Abstract：
OBJECTIVE: 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.
METHODS: Fifty-one Rome III Campylobacter 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.
RESULTS: 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; P = .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 N-acetylputrescine was increased in PI-IBS and associated with colonic permeability, worse diarrhea, and negatively correlated with abundance of Collinsella aerofaciens. Histamine and N-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).
CONCLUSIONS: Campylobacter PI-IBS patients demonstrate higher colonic permeability, which associated with changes in polyamine and histamine metabolites. Female patients demonstrated greater molecular changes.
METHODS: Fifty-one Rome III Campylobacter 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.
RESULTS: 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; P = .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 N-acetylputrescine was increased in PI-IBS and associated with colonic permeability, worse diarrhea, and negatively correlated with abundance of Collinsella aerofaciens. Histamine and N-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).
CONCLUSIONS: Campylobacter PI-IBS patients demonstrate higher colonic permeability, which associated with changes in polyamine and histamine metabolites. Female patients demonstrated greater molecular changes.
摘要：
目的：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，它的生理和分子特征没有得到很好的研究。我们的目的是确定生理表型，结肠转录组，粪便微生物组，和PI-IBS中的代谢组。
方法：纳入51例罗马III弯曲杆菌PI-IBS患者和39例健康志愿者（HV）。参与者填写了问卷，体内肠道通透性，胃肠运输,和直肠感觉.收集粪便样本用于鸟枪宏基因组学，非靶向代谢组学，和大量RNAseq的乙状结肠活检。差异基因表达，确定了微生物群组成和代谢物丰度的差异。通过加权基因相关网络分析并确定与临床和生理参数的相关性来鉴定基因和代谢物簇。
结果：PI-IBS（59%F，46±2年。)和HV(64%F，42±2年。)人口统计数据具有可比性。平均IBS症状严重程度评分为227分；94％为非便秘。PI-IBS中2-24h乳果糖排泄增加，提示结肠通透性增加（4.4±0.5mgvs.2.6±0.3mg,p=0.01)。两组之间的结肠运输和感觉阈值相似。总的来说,2036个粘膜基因和223个粪便代谢物的表达不同，女性的变化更加突出。粪便N-乙酰腐胺在PI-IBS中增加，并与结肠通透性相关，更严重的腹泻,并与Collinsellaaerofaciens的丰度呈负相关。组胺和N-乙酰组胺与2-24小时乳果糖排泄呈正相关。八个加权基因共表达模块与表型显著相关(性别，大便频率,结肠通透性,transit).
结论：弯曲杆菌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。
方法：纳入51例罗马III弯曲杆菌PI-IBS患者和39例健康志愿者（HV）。参与者填写了问卷，体内肠道通透性，胃肠运输,和直肠感觉.收集粪便样本用于鸟枪宏基因组学，非靶向代谢组学，和大量RNAseq的乙状结肠活检。差异基因表达，确定了微生物群组成和代谢物丰度的差异。通过加权基因相关网络分析并确定与临床和生理参数的相关性来鉴定基因和代谢物簇。
结果：PI-IBS（59%F，46±2年。)和HV(64%F，42±2年。)人口统计数据具有可比性。平均IBS症状严重程度评分为227分；94％为非便秘。PI-IBS中2-24h乳果糖排泄增加，提示结肠通透性增加（4.4±0.5mgvs.2.6±0.3mg,p=0.01)。两组之间的结肠运输和感觉阈值相似。总的来说,2036个粘膜基因和223个粪便代谢物的表达不同，女性的变化更加突出。粪便N-乙酰腐胺在PI-IBS中增加，并与结肠通透性相关，更严重的腹泻,并与Collinsellaaerofaciens的丰度呈负相关。组胺和N-乙酰组胺与2-24小时乳果糖排泄呈正相关。八个加权基因共表达模块与表型显著相关(性别，大便频率,结肠通透性,transit).
结论：弯曲杆菌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。
