The Roles Of Fecal Metabolites In The Pathogenesis Of IBS-D

Part ? Analysis of clinical features and visceral sensitivity in IBS-D patientsBackground:Psychological status and visceral sensitivity play important roles in the pathogenesis of irritable bowel syndrome(IBS).However,studies extensively investigated the relationships between psychological factors,visceral sensitivity and clinical symptoms of IBS patients were very few and the results were inconsistent.Aim:To extensively assess the clinical symptoms,psychological characteristics and visceral sensitivity in IBS with predominant diarrhea(IBS-D)patients,and explore the roles of psychological status and visceral sensitivity in the pathogenesis of IBS-D.Methods:Thirty-seven IBS-D patients and nineteen controls were included.The psychological characteristics and clinical symptoms severity were evaluated by questionnaires.Visceral sensitivity was evaluated by Visceral Sensitivity Index(VSI)and was tested with anorectal high-resolution manometry.Results:The IBS-D patients presented increased anxious scores of Hospital Anxiety and Depression Scale(HADS)and Patient Health Scale 15(PHQ-15)compared with the controls on psychological aspect.Scores of Gastrointestinal Symptom Rating Scale(GSRS)and Bowel Disease Questionnaire(BDQ),which were used to assess clinical symptoms severity,significantly increased in IBS-D patients.Compared with the controls,IBS-D patients had higher VSI score,lower defecating sensation threshold and reduced maximum tolerable threshold.In the correlation analysis,GSRS score was correlated with the PHQ-15 score,and both of the anxious and depressive score of HADS.VSI score was correlated with IBS Symptom Severity Scale(IBS-SSS)score at the same time.Conclusion:IBS-D patients had psychological symptoms and visceral hypersensitivity,all of which may have important influence on clinical symptoms of IBS-D.Part ? The correlation between fecal metabolites and clinical features or visceral sensitivity in IBS-D patientsBackground:Fecal metabolites are correlated with visceral sensitivity,intestinal mucosal immune function and barrier function,all of which play critical parts in IBS pathogenesis.However,the role of metabolites in IBS pathophysiology is still unclear.Aim:To assess the fecal metabolite composition in IBS-D patients,and to explore its role in IBS-D pathophysiology.Methods:Thirty IBS-D patients and fifteen controls were included.Fecal metabolites,symptoms severity and visceral sensitivity were measured or assessed.Correlations between metabolites and visceral sensitivity or symptoms sensitivity were examined.Results:In fecal metabolites,levels of isohexanoate,His,Ala,Tyr,Phe,and Trp were significantly different between IBS-D patients and controls.In the correlation analysis,the levels of hexanoate,fumarate,pyruvate,Tyr and Val had a significant association with IBS-SSS score.Meanwhile,maximum tolerable threshold and BDQ score were correlated with isohexanoate and isovalerate.Conclusion:Altered profiles of fecal metabolites were correlated with symptom severity and visceral hypersensitivity in IBS-D patients.Fecal metabolites may be involved in the pathogenesis of IBS-D via visceral hypersensitivity.Part ? Effects of fecal metabolites on visceral sensitivity in patients with IBS-DBackground:fecal metabolites,especially isovalerate and isobutyrate,induced the release of 5-hydroxytryptamine(5-HT)from enterochromaffin cells and increased visceral sensitivity.Aim:To extensively assess the level of 5-HT in IBS-D patients,and to explore if fecal metabolites contribute to visceral hypersensitivity in patients with IBS-D via 5-HT.Methods:Thirty IBS-D patients and fifteen controls were included.Fecal metabolites and the levels of 5-HT in serum and intestinal mucosa were measured.Symptoms severity and visceral sensitivity were assessed.Results:Serum 5-HT level was elevated in IBS-D patients and was correlated with IBS-SSS score and VSI score.Intestinal mucosal 5-HT level increased in the IBS-D patients,but the difference did not reach statistical significance.Meanwhile,Serum 5-HT level was positively correlated with the levels of isohexanoate and isovalerate in faeces.Conclusion:Elevated 5-HT in IBS-D patients was related to fecal metabolites,symptom severity and visceral hypersensitivity.These findings provide new evidence that fecal metabolites may contribute to visceral hypersensitivity in IBS-D via 5-HT.