Tarek Mazzawi

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.

Effects of dietary guidance on the symptoms, quality of life and habitual dietary intake of patients with irritable bowel syndrome

Diet is important in triggering the symptoms of irritable bowel syndrome (IBS). This study investigated the impact of dietary guidance on the symptoms, quality of life and habitual diet of patients with IBS. Forty-six patients who fulfilled the Rome III criteria for the diagnosis of IBS were included. Of these patients, 17 completed the entire study. Each patient attended three sessions (~45 min in duration) and received individual guidance on their dietary management. The patients were asked to complete the following questionnaires prior to receiving the dietary guidance, and at least 3 months subsequently: The Birmingham IBS symptom score questionnaire, the IBS Quality of Life (IBS-QOL) questionnaire, the Short-Form Nepean and Dyspepsia Index (SF‑NDI) and the MoBa Food Frequency Questionnaire (MoBa FFQ). The time at which patients completed the questionnaires following dietary guidance ranged from 3-9 months (median, 4 months). The total IBS symptom scores were reduced once the patients had received dietary guidance (P=0.001). The total score for the quality of life, as assessed by the IBS‑QOL and the SF-NDI, increased significantly following the dietary guidance sessions (P=0.003 and P=0.002, respectively). There were no statistical differences in the intake of calories, carbohydrate, fiber, protein, fat or alcohol in the patients with IBS following dietary guidance. There were increases in the consumption of dairy products, β-carotene, retinol equivalents, riboflavin, vitamin B12 and calcium, although only the increase in vitamin B12 consumption was statistically significant. There was a significant reduction in the consumption of certain fruits and vegetables that were rich in highly fermentable short-chain carbohydrates, disaccharides, monosaccharides and polyols, as well as insoluble fibers. In conclusion, three 45-min dietary guidance sessions, administered by a nurse, reduced the symptoms and improved the quality of life of patients with IBS, and resulted in an adequate intake of vitamins and minerals. Individual dietary guidance is a cost-effective option for the management of IBS.

Chromogranin A cell density in the rectum of patients with irritable bowel syndrome.

In a previous study, chromogranin A (CgA) cell density in the colon of patients with irritable bowel syndrome (IBS) was found to be reduced. It has been suggested that intestinal CgA cell density may be used as a marker for the diagnosis of IBS. The rectum harbours a larger number of large intestinal endocrine cells and is more accessible for biopsies than the colon. The present study aimed at determining the CgA cell density in the rectum of IBS patients. A total of 47 patients with IBS that fulfilled the Rome Criteria III (39 females and 8 males; average age, 38 years) were included. A total of 28 patients had diarrhea (IBS-D) and 19 had constipation (IBS-C) as the predominant symptom. A total of 27 subjects that underwent colonoscopy with rectal biopsies were used as the controls. These subjects underwent colonoscopy due to gastrointestinal bleeding (the source of which was identified as haemorrhoids or angiodysplasia; 19 females and 8 males; average age, 49 years), or health worries. The rectal biopsies were immunostained for CgA and quantified by computer image analysis. The CgA density in the controls was 206.3±22.2 (mean ± SEM), in all IBS patients 190.2±14.3, in IBS-D patients 188.8±14.7 and in IBS-C patients 195.3±34.1. There was no statistically significant difference between the controls, IBS, IBS-D or IBS-C patients (P=0.5, 0.5 and 0.7, respectively). The present study showed that although the rectum comprises the same endocrine cell types as the colon, attention must be paid when drawing conclusions regarding the whole large intestine from studies carried out on the rectum. This particularly applies when endocrine cells are investigated. As CgA cell density represents the total endocrine cell content of the rectum, changes in specific endocrine cells in IBS patients cannot be excluded.

Increased gastric chromogranin A cell density following changes to diets of patients with irritable bowel syndrome

The gut endocrine cells control and regulate several functions of the gastrointestinal tract. They have been reported to be abnormal in irritable bowel syndrome (IBS), with alterations occurring in several functions regulated by these cells. Furthermore, it has been established that gut endocrine cells interact with the gut lumen contents, particularly the nutrients. The present study was undertaken to establish whether the positive outcome of dietary guidance observed in patients suffering from IBS is associated with a change in gastric endocrine cells. A total of 46 patients with IBS participated in the present study, of which 14 completed all aspects. These patients included nine females and five males with a mean age of 34 years (range, 20–45 years). In the healthy control group, nine females and five males, with a mean age of 54 years (range 26–70 years) were selected. The patients and controls underwent gastroscopy with biopsy samples taken from the corpus and antrum of the stomach. Each patient attended three sessions that lasted ~45 min each, and received individual guidance on their dietary management. The patients followed the diet prescribed for a minimum of three months, then further samples were taken using a method similar to that used for the initial biopsies. The biopsy samples were immunostained using the avidin-biotin complex method for chromogranin A (CgA) and quantified by computerized image analysis. The patients with IBS presented a low density of CgA compared with the controls. The density of CgA increased in these patients following dietary guidance and changes in food intake. The present observations emphasized the interaction between food intake and gut endocrine cells. The current study also suggests that the positive effects of dietary guidance may be attributed to changes in gut endocrine cell density.

Effect of dietary management on the gastric endocrine cells in patients with irritable bowel syndrome.

Background/objectives:The gastric endocrine cells in patients with irritable bowel syndrome (IBS) tend to normalize following dietary guidance. The aim of the present study was to identify the gastric endocrine cell types that are changed following such dietary guidance.Subjects/methods:Fourteen IBS patients and 14 healthy subjects were included in the study. Patients received three sessions of individual dietary management guidance. Gastroscopy was performed on both the controls and the patients at baseline and then again for the patients at 3–9 months after dietary guidance. Biopsy samples from the corpus and antrum were immunostained for all gastric endocrine cell types. Endocrine cells were quantified by computerized image analysis.Results:The densities of the ghrelin cells for the controls and IBS patients before and after dietary guidance were 149.6±36.2 (mean±s.e.m.; 95% confidence interval (CI) 71.3–227.8), 114.5±32.7 and 161.8±37.8 cells/mm2, respectively. The densities of the gastrin cells in these groups were 155.8±21.0 (95% CI 110.3–201.2), 159.4±24.3 and 211.6±28.0 cells/mm2, respectively; the corresponding densities of serotonin cells in the corpus were 18.2±3.9 (95% CI 9.8–26.6), 10.6±3.4 and 14±2.0 cells/mm2 and in the antrum were 44.6±12.2 (95% CI 18.1–71.1), 1.7±0.5 and 14.7±6.3 cells/mm2. The densities of the somatostatin cells in the corpus were 40.0±7.7 (95% CI 23.5–56.5), 23.0±3.0 and 37.3±4.2 cells/mm2, respectively, and in the antrum were 138.9±22.0 (95% CI 91.4–186.3), 95.6±15.9 and 86.0±16.9 cells/mm2, respectively.Conclusions:The densities of all of the gastric endocrine cell types changed towards the healthy control values in the IBS patients following a change in food intake.

Dietary guidance normalizes large intestinal endocrine cell densities in patients with irritable bowel syndrome

Background/Objectives:To determine the large intestinal endocrine cell types affected following dietary guidance in patients with irritable bowel syndrome (IBS).Subjects/Methods:The study included 13 IBS patients and 13 control subjects. The patients received three sessions of individualized dietary guidance. Both the control subjects and the patients were scheduled for colonoscopies at baseline and again for the patients at 3–9 months after dietary guidance. Biopsy samples were taken from the colon and rectum and were immunostained for all types of large intestinal endocrine cells. The endocrine cells were quantified using computerized image analysis.Results:The daily total consumption (mean±s.e.m. values) of fruits and vegetables rich in FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) decreased significantly from 16.2±5.3 g before receiving dietary guidance to 9.2±3.2 g after receiving dietary guidance (P=0.02). In the total colon, the densities of serotonin cells were 46.8±8.9, 10.5±2.1 and 22.6±3.2 cells/mm2 in control subjects and in IBS patients before and after receiving dietary guidance, respectively (P=0.007); the corresponding densities of peptide YY cells were 11.6±1.8, 10.8±1.7 and 16.8±2.1 cells/mm2, respectively (P=0.06). The cell densities for both serotonin and peptide YY did not change significantly in the rectum. The densities of somatostatin cells in the rectum were 13.5±3.0, 13.2±3.0, and 22.3±3.2 cells/mm2 for control subjects and for IBS patients before and after receiving dietary guidance, respectively (P=0.01).Conclusions:The densities of the large intestinal endocrine cells tend to normalize following dietary guidance that may have contributed to the improvement of the patients with IBS symptoms.

Changes in small intestinal chromogranin A-immunoreactive cell densities in patients with irritable bowel syndrome after receiving dietary guidance

Chromogranin A (CgA) is a common marker for enteroendocrine cells in the gut, and CgA-immunoreactive cell densities are abnormal in patients with irritable bowel syndrome (IBS). The majority of patients with IBS report that their symptoms develop after consuming certain foodstuffs. In the present study, we investigated the effects of dietary guidance on the total enteroendocrine cell densities in the small intestine, as detected by CgA. A total of 14 patients with IBS underwent a gastroscopy with duodenal biopsies and 11 of them also underwent a colonoscopy, with biopsy samples obtained from the ileum. Fourteen control subjects were also included. Each patient received 3 sessions of dietary guidance. Gastroscopies and colonoscopies were performed on both the controls and patients with IBS (at baseline and at 3–9 months after receiving guidance). Biopsy samples obtained from the duodenum and ileum were immunostained for CgA using the avidin-biotin complex (ABC) method and were quantified using computerized image analysis. The density of CgA-immunoreactive cells in the duodenum (mean ± SEM values) in the control subjects was 235.9±31.9 cells/mm2; in the patients with IBS, the density was 36.9±9.8 and 103.7±16.9 cells/mm2 before and after they received dietary guidance, respectively (P=0.007). The density of CgA-immunoreactive cells in the ileum in the control subjects was 47.4±8.3 cells/mm2; in the patients with IBS, the density was 48.4±8.1 and 17.9±4.4 cells/mm2, before and after they received dietary guidance, respectively (P=0.0006). These data indicate that changes in CgA-immunoreactive cell densities in patients with IBS after receiving dietary guidance may reflect a change in the densities of the small intestinal enteroendocrine cells, which may contribute to an improvement in the IBS symptoms.

Increased chromogranin A cell density in the large intestine of patients with irritable bowel syndrome after receiving dietary guidance

The large intestine contains five types of endocrine cells that regulate its functions by sensing its luminal contents and releasing specific hormones. Chromogranin A (CgA) is a common marker for the gastrointestinal endocrine cells, and it is abnormal in irritable bowel syndrome (IBS) patients. Most IBS patients relate their symptoms to certain food elements. The present study investigated the effect of dietary guidance on the total endocrine cells of the large intestine as detected by CgA in 13 IBS patients. Thirteen control subjects were also included. Each patient received three sessions of dietary guidance. Colonoscopies were performed on controls and patients (at baseline and at 3–9 months after receiving guidance). Biopsy samples from the colon and rectum were immunostained for CgA and quantified by computerized image analysis. The densities of CgA cells in the total colon (mean ± SEM) among the controls and the IBS patients before and after receiving dietary guidance were 83.3 ± 10.1, 38.6 ± 3.7, and 64.7 ± 4.2 cells/mm2, respectively (P = 0.0004), and were unchanged in the rectum. In conclusion, the increase in CgA cell density after receiving dietary guidance may reflect a change in the densities of the large intestinal endocrine cells causing an improvement in the IBS symptoms.

Interaction between diet and gastrointestinal endocrine cells (Review)

The gastrointestinal endocrine cells are essential for life. They regulate the gastrointestinal motility, secretion, visceral sensitivity, absorption, local immune defense, cell proliferation and appetite. These cells act as sensory cells with specialized microvilli that project into the lumen that sense the gut contents (mostly nutrients and/or bacteria byproducts), and respond to luminal stimuli by releasing hormones into the lamina propria. These released hormones exert their actions by entering the circulating blood and reaching distant targets (endocrine mode), nearby structures (paracrine mode) or via afferent and efferent synaptic transmission. The mature intestinal endocrine cells are capable of expressing several hormones. A change in diet not only affects the release of gastrointestinal hormones, but also alters the densities of the gut endocrine cells. The interaction between ingested foodstuffs and the gastrointestinal endocrine cells can be utilized for the clinical management of gastrointestinal and metabolic diseases, such as irritable bowel syndrome, obesity and diabetes.

Enteroendocrine cells, stem cells and differentiation progenitors in rats with TNBS-induced colitis

Patients with inflammatory bowel disease (IBD), as well as animal models of human IBD have abnormal enteroendocrine cells. The present study aimed to identify the possible mechanisms underlying these abnormalities. For this purpose, 40 male Wistar rats were divided into 4 groups as follows: the control group, the group with trinitrobenzene sulfonic acid (TNBS)-induced colitis with no treatment (TNBS group), the group with TNBS-induced colitis treated with 3-[(dodecylthiocarbonyl)-methyl]-glutarimide (DTCM-G; an activator protein-1 inhibitor) (DTCM-G group), and the group with TNBS-induced colitis treated with dehydroxymethylepoxyquinomicin (DHMEQ; a nuclear factor-κB inhibitor) treatment (DHMEQ group). Three days following the administration of TNBS, the rats were treated as follows: those in the control and TNBS groups received 0.5 ml of the vehicle [0.5% carboxymethyl cellulose (CMC)], those in the DTCM-G group received DTCM-G at 20 mg/kg body weight in 0.5% CMC, and those in the DHMEQ group received DHMEQ at 15 mg/kg body weight in 0.5% CMC. All injections were administered intraperitoneally twice daily for 5 days. The rats were then sacrificed, and tissue samples were taken from the colon. The tissue sections were stained with hemotoxylin-eosin and immunostained for chromogranin A (CgA), serotonin, peptide YY (PYY), oxyntomodulin, pancreatic polypeptide (PP), somatostatin, Musashi1 (Msi1), Math1, Neurogenin3 (Neurog3) and NeuroD1. The staining was quantified using image analysis software. The densities of CgA-, PYY-, PP-, Msi1-, Neurog3- and NeuroD1-positive cells were significantly lower in the TNBS group than those in the control group, while those of serotonin-, oxyntomodulin- and somatostatin-positive cells were significantly higher in the TNBS group than those in the control group. Treatment with either DTCM-G or DHMEQ restored the densities of enteroendocrine cells, stem cells and their progenitors to normal levels. It was thus concluded that the abnormalities in enteroendocrine cells and stem cells and their differentiation progenitors may be caused by certain signaling substances produced under inflammatory processes, resulting in changes in hormone expression in enteroendocrine cells. These substances may also interfere with the colonogenic activity and the differentiation of the stem-cell secretory lineage into mature enteroendocrine cells.