AIM: To study the different endocrine cell types in the oxyntic mucosa of patients with irritable bowel syndrome (IBS).METHODS: Seventy-six patients with IBS were included in the study (62 females and 14 males; mean age 32 years, range 18-55 years), of which 40 also fulfilled the Rome III criteria for functional dyspepsia (FDP). Of the entire IBS cohort, 26 had diarrhea as the predominant symptom (IBS-D), 21 had a mixture of diarrhea and constipation (IBS-M), and 29 had constipation as the predominant symptom (IBS-C). Forty-three age and sex-matched healthy volunteers without any gastrointestinal complaints served as controls. The patients were asked to complete the Birmingham IBS symptom questionnaire. Both the patients and controls underwent a standard gastroscopy, during which three biopsy samples were taken from the corpus. Sections from these biopsy samples were immunostained using the avidin-biotin complex (ABC) method, for ghrelin, serotonin, somatostatin and histamine. The densities of these cell types and immunoreactivity intensities were quantified using computerized image analysis with Olympus cellSens imaging software (version 1.7).RESULTS: The densities of the ghrelin cells in the control, IBS-total, IBS-D, IBS-M and IBS-C groups were 389 (320, 771), 359 (130, 966), 966 (529, 1154), 358 (120, 966) and 126 (0, 262) cells/mm2, respectively. There was a significant difference between the tested groups (P < 0.0001). Dunn’s multiple comparison test showed that the ghrelin cell density was significantly higher in IBS-D and lower in IBS-C than in the controls (P = 0.03 and 0.0008, respectively). The ghrelin cell density in patients with both IBS and FDP was 489 (130, 966), and in those with IBS only 490 (130, 956). There was no statistical significant difference between these 2 groups of patients (P = 0.9). The immunoreactivity intensity did not differ between any of the groups (P = 0.6). The diarrhea score of the Birmingham IBS symptom questionnaire was significantly positively correlated with ghrelin cell density (r = 0.65; P < 0.0001) and significantly inversely correlated with that of constipation (r = 90.69; P < 0.0001). The densities of the serotonin cells were 63 (51, 82), 51 (25, 115), 120 (69, 128), 74 (46, 123) and 40 (0, 46) cells/mm2 in the control, IBS-total, IBS-D, IBS-M and IBS-C groups, respectively. A statistically significant difference was found between the tested groups (P < 0.0001). Posttest revealed that serotonin cell density was significantly higher in IBS-D and lower in IBS-C than in controls (P = 0.02 and 0.004, respectively), but did not differ in the IBS-total and IBS-M groups from that in controls (P = 0.5 and 0.4, respectively). The serotonin cell density in patients with both IBS and FDP was 62 (25, 115) and in those with IBS only 65 (25, 123). There was no statistically significant difference between these 2 groups of patients (P = 1). The immunoreactivity intensity of serotonin did not differ significantly between any of the groups (P = 0.0.9). The serotonin cell density was significantly positively correlated with the diarrhea score of the Birmingham IBS symptom questionnaire (r = 0.56; P < 0.0001) and significantly inversely correlated with that of constipation (r = 0.51; P < 0.0001). The densities of the somatostatin cells were 97 (72, 126), 72 (0, 206), 29 (0, 80), 46 (0, 103) and 206 (194, 314) cells/mm2 in the control, IBS-total, IBS-D, IBS-M and IBS-C groups, respectively (Figures 7 and 8). There was a statistically significant difference between the controls and the IBS subgroups (P < 0.0001). The density of somatostatin cells was significantly lower in the IBS-D and IBS-M groups but higher in IBS-C patients than in the controls (P < 0.01, P = 0.02, and P = 0.0008, respectively). The somatostatin cell density in patients with both IBS and FDP was 86 (0-194), and in those with IBS only 110 (0-206). There was no statistically significant difference between these 2 groups of patients (P = 0.6). There was no significant difference in somatostatin immunoreactivity intensity between the controls. The diarrhea score of the Birmingham IBS symptom questionnaire was inversely correlated with somatostatin cell density (r = 0.38; P = 0.0007) and was positively correlated with that of constipation (r = 0.64; P < 0.0001).CONCLUSION: The finding of abnormal endocrine cells in the oxyntic mucosa shows that the endocrine cell disturbances in IBS are not restricted to the intestine. Furthermore, it appears that ghrelin, serotonin and somatostatin in the oxyntic mucosa of the stomach may play an important role in the changing stool habits in IBS through their effects on intestinal motility.
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机译：目的：研究肠易激综合征（IBS）患者的氧化性黏膜中不同的内分泌细胞类型。方法：纳入研究的76例IBS患者（女性62例，男性14例；平均年龄32岁，范围18 -55岁），其中40个还符合罗马三世的功能性消化不良（FDP）标准。在整个IBS队列中，以腹泻为主要症状（IBS-D），有21腹泻和便秘混合存在（IBS-M），以便秘为主要症状（IBS-C）占21。 43名没有胃肠道不适的年龄和性别匹配的健康志愿者作为对照。要求患者填写伯明翰IBS症状问卷。患者和对照组均接受了标准胃镜检查，在此期间从主体中采集了三个活检样本。使用抗生物素蛋白-生物素复合物（ABC）方法对这些活检样品的切片进行免疫染色，以检测生长素释放肽，血清素，生长抑素和组胺。使用Olympus cellSens成像软件（版本1.7）通过计算机图像分析对这些细胞类型的密度和免疫反应强度进行定量。结果：对照组，IBS-total，IBS-D，IBS-M和IBS的ghrelin细胞的密度-C组分别为389（320，771），359（130，966），966（529，1154），358（120，966）和126（0，262）个细胞/ mm 2 分别。测试组之间存在显着差异（P <0.0001）。邓恩（Dunn）的多重比较测试显示，与对照组相比，IBS-D中的生长素释放肽细胞密度明显高于对照组，而IBS-C中的ghrelin细胞密度则明显低于对照组（分别为P = 0.03和0.0008）。 IBS和FDP患者的ghrelin细胞密度均为489（130，966），而IBS只有490（130，956）。两组患者之间无统计学差异（P = 0.9）。两组之间的免疫反应强度无差异（P = 0.6）。伯明翰IBS症状问卷的腹泻评分与生长素释放肽细胞密度呈显着正相关（r = 0.65； P <0.0001），与便秘则呈显着负相关（r = 90.69; P <0.0001）。血清素细胞的密度分别为63（51，82），51（25，115），120（69，128），74（46，123）和40（0，46）细胞/ mm 2 P <0.0001 ）。生长抑素细胞的密度分别为97（72，126），72（0，206），29（0，80），46（0，103）和206（194，314）/ mm 2 P <0.0001）。 IBS-D和IBS-M组的生长抑素细胞密度明显低于对照组，而IBS-C组则高于对照组（ P <0.01， P = 0.02和 P = 0.0008）。 IBS和FDP患者的生长抑素细胞密度均为86（0-194），IBS患者仅为110（0-206）。这两组患者之间没有统计学差异（ P = 0.6）。对照之间的生长抑素免疫反应强度没有显着差异。伯明翰IBS症状问卷的腹泻评分与生长抑素细胞密度呈负相关（ r = 0.38； P = 0.0007），与便秘的得分呈正相关（ > r = 0.64; P <0.0001）。结论：在氧化性粘膜中发现异常内分泌细胞表明，IBS中的内分泌细胞紊乱不仅限于肠道。此外，似乎胃的氧化性粘膜中的生长素释放肽，5-羟色胺和生长抑素可能通过影响肠蠕动而在改变IBS的大便习惯中发挥重要作用。
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