The Role Of Leptin,Psychological Factors And Visceral Sensitivity In The Pathogenesis Of Diarrhea-predominant Irritable Bowel Syndrome

Part I Analysis of clinical symptoms,psychological status,visceral sensitivity and autonomic nerve function of diarrhea-predominant irritable bowel syndrome(IBS-D)patients.Aim:The purpose of the analysis was to evaluate the performance of indicators of diarrhea-predominant irritable bowel syndrome including psychological status,symptoms,sensitivity,and autonomic function.Methods:We recruited 56 IBS-D patients fulfilling the Rome III criteria and 42 age-and sex-matched healthy controls.From January to July 2016,all the patients went to the Gastroenterology Department of the Sino-Japanese Friendship Hospital for treatment.Controls were recruited through public advertisement or from asymptomatic patients undergoing colonoscopy for colorectal cancer screening or polyposis follow-up.Clinical symptoms severity,at the same time,the patient’s mental health,visceral sensitivity,neurological function,and actual symptoms were examined.Results:In the analysis case,there were 5 cases of moderate to mild IBS(8.9%),40 cases of moderate IBS(71.4%),and 11 cases of severe IBS(19.6%).Compared with the healthy control group,there was a significant decrease in the quality of life of the disease group,and there was a significant increase in anxiety and depression scores.The disease group was significantly lower in terms of initial sensory threshold,continuous defecation threshold,and maximum tolerance threshold for rectal distension stimulation.At the same time,both the autonomic nerve function score and the parasympathetic score were significantly higher,and the abnormal ratio between the two was also significantly higher.In IBS-D group,the scores of psychological questionnaires were positively correlated with clinical symptoms severity,while the first sensation threshold,defecating sensation threshold,and maximum tolerable threshold were negatively correlated with clinical symptoms severity.There is no obvious link between ANF and the rest of the parameters.Conclusion:Patients in the study had psychoneurotic abnormalities,high visceral hypersensitivity,and parasympathetic disorders as core autonomic dysregulation phenomena.At the same time,mental and psychological conditions and visceral sensitivities all had a significant impact on the condition,or in the overall The pathogenesis constitutes a significant influence.Part Ⅱ The role of leptin in the pathogenesis of diarrhea-predominant irritable bowel syndromeBackground and aim:The pathogenesis of IBS-D is complex.Recent studies of the pathophysiology of IBS-D have focused on molecular mechanisms.Some studies suggested that the levels leptin altered in IBS-D patients.As a member of the brain-gut peptides,leptin not only exerts significant biological effects,such as appetite control,by signaling satiety and increasing energy expenditure,but also through modulation of the immune system and gastrointestinal function.The study aimed to measure leptin levels and analyze the relationship of leptin with clinical features,visceral sensitivity,mast cells and nerve fibers.Methods:Forty-two patients with diarrhea-predominant IBS fulfilling the Rome III criteria and 20 age-and sex-matched healthy controls underwent a clinical and psychological evaluation using validated questionnaires,along with colonoscopy,colonic mucosal biopsy,and visceral sensitivity testing.Serum leptin levels were assayed using enzyme-linked immunosorbent assay.Mucosal leptin expression and localization were evaluated using immunohistochemistry and immunofluorescence.Mucosal leptin mRNA levels were quantified using quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR).Mast cell counts and activation rates were investigated with toluidine blue staining.Correlation analyses between these parameters were performed.Results:The paper relies on 42 patients and 20 healthy controls to achieve this study.IBS-D patients had significantly lower first sensation threshold,defecation sensation threshold and maximum tolerable threshold,and their mucosal leptin expression,leptin mRNA levels and mast cell activation rates were significantly increased.The colocalization of leptin and leptin receptors was observed on mast cells and PGP9.5-positive nerve fibers in the intestinal mucosa.Also,leptin expression was positively correlated with anxiety,depression,and the mast cell activation rate,but negatively correlated with the defecation sensation threshold and the maximum tolerance threshold during visceral sensitivity testing.Conclusion:Increased levels of mucosal leptin,may interact with mast cells and nervous system contributing to the pathogenesis of IBS-D.These findings provide some clues for the elusive IBS-D pathophysiology,at the same time,explore more specific and efficient treatment goals.