The Roles Of Neuroendocrine Factors In Visceral Sensitivity And Gut Barrier Function Of Diarrhea-predominant Irritable Bowel Syndrome Patients

Part ? Analysis of Clinical symptoms and psychological status in diarrhea-predominant irritable bowel syndrome patientsAim:The present study was aimed to assess clinical symptoms and psychological status in diarrhea-predominant irritable bowel syndrome(IBS-D)patients,and to explore the role of psychological factors in IBS pathogenesis.Methods:This questionnaire-based study was conducted on 51 IBS-D patients referred to the Gastroenterology Department of the China-Japan Friendship Hospital from June 2015 to March 2016,together with 51 healthy controls.Clinical symptoms severity,life quality,anxiety and depression,visceral sensitivity index(VSI),sleep quality,stressful events and coping strategies were assessed by questionnaires.Results:All the patients and controls completed the assessments.Of the 51 patients,4 patients(7.8%)were mild IBS-D,36(70.6%)were moderate,and 11(21.6%)were severe.Compared to healthy controls,IBS-D patients had impaired life quality,higher scores in anxiety,depression and VSI,as well as poorer sleep quality.IBS-D patients experienced increased negative events in the last year,and tended to use negative coping styles.Correlation analyses in the patients showed that anxiety,depression,VSI,negative events and total score of life events were positively correlated with IBS severity.Conclusion:Our findings highlight a role of psychological factors in IBS-D pathophysiology.We believe that IBS-D is a psychosomatic disease triggered by psychosocial stress.Underlying the gastrointestinal symptoms may be the altered brain-gut interactions.Part ? Visceral sensitivity and gut barrier function in IBS-D patientsAim:The study aimed to evaluate visceral sensitivity and gut barrier function in diarrhea-predominant IBS(IBS-D)patients,and explore their roles in IBS-D pathophysiology.Methods:The study was conducted on 46 IBS-D patients referred to the Gastroenterology Department of the China-Japan Friendship Hospital from June 2015 to March 2016,together with 20 healthy controls.Clinical and psychological symptoms,visceral sensitivity to rectal balloon distention,and two serum intestinal barrier function markers d-lactate and diamine oxidase(DAO)were assessed.Results:Forty-six patients and 20 healthy controls completed the study.In visceral sensitivity test,maximum tolerable threshold was significantly decreased in IBS-D patients compared to controls.Serum DAO and d-lactate were significantly increased in IBS-D.Correlation analyses in patients showed that anxiety,visceral hypersensitivity and gut barrier impairment were positively correlated with IBS symptoms severity;anxiety,depression,and gut barrier impairment were associated with visceral hypersensitivity.Conclusion:IBS-D patients showed visceral hypersensitivity and impaired gut barrier function that were both associated with disease severity.These two factors may play vital roles in IBS-D pathophysiology.Part III Effects of neuroendocrine factors on visceral sensitivity and gut barrier function in patients with IBS-DAim:The aim of the study was to explore the neural-immune-endocrine network mechanism in irritable bowel syndrome(IBS)pathophysiology.Methods:The study was conducted on 38 diarrhea-predominant IBS(IBS-D)patients referred to the China-Japan Friendship Hospital from June 2015 to March 2016,together with 20 healthy controls.After clinical and psychological assessments,the subjects were tested for visceral sensitivity,serum NGF,and two gut barrier markers d-lactate and diamine oxidase(DAO).Rectosigmoid mucosal specimens were obtained under colonoscopy for NGF gene expression analysis,mast cell staining,and immunohistochemical staining of NGF,its receptor TrkA,and TRPV1-and CGRP-positive nerve fibres.We explored the associations of NGF expression with clinical and psychological features,visceral sensitivity,gut barrier function,and other experimental parameters in IBS-D patients.Results:All the patients and controls completed the study.Mucosal NGF mRNA expression,mast cell counts,TrkA and TRPV1 immunoreactivities were increased in IBS-D patients.In correlation analysis,NGF expression was positively correlated with the disease severity,anxiety and serum DAO,and was negatively correlated with visceral sensitivity thresholds.There were also positive associations of NGF mRNA expression with NGF and TRPV1 immunoreactivities.Conclusion:Our study adds new evidence that NGF may participate in IBS-D pathophysiology via mast cell-NGF-nerve interaction,contributing to abnormalities in visceral sensitivity and gut barrier function.These findings provide some clues for the elusive IBS-D pathophysiology,and for the search of more specific and effective therapeutic targets.