| Background and Objective Irritable bowel syndrome (IBS) was currently viewed as a common functional bowel disorder which presented with abdominal pain/discomfort as characteristic symptom, and mostly associated with altered bowel habits and stool forms. IBS with diarrhea (IBS-D) is the most common subgroup in clinical practice in China. The frequency and severity of symptoms among IBS-D patients are arbitrary, they varied with the time, including alternation with onset and remission, or persistence for long time. Recurrent or obscure symptoms impair the patient’s quality of life. The regularity and pathophysiological mechanisms for the symptom onset or persistence were unclear. The aims of this study were (1) to investigate the natural regularity of the symptoms in patients with IBS-D;(2) to understand the relationships of colonic motility and brain activities in IBS-D patients with symptom onset, remission and persistence;(3) to explore the roles of colonic mucosal enterochromaffin cell (EC) and mast cell (MC) in the symptom onset or persistence of IBS-D.Material and Methods Consecutive IBS-D patients met the Rome III criteria and excluded out the diagnosis of organic diseases were enrolled in this study. Hamilton rating scale for anxiety/depression (HAMA/HAMD) and IBS specific quality of life (IBS-QOL) were applied to evaluate their psychological status and the quality of life. A part of patients with typical IBS-D symptoms underwent the examination of colon manometry and brain functional magnetic resonance imaging (fMRI) during period of onset, remission and persistence, and the healthy subjects were designed as the control group. The biopsy samples were obtained during colonoscopy examination from sigmoid colon for detection of EC cells and mast cells by immunohistochemistry stainings with5-HT or mast cell tryptase. The number of the positive staining cells and degranulated mast cells were counted by an independent pathologist.We subtyped the symptoms status according to the followings:onset indicates the patients having typical IBS-D symptoms in the three days; remission indicates patients having no any IBS symptoms over ten days; persistent indicates the patients having IBS-D symptoms more than2/3of the days during the past three months. Results A total of351patients completed the questionnaire survey, the symptoms episodic frequency was between2day/months～1day/week in95patients (onset group), daily symptoms in94cases (persistent group), symptoms between the above two groups in162patients (intermediate group). In onset group, the abdominal pain/discomfort was mild and the frequency was lower both in the "silent status"(no defecation) and before defecation. In the persistent group, more patients had abdominal pain (43.6%) in silent status with moderate (34.0%) and severe (7.4%) in severity,60.7%patients had abdominal pain/discomfort daily,20.2%had severe abdominal pain/discomfort before defecation. Patients with persistent symptoms had higher global bowel symptoms score than onset group (10.4±1.3vs8.7±1.1, P=0.000). There was no significant differences in HAMA and HAMD score among the three groups. The quality of life of IBS-D patients was decreased to76.2±16.2(n=67) in onset group, to71.7±18.3(n=112) in intermediate group, and to67.0±19.6(n=60) in persistent group (P=0.017).Thirty two subjects completed the colon manometry (each8cases in onset, remission, persistence and healthy control group). The quantity of high amplitude propulsive contractions (HAPCs) and low amplitude propulsive contractions (LAPCs) and motility index (MI) in the onset group were higher than the other three groups (P=0.019, P=0.000, P=0.001respectively) in the fasting phase, LAPCs and MI in postprandial phase were also higher than the other groups (P=0.018, P=0.000). The patients during onset also presented the significant higher response in intestinal resting pressure to a meal test (4.5±2.4mmHg). There was a positive correlation between motility index in fasting phase and the bowel symptoms score (r=0.761, P=0.028).Of30subjects’ fMRI data were included in the analysis (7cases in onset and remission group,8cases in persistence and healthy control group). We found the right parahippocampal gyrus, superior occipital gyrus and left superior frontal gyrus present with spontaneous brain activities for all IBS-D comparing with healthy subjects in the resting state. Patients with different episodic symptoms status presented with specific regions with spontaneous brain activities. Comparing with the remission patients, patients with episodic symptoms had increased activities in right frontal gyrus, and reduced activities in insula, precentral gyrus, postcentral gyrus, the right hippocampus and parahippocampal gyrus; while patients with persistent symptoms had increased activities right superior occipital gyrus, middle occipital gyrus, and inferior occipital gyrus comparing with episodic patients. There were some differences in the active brain regions associated with bowel symptoms score, quality of life score, and colonic motility index for patients in different symptoms status. The number of colonic mucosal EC cells with5-HT positive staining in onset group was significantly higher than the remission group (6.2vs4.0, P=0.001) and the persistent group (6.2vs5.0, P=0.020). There was no significant correlation between the number of EC and the bowel symptoms score. The total numbers of mast cells in the three groups were12.0(9.0)、13.5(9.3) and11.0(8.0) respectively, and the activated mast cells were2.0(1.0)、2.4(2.0) and2.0(1.0). There were no significant differences in the total number of mast cells, activated mast cells and the activation ratio among the three groups (P=0.127,P=0.108, P=0.898). In onset group there were significant positive correlation between the total number and activated mast cells and bowel symptoms score (ri=0.417, P1=0.004; r2=0.313, P2=0.034).Conclusions (1) IBS-D patients with different symptom episodic pattern had their semiological characteristics. Patients with onset or remission symptoms usually had mild abdominal pain/discomfort both in silent status and before defecation, with lower frequency, while the patients with persistent symptoms had more severe and frequent pain/discomfort with higher bowel symptoms score. There was no significant correlation between the psychological status and the IBS-D symptom onset. The intestinal symptoms impaired the patient’s quality of life, which was more obvious in patients with persistent symptoms.(2) The patients with episodic symptoms had active colonic motilities both in fasting and postprandial phases comparing with remission and persistent patients. Abnormalities of colonic motility play a major role in the pathophysiology of symptom onset.(3) The spontaneous brain activities in the resting state for IBS-D patients play an important role in symptom onset, remission or persistence.(4) The colonic mucosal enterochromaffin cells were related with the IBS-D symptom onset, while the mast cell and the activation of mast cell might be related to the IBS-D occurrence. The results from this study reveal the regularity and pathophysiological mechanisms for IBS-D symptom onset or persistence, which could be helpful for physician to improve the health cares for IBS-D patients. |
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