Magdy El-Salhy

Irritable bowel syndrome: Diagnosis and pathogenesis

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder that considerably reduces the quality of life. It further represents an economic burden on society due to the high consumption of healthcare resources and the non-productivity of IBS patients. The diagnosis of IBS is based on symptom assessment and the Rome III criteria. A combination of the Rome III criteria, a physical examination, blood tests, gastroscopy and colonoscopy with biopsies is believed to be necessary for diagnosis. Duodenal chromogranin A cell density is a promising biomarker for the diagnosis of IBS. The pathogenesis of IBS seems to be multifactorial, with the following factors playing a central role in the pathogenesis of IBS: heritability and genetics, dietary/intestinal microbiota, low-grade inflammation, and disturbances in the neuroendocrine system (NES) of the gut. One hypothesis proposes that the cause of IBS is an altered NES, which would cause abnormal GI motility, secretions and sensation. All of these abnormalities are characteristic of IBS. Alterations in the NES could be the result of one or more of the following: genetic factors, dietary intake, intestinal flora, or low-grade inflammation. Post-infectious IBS (PI-IBS) and inflammatory bowel disease-associated IBS (IBD-IBS) represent a considerable subset of IBS cases. Patients with PI- and IBD-IBS exhibit low-grade mucosal inflammation, as well as abnormalities in the NES of the gut.

Diet and effects of diet management on quality of life and symptoms in patients with irritable bowel syndrome

The present study investigated the diet and quality of life of irritable bowel syndrome (IBS) patients in comparison to the background population. Furthermore, it studied the effects of guidance on diet management on changes in food intake, quality of life and symptoms. A total of 35 healthy controls, 36 IBS patients and 43 IBS patients who had received guidance on diet management 2 years earlier were included. The controls and patients were asked to complete an FFQ questionnaire, an SF-NDI questionnaire, an IBS-QoL questionnaire and a Birmingham IBS symptom score questionnaire. There were no statistical differences in the intake of calories, carbohydrates, proteins and fat between the controls and IBS patients, with or without guidance on diet management. IBS patients made a conscious choice to avoid certain food items, some of which belong to fermentable oligosaccharides, disaccharides, monosacharides and polyols (FODMAPs). They had a higher consumption, however, of other food items that are rich in FODMAPs. They also avoided other food sources which are crucial for their health. Two years after receiving guidance on diet management, IBS patients had a different diet profile. They avoided all FODMAP‑rich food, consumed more food with probiotic supplements and did not avoid food sources that were crucial to their health. In addition, they had improved quality of life and reduced symptoms. Although at first sight the diet of IBS patients did not differ from that of the background population, detailed examination showed avoidance of certain food items. Guidance on the management of diet improved their choice of a healthier diet, improved quality of life and reduced IBS symptoms.

Relative importance of abnormalities of CCK and 5-HT (serotonin) in Giardia-induced post-infectious irritable bowel syndrome and functional dyspepsia

Aliment Pharmacol Ther 31, 883–891

Chromogranin A as a possible tool in the diagnosis of irritable bowel syndrome

Abstract Objective. Serum chromogranin A (CgA) levels have been reported to be normal, reduced or elevated in irritable bowel syndrome (IBS) patients. The aim of the present study was to establish a possible abnormality in CgA plasma level and in intestinal CgA cell density in IBS patients and to evaluate the outcome for the diagnosis of IBS. Material and methods. Forty-one patients with irritable bowel syndrome according to Rome Criteria III (39 females and 2 males; average age 35 years) and 59 healthy controls (37 females and 22 males; average age 45.5 years) were included in the study. Duodenal and colonic biopsies were obtained from all IBS patients. Forty-two of these healthy subjects underwent gastroscopy with duodenal biopsies. The remaining 17 subjects underwent colonoscopy with biopsies. The biopsies were immunostained with avidin–biotin-complex method for CgA cells. The cell densities were quantified by computerized image analysis. CgA plasma level was determined with ELISA technique. Results. The density of CgA cells in both the duodenum and colon was reduced in patients with IBS. CgA cell density in the left colon was, however, unaffected in patients with IBS-constipation. There was no difference in the plasma level of CgA between patients with IBS and controls. Conclusion. The reduced density of intestinal CgA cells should be considered as a reduction in the total amount of intestinal endocrine cells. Which endocrine cell type is affected remains to investigate. This reduction may offer a histopathological test for the diagnosis of IBS. It is doubtful that the blood level of CgA has any clinical impact in IBS.

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 μm-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 PYY-immunoreactive 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.

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 central 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.

Abnormal Small-Intestinal Endocrine Cells in Patients with Irritable Bowel Syndrome

BackgroundGeneral disturbances in gastrointestinal motility have been reported in patients with irritable bowel syndrome (IBS). The gastrointestinal tract hormones play an important role in regulating gastrointestinal motility.AimsTo investigate a possible abnormality in the small intestinal endocrine cells of IBS patients.MethodsIncluded in the study were 41 patients with irritable bowel syndrome according to Rome Criteria III and 42 healthy controls. Duodenal biopsies were obtained from both patients and controls during gastroscopy. The biopsies were immunostained by avidin–biotin-complex method for secretin, CCK, GIP, somatostatin, and serotonin cells. The cell densities were quantified by computerized image analysis.ResultsThe density of secretin- and CCK-immunoreactive cells in patients with IBS was significantly reduced. The reduction in secretin and CCK cells occurred only in IBS-diarrhea patients, but not in IBS-constipation subtype. Both GIP and somatostatin cell densities were reduced in the duodenum of IBS patients. There was no statistical difference between the subtypes of IBS patients, regarding secretin, CCK, GIP, or somatostatin cell densities. Serotonin cell density was not affected in patients with IBS.ConclusionsThe low densities of secretin and CCK cells in IBS-diarrhea patients may cause a functional pancreatic insufficiency as well as inadequate gall emptying, as these hormones stimulate pancreatic bicarbonate and enzyme secretion and CCK stimulates as well gall bladder contraction. Low densities of secretin, GIP, and somatostatin cells in IBS patients might result in a high secretion of gastric acid, as secretin, GIP, and somatostatin inhibit gastric acid secretion.

Low densities of serotonin and peptide YY cells in the colon of patients with irritable bowel syndrome.

BackgroundThe gut hormones are important in regulating gastrointestinal motility. Disturbances in gastrointestinal motility have been reported in patients with irritable bowel syndrome (IBS). Reduced endocrine cell density, as revealed by chromogranin A, has been reported in the colon of IBS patients.AimsTo investigate a possible abnormality in the colonic endocrine cells of IBS patients.MethodsA total of 41 patients with IBS according to Rome Criteria III and 20 controls were included in the study. Biopsies from the right and left colon were obtained from both patients and controls during colonoscopy. The biopsies were immunostained for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), entroglucagon, and somatostatin cells. Cell densities were quantified by computerized image analysis.ResultsSerotonin and PYY cell densities were reduced in the colon of IBS patients. PP, entroglucagon, and somatostatin-immunoreactive cells were too few to enable reliable quantification.ConclusionThe cause of these observations could be primary genetic defect(s), secondary to altered serotonin and/or PYY signaling systems and/or subclinical inflammation. Serotonin activates the submucosal sensory branch of the enteric nervous system and controls gastrointestinal motility and chloride secretion via interneurons and motor neurons. PYY stimulates absorption of water and electrolytes, and inhibits prostaglandin (PG) E2, and vasoactive intestinal peptide, which stimulates intestinal fluid secretion and is a major regulator of the “ileal brake”. Although the cause and effect relationship of these findings is difficult to elucidate, the abnormalities reported here might contribute to the symptoms associated with IBS.

The role of peptide YY in gastrointestinal diseases and disorders (Review)

Peptide YY (PYY) is affected in several gastrointestinal diseases and disorders. Changes in PYY appear to be an adaptive response to alterations in pathophysiological conditions caused by the disease. This applies to gastrointestinal diseases/disorders such as irritable bowel syndrome, inflammatory bowel disease, celiac disease, systemic sclerosis, and post-intestinal resection. By contrast, the changes in PYY in chronic idiopathic slow transit constipation (CST) seem to be of a primary nature, and may be one etiological factor of the disease. Abnormalities in PYY seem to contribute to the development of symptoms present in irritable bowel syndrome, inflammatory bowel disease, gastroenteropathy in long-standing diabetes and CST. The changes in PYY could, however, be favorable in some gastrointestinal disorders such as celiac disease, systemic sclerosis and post-intestinal resection state. Investigating changes in PYY in gastrointestinal diseases/disorders could be beneficial in clinical practice, where a receptor agonist or an antagonist can be used as a drug, depending on the condition. Similar to other neuroendocrine peptides/amines of the gut, PYY has broad physiological/pharmacological effects: it can bind to and activate several receptors with independent actions. Thus, in order to use PYY as a drug, receptor-specific agonists or antagonists need to be developed.

Abnormal rectal endocrine cells in patients with irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. In a previous study the total number of endocrine cells in the rectum of IBS patients, as detected by chromogranin A, did not differ from that of healthy controls. While the total endocrine cell content of the rectum appears to be unchanged in IBS patients, changes in particular endocrine cells cannot be excluded. This study was undertaken, therefore, to investigate the cell density of different rectal endocrine cell types in (IBS) patients. Fifty patients with IBS (41 females and 9 males) were included in the study. Thirty patients had diarrhoea (IBS-D) and 20 had constipation (IBS-C) as the predominant symptom. Twenty-seven subjects were included as controls (19 females and 8 males). Rectal biopsy specimens were immunostained using the avidin-biotin-complex method for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), and oxyntomodulin and somatostatin cells. The cell densities were quantified by computerised image analysis. The serotonin cell density did not differ significantly, although a type II statistical error cannot be excluded, due to the small size of the sample. The densities of PYY and Oxyntomodulin cells were significantly lower and that of somatostatin were significantly higher in IBS patients than controls. These abnormalities were observed in both IBS-D and IBS-C patients. The abnormalities in the endocrine cells observed in this study in the rectum differed considerably from those seen in the colon of IBS patients. This indicates that caution in using the rectum to represent the large intestine in these patients. These abnormalities could be primary (genetic) or secondary to changes in the gut hormones found in other segments of the gut and/or other pathological processes. Although the-cause-and effect relationship of the abnormalities found in rectal endocrine cells is difficult to elucidate, they might contribute to the symptoms associated with IBS. The densities of PYY and somatostatin cells are potential biomarkers with good sensitivity and specificity for the diagnosis of IBS.