Altered profiles of fecal metabolites correlate with visceral hypersensitivity and may contribute to symptom severity of diarrhea-predominant irritable bowel syndrome  

作　　者：Wen-Xue Zhang Yu Zhang Geng Qin Kai-Min Li Wei Wei Su-Yun Li Shu-Kun Yao 

机构地区：[1]Graduate School,Peking Union Medical College and Chinese Academy of Medical Sciences,Beijing 100730,China [2]Department of Gastroenterology,China-Japan Friendship Hospital,Beijing 100029,China [3]School of Biological Science and Medical Engineering,Beihang University,Beijing 100191,China [4]Department of Epidemiology and Health Statistics,School of Public Health,Qingdao University,Qingdao 266071,Shandong Province,China

出　　处：《World Journal of Gastroenterology》2019年第43期6416-6429,共14页世界胃肠病学杂志（英文版）

基　　金：the National Key Technology Support Program for the “12th Five-Year Plan” of China,No.2014BAI08B00;the Research Projects on Biomedical Transformation of China-Japan Friendship Hospital,No.PYBZ1815

摘　　要：BACKGROUND Fecal metabolites are associated with gut visceral sensitivity,mucosal immune function and intestinal barrier function,all of which have critical roles in the pathogenesis of irritable bowel syndrome(IBS).However,the metabolic profile and pathophysiology of IBS are still unclear.We hypothesized that altered profiles of fecal metabolites might be involved in the pathogenesis of IBS with predominant diarrhea(IBS-D).AIM To investigate the fecal metabolite composition and the role of metabolites in IBSD pathophysiology.METHODS Thirty IBS-D patients and 15 age-and sex-matched healthy controls(HCs)underwent clinical and psychological assessments,including the IBS Symptom Severity System(IBS-SSS),an Italian modified version of the Bowel Disease Questionnaire,the Bristol Stool Form Scale(BSFS),the Hospital Anxiety and Depression Scale,and the Visceral Sensitivity Index.Visceral sensitivity to rectal distension was tested using high-resolution manometry system by the same investigator.Fecal metabolites,including amino acids and organic acids,were measured by targeted metabolomics approaches.Correlation analyses between these parameters were performed.RESULTS The patients presented with increased stool water content,more psychological symptoms and increased visceral hypersensitivity compared with the controls.In fecal metabolites,His[IBS-D:0.0642(0.0388,0.1484),HC:0.2636(0.0780,0.3966),P=0.012],Ala[IBS-D:0.5095(0.2826,0.9183),HC:1.0118(0.6135,1.4335),P=0.041],Tyr[IBS-D:0.1024(0.0173,0.4527),HC:0.5665(0.2436,1.3447),P=0.018],Phe[IBS-D:0.1511(0.0775,0.3248),HC:0.3967(0.1388,0.7550),P=0.028],and Trp[IBS-D:0.0323(0.0001,0.0826),HC:0.0834(0.0170,0.1759),P=0.046]were decreased in IBS-D patients,but isohexanoate[IBS-D:0.0127(0.0060,0.0246),HC:0.0070(0.0023,0.0106),P=0.028]was significantly increased.Only Tyr was mildly correlated with BSFS scores in all subjects(r=-0.347,P=0.019).A possible potential biomarker panel was identified to correlate with IBS-SSS score(R2 Adjusted=0.693,P<0.001).In this regression model,the lBACKGROUND Fecal metabolites are associated with gut visceral sensitivity, mucosal immune function and intestinal barrier function, all of which have critical roles in the pathogenesis of irritable bowel syndrome(IBS). However, the metabolic profile and pathophysiology of IBS are still unclear. We hypothesized that altered profiles of fecal metabolites might be involved in the pathogenesis of IBS with predominant diarrhea(IBS-D).AIM To investigate the fecal metabolite composition and the role of metabolites in IBSD pathophysiology.METHODS Thirty IBS-D patients and 15 age-and sex-matched healthy controls(HCs)underwent clinical and psychological assessments, including the IBS Symptom Severity System(IBS-SSS), an Italian modified version of the Bowel Disease Questionnaire, the Bristol Stool Form Scale(BSFS), the Hospital Anxiety and Depression Scale, and the Visceral Sensitivity Index. Visceral sensitivity to rectal distension was tested using high-resolution manometry system by the same investigator. Fecal metabolites, including amino acids and organic acids, weremeasured by targeted metabolomics approaches. Correlation analyses between these parameters were performed.RESULTS The patients presented with increased stool water content, more psychological symptoms and increased visceral hypersensitivity compared with the controls. In fecal metabolites, His [IBS-D: 0.0642(0.0388, 0.1484), HC: 0.2636(0.0780, 0.3966), P= 0.012], Ala [IBS-D: 0.5095(0.2826, 0.9183), HC: 1.0118(0.6135, 1.4335), P = 0.041],Tyr [IBS-D: 0.1024(0.0173, 0.4527), HC: 0.5665(0.2436, 1.3447), P = 0.018], Phe[IBS-D: 0.1511(0.0775, 0.3248), HC: 0.3967(0.1388, 0.7550), P = 0.028], and Trp[IBS-D: 0.0323(0.0001, 0.0826), HC: 0.0834(0.0170, 0.1759), P = 0.046] were decreased in IBS-D patients, but isohexanoate [IBS-D: 0.0127(0.0060, 0.0246), HC:0.0070(0.0023, 0.0106), P = 0.028] was significantly increased. Only Tyr was mildly correlated with BSFS scores in all subjects(r =-0.347, P = 0.019). A possible potential biomarker panel was identified to correla

关 键 词：FECAL metabolite IRRITABLE bowel syndrome Amino ACIDS Organic ACIDS Short chain fatty ACIDS VISCERAL HYPERSENSITIVITY 

分 类 号：R57[医药卫生—消化系统]