for bulk RNAseq. Differential gene expression, differences in microbiota composition, and metabolite abundance were determined. Gene and metabolite clusters were identified via weighted gene correlation network analysis and correlations with clinical and physiological parameters determined. PI-IBS (59% female; 46 ± 2 years) and HV (64% female; 42 ± 2 years) demographics were comparable. Mean IBS-symptom severity score was 227; 94% were nonconstipation. Two- to 24-hour lactulose excretion was increased in PI-IBS, suggesting increased colonic permeability (4.4 ± 0.5 mg vs 2.6 ± 0.3 mg; = .01). Colonic transit and sensory thresholds were similar between the 2 groups. Overall, expression of 2036 mucosal genes and 223 fecal metabolites were different, with changes more prominent in females. Fecal -acetylputrescine was increased in PI-IBS and associated with colonic permeability, worse diarrhea, and negatively correlated with abundance of . Histamine and -acetylhistamine positively associated with 2- to 24-hour lactulose excretion. Eight weighted gene coexpression modules significantly correlated with phenotypes (sex, stool frequency, colonic permeability, transit). PI-IBS patients demonstrate higher colonic permeability, which associated with changes in polyamine and histamine metabolites. Female patients demonstrated greater molecular changes.

中文翻译：

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感染后肠易激综合征结肠通透性增加的转录组学和代谢组学相关性


感染后肠易激综合征 （PI-IBS） 在流行病学上是众所周知的;然而，其生理和分子特性尚未得到很好的研究。我们旨在确定 PI-IBS 中的生理表型、结肠转录组、粪便微生物组和代谢组。纳入了 51 例罗马 III PI-IBS 患者和 39 例健康志愿者 （HV）。参与者完成了问卷、体内肠道通透性、胃肠道转运和直肠感觉。收集粪便样本用于鸟枪法宏基因组学、非靶向代谢组学和 S 形结肠活检用于大量 RNAseq。测定差异基因表达、微生物群组成的差异和代谢物丰度。通过加权基因相关网络分析鉴定基因和代谢物簇，并确定与临床和生理参数的相关性。PI-IBS（59% 为女性;46 ± 2 岁）和 HV（64% 为女性;42 ± 2 岁）人口统计数据具有可比性。平均 IBS 症状严重程度评分为 227;94% 是非便秘。PI-IBS 中 2 至 24 小时的乳果糖排泄增加，表明结肠通透性增加 （4.4 ± 0.5 mg vs 2.6 ± 0.3 mg;= .01）。两组之间的结肠传输和感觉阈值相似。总体而言，2036 个粘膜基因和 223 个粪便代谢物的表达存在差异，其中女性的变化更为明显。粪便乙酰腐胺在 PI-IBS 中增加，与结肠通透性、更严重的腹泻相关，并与 .组胺和 - 乙酰组胺与 2 至 24 小时乳果糖排泄呈正相关。8 个加权基因共表达模块与表型 （性别、大便频率、结肠通透性、传输） 显著相关。 PI-IBS 患者表现出较高的结肠通透性，这与多胺和组胺代谢物的变化有关。女性患者表现出更大的分子变化。