Is irritable bowel syndrome an organic disorder?

Irritable bowel syndrome(IBS)is a common gastrointestinal disorder that is generally considered to be functional because there appears to be no associated anatomical defect.Stress and psychological factors are thought to play an important role in IBS.The gut neuroendocrine system(NES),which regulates all functions of the gastrointestinal tract,consists of endocrine cells that are scattered among the epithelial cells of the mucosa,and the enteric nervous system.Although it is capable of operating independently from the centra nervous system(CNS),the gut NES is connected to and modulated by the CNS.This review presents evidence for the presence of an anatomical defect in IBS patients,namely in the gastrointestinal endocrine cells.These cells have specialized microvilli that project into the lumen and function as sensors for the luminal content and respond to luminal stimuli by releasing hormones into the lamina propria,which starts a chain reaction that progresses throughout the entire NES.The changes in the gastrointestinal endocrine cells observed in IBS patients are highly consistent with the other abnormalities reported in IBS patients,such as visceral hypersensitivity,dysmotility,and abnormal secretion.

High densities of serotonin and peptide YY cells in the colon of patients with lymphocytic colitis

AIM:To investigate colonic endocrine cells in lymphocytic colitis(LC) patients.METHODS:Fifty-seven patients with LC were included.These patients were 41 females and 16 males,with an average age of 49 years(range 19-84 years).Twenty-seven subjects that underwent colonoscopy with biopsies were used as controls.These subjects underwent colonoscopy because of gastrointestinal bleeding or health worries,where the source of bleeding was identified as haemorrhoids or angiodysplasia.They were 19 females and 8 males with an average age of 49 years(range 18-67 years).Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy.Biopsies were fixed in 4% buffered paraformaldehyde,embedded in paraffin and cut into 5 m-thick sections.The sections immunostained by the avidin-biotin-complex method for serotonin,peptide YY(PYY),pancreatic polypeptide(PP) enteroglucagon and somatostatin cells.The cell densities were quantified by computerised image analysis using Olympus software.RESULTS:The colon of both the patient and the control subjects were macroscopically normal.Histopathological examination of colon biopsies from controls revealed normal histology.All patients fulfilled the diagnosis criteria required for of LC:an increase in intraepithelial lymphocytes(> 20 lymphocytes/100 epithelial cells) and surface epithelial damage with increased lamina propria plasma cells and absent or minimal crypt architectural distribution.In the colon of both patients and control subjects,serotonin-,PYY-,PP-,enteroglucagon-and somatostatin-immunoreactive cells were primarily located in the upper part of the crypts of Lieberkühn.These cells were basket-or flask-shaped.There was no statistically significant difference between the right and left colon in controls with regards to the densities of serotonin-and PYYimmunoreactive cells(P = 0.9 and 0.1,respectively).Serotonin cell density in the right colon in controls was 28.9 ± 1.8 and in LC patients 41.6 ± 2.6(P = 0.008).In the left colon,the corresponding figures were 28.5 ± 1.9 and 42.4 ± 2.9,respectively(P = 0.009).PYY cell density in the right colon of the controls was 10.1 ± 1 and of LC patients 41 ± 4(P = 0.00006).In the left colon,PYY cell density in controls was 6.6 ± 1.2 and in LC patients 53.3 ± 4.6(P = 0.00007).CONCLUSION:The change in serotonin cells could be caused by an interaction between immune cells and serotonin cells,and that of PYY density might be secondary.

Endocrine cells in the oxyntic mucosa of the stomach in patients with irritable bowel syndrome

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). Fortythree age and sex-matched healthy volunteers withoutany 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 densityin 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 these2 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(Figures7 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.

Endocrine cells in the ileum of patients with irritable bowel syndrome

AIM:To study the ileal endocrine cell types in irritable bowel syndrome(IBS)patients.METHODS:Ninety-eight patients with IBS(77 females and 21 males;mean age 35 years,range 18-66 years)were included,of which 35 patients had diarrhea(IBS-D),31 patients had a mixture of both diarrhea and constipation(IBS-M),and 32 patients had constipation(IBS-C)as the predominant symptoms.The controls were 38 subjects(26 females and 12 males;mean age 40 years,range 18-65 years)who had submitted to colonoscopy for the following reasons:gastrointestinal bleeding,where the source of bleeding was identified as hemorrhoids(n=24)or angiodysplasia(n=3),and health worries resulting from a relative being diagnosed with colon carcinoma(n=11).The patients were asked to complete the:Birmingham IBS symptom questionnaire.Ileal biopsy specimens from all subjects were immunostained using the avidinbiotin-complex method for serotonin,peptide YY(PYY),pancreatic polypeptide(PP),enteroglucagon,and somatostatin cells.The cell densities were quantified by computerized image analysis,using Olympus cellSens imaging software.RESULTS:The gender and age distributions did not differ significantly between the patients and the controls(P=0.27 and P=0.18,respectively).The total score of Birmingham IBS symptom questionnaire was21±0.8,and the three underlying dimensions:pain,diarrhea,and constipation were 7.2±0.4,6.6±0.4,and 7.2±0.4,respectively.The density of serotonin cells in the ileum was 40.6±3.6 cells/mm2in the controls,and 11.5±1.2,10.7±5.6,10.0±1.9,and13.9±1.4 cells/mm2in the all IBS patients(IBS-total),IBS-D,IBS-M,and IBS-C patients,respectively.The density in the controls differed significantly from those in the IBS-total,IBS-D,IBS-M,and IBS-C groups(P<0.0001,P=0.0001,P=0.0001,and P<0.0001,respectively).There was a significant inverse correlation between the serotonin cell density and the pain dimension of Birmingham IBS symptom questionnaire(r=-0.6,P=0.0002).The density of PYY cells was 26.7±1.6 cells/mm2in the controls,and 33.1±1.4,27.5±1.4,34.1±2.5,and 41.7±3.1 cells/mm2in the IBStotal,IBS-D,IBS-M,and IBS-C patients,respectively.This density differed significantly between patients with IBS-total and IBS-C and the controls(P=0.03 and<0.0001,respectively),but not between controls and,IBS-D,and IBS-M patients(P=0.8,and P=0.1,respectively).The density of PYY cells correlated significantly with the degree of constipation as recorded by the Birmingham IBS symptom questionnaire(r=0.6,P=0.0002).There were few PP-,enteroglucagon-,and somatostatin-immunoreactive cells in the biopsy material examined,which made it impossible to reliably quantify these cells.CONCLUSION:The decrease of ileal serotonin cells is associated with the visceral hypersensitivity seen in all IBS subtypes.The increased density of PYY cells in IBS-C might contribute to the constipation experienced by these patients.