Irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders. It is a multifactorial disorder with its pathogenesis attributed to abnormal gastrointestinal motility, low-grade inflammation, visceral hypersensitivity, communication in the gut-brain axis, and so on. Traditionally, IBS has been treated with diet and lifestyle modification, fiber supplementation, psychological therapy, and pharmacological treatment. Carbohydrates are intermingled with a wide range of regularly consumed food including grains such as rye and wheat, vegetables, fruits, and legumes. Short-chain carbohydrates that are poorly absorbed exert osmotic effects in the intestinal lumen increasing its water volume, and are rapidly fermented by bacteria with consequent gas production. These effects may be the basis for the induction of most of the gastrointestinal symptoms. This has led to the use of lactose-free diets in those with lactose intolerance and of fructose-reduced diets for fructose malabsorption. As all poorly absorbed short-chain carbohydrates have similar and additive effects in the intestine, a concept has been developed to regard them collectively as FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) and to evaluate a dietary approach that restricts them all. Based on the observational and comparative studies, and randomized-controlled trials, FODMAPs have been shown to trigger gastrointestinal symptoms in patients with IBS. Food choice via the low FODMAPs and potentially other dietary strategies is now a realistic and efficacious therapeutic approach for managing symptoms of IBS.
*Diet, Carbohydrate-Restricted ; Dietary Supplements ; Humans ; Hypersensitivity/complications ; Inflammation/complications ; Intestines/pathology ; Irritable Bowel Syndrome/complications/*diagnosis/diet therapy ; Malabsorption Syndromes/complications ; Monosaccharides/metabolism ; Oligosaccharides/metabolism

OBJECTIVETo observe the effect of Tongxie Yaofang (TY) on the number of mast cells (MCs) and the expression of cytokines in rats with visceral hypersensitivity, and to explore roles of TY in treating visceral hypersensitivity and its possible mechanism.

METHODSTotally 30 male adult Sprague Dawley (SD) rats were randomly divided into the blank control group, the model group, and the TY treatment group, 10 in each group. The irritable bowel syndrome (IBS) rat model was established by combining colorectal distention with restraint stress in the TY treatment group and the model group. The visceral hypersensitivity was assessed by abdominal withdrawal reflex (AWR). From the 2nd day of successful modeling, rats in the treatment group were admiministered with TY at the daily dose of 4 g/kg for 4 successive weeks. Equal volume of normal saline was given to rats in the model group for 4 successive weeks. No treatment was given to rats in the blank control group. Four weeks later the number of MCs was counted by using toluidine blue staining. The expression of interleukin-4 (IL-4) and interleukin-9 (IL-9) both in colonic mucosa and serum were measured by enzyme linked immunosorbent assay (ELISA), and the expression of protease-activated receptor type 2 (PAR-2) was detected by Western blot.

RESULTSCompared with the blank control group, the visceral sensitivity was significantly elevated, the number of MCs in the ileocecal junction increased, and the expression of IL-4, IL-9, and PAR-2 in serum and the colonic mucosa significantly increased (P < 0.05). Compared with the model group, the visceral sensitivity significantly decreased, the number of MCs reduced, and the expression of PAR-2 in the colonic mucosa significantly reduced (all P < 0.05), and the expression of IL-4 in colonic mucosa and IL-9 in serum were obviously reduced in the TY treatment group (P < 0.05).

CONCLUSIONTY might improve the visceral hypersensitivity by acting on MCs related cytokines and reducing degranulation of MCs.

Animals ; Cytokines ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Intestines ; drug effects ; metabolism ; pathology ; Irritable Bowel Syndrome ; drug therapy ; metabolism ; pathology ; Male ; Mast Cells ; drug effects ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the effect of Shugan Jianpi Granule (, SJG) on the number of gut mucosal serotonin-positive cells (5-HT+C) in patients with irritable bowel syndrome (IBS) of stagnated Gan-qi attacking Pi (SGAP) syndrome type.

METHODSTwenty-four patients were randomized equally into three groups. All were treated with the basic conventional treatment by cognition-behavior therapy with assistance of lactein 3 tablets thrice a day. Additionally, 24 g of SJG was given three times a day to group A, and the same dosage of SJG and Smecta 15 g thrice a day was given to group B, while no additional treatment was given to the control group. The number of 5-HT+C was measured respectively before and two weeks after treatment by immunohistochemical method.

RESULTSThe number of 5-HT+C decreased after treatment in all the three groups (P<0.05), but the decrement was more significant in the two test groups than in the control group (P<0.05 and P<0.01, respectively), while comparison of 5-HT+C between the two test groups showed insignificant difference (P>0.05).

CONCLUSIONSJG can reduce the number of 5-HT+C in IBS patients of SGAP syndrome type, and its effect is enhanced when used in combination with Smecta.

Adult ; Cell Count ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Humans ; Immunohistochemistry ; Intestinal Mucosa ; drug effects ; pathology ; Irritable Bowel Syndrome ; drug therapy ; pathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Phytotherapy ; Serotonin ; metabolism ; Syndrome

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional intestinal diseases, but its pathogenesis is still unknown. The present study aimed to screen the differentially expressed proteins in the mucosa of colon between IBS with diarrhea (IBS-D) patients and the healthy controls. METHODS: Forty-two IBS-D patients meeting the Rome III diagnostic criteria and 40 control subjects from July 2007 to June 2009 in Chinese PLA General Hospital were enrolled in the present study. We examined the protein expression profiles in mucosa of colon corresponding to IBS-D patients (n = 5) and controls (n = 5) using 2-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). Secondly, Western blot and immunohistochemical analysis were carried out to validate the screened proteins in 27 IBS-D patients and 27 controls. Thirdly, high-performance liquid chromatography (HPLC) was further carried out to determine ATP concentration in the mucosa of colon between 10 IBS-D patients and 8 controls. Comparisons between 2 groups were performed by Student's t-test or Mann-Whitney U-test. RESULTS: Twelve differentially expressed proteins were screened out. The α-enolase (ENOA) in the sigmoid colon (0.917 ± 0.007 vs. 1.310 ± 0.100, t = 2.643, P = 0.017) and caecum (0.765 ± 0.060 vs. 1.212 ± 0.122, t = 2.225, P = 0.023), Isobutyryl-CoA dehydrogenase (ACAD8) in the sigmoid colon (1.127 ± 0.201 vs. 1.497 ± 0.392, t = 7.093, P = 0.008) of the IBS-D group were significantly lower while acetyl-CoA acetyltransferase (CT) in the caecum (2.453 ± 0.422 vs. 0.931 ± 0.652, t = 8.363, P = 0.015) and ATP synthase subunit d (ATP5H) in the sigmoid (0.843 ± 0.042 vs. 0.631 ± 0.042, t = 8.613,P = 0.007) of the IBS-D group was significantly higher, compared with the controls. The ATP concentration in the mucosa of the sigmoid colon in IBS-D group was significantly lower than that of control group (0.470 [0.180, 1.360] vs. 5.350 [2.230, 7.900], U = 55, P < 0.001). CONCLUSIONS Many proteins related to energy metabolism presented differential expression patterns in the mucosa of colon of the IBS-D patients. The abnormalities in energy metabolism may be involved in the pathogenesis of IBS which deserves more studies to elucidate.
Adenosine Triphosphate ; metabolism ; Adult ; Blotting, Western ; Colon ; metabolism ; pathology ; Diarrhea ; enzymology ; metabolism ; pathology ; Electrophoresis, Gel, Two-Dimensional ; Energy Metabolism ; genetics ; physiology ; Female ; Humans ; Immunohistochemistry ; Intestinal Mucosa ; enzymology ; metabolism ; pathology ; Irritable Bowel Syndrome ; enzymology ; metabolism ; pathology ; Male ; Mass Spectrometry ; Middle Aged ; Proteome ; metabolism

PURPOSE: Postinfectiously irritable bowel syndrome (PI-IBS) develops in 3-30% of individuals with bacterial gastroenteritis. Recent studies demonstrated increases in inflammatory components in gut mucosa of PI-IBS patients even after complete resolution of infection. We aimed to investigate histological changes in colon and rectum of PI-IBS subjects after long term period of infection. MATERIALS AND METHODS: We recruited PI-IBS subjects who had been diagnosed IBS after complete resolution of enteritis caused by shigellosis outbreak 3 years earlier. We compared unmatched four groups, PI-IBS (n = 4), non PI-IBS (n = 7), D-IBS (n = 7, diarrhea predominant type) and healthy controls (n = 10). All of them underwent colonoscopic biopsy at three areas, including descending colon (DC), sigmoid colon (SC) and rectum, which were assessed for 5-hydroxytryptamine (5-HT)/peptide YY (PYY)-containing enterochromaffin (EC) cell, intraepithelial (IEL) and lamina propria T lymphocyte (CD3), CD8 lymphocytes, mast cells and CD68/calprotectin+ macrophages. RESULTS: All subjects had no structural or gross abnormalities at colonoscopy. In PI-IBS, 5-HT containing EC cells, PYY containing EC cells, IELs, CD3 lymphocytes, CD8 lymphocytes, mast cells, and CD68 + macrophages were increased compared to control (p < 0.05). In D-IBS, PYY containing EC cells, IELs, and CD3 lymphocytes were increased compared to control (p < 0.05). In PI-IBS, 5-HT containing EC cells tended to increase and PYY containing EC cells, CD8 lymphocytes, mast cells, and CD68+ macrophages were increased compared to non PI-IBS (p < 0.05). Calprotectin + marcrophages were decreased in PI-IBS, non PI-IBS and IBS compared to control. CONCLUSION: The immunoendocrine cells were sporadically increased in PI-IBS, non PI-IBS and D-IBS compared with control. Our findings in a very small number of patients suggest that mucosal inflammation may play a role in long-term PI-IBS, and that other sub-groups of IBS and larger scale studies are needed to confirm this observation.
Adult ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; CD8-Positive T-Lymphocytes/cytology ; Case-Control Studies ; Colon, Descending/pathology ; Colon, Sigmoid/pathology ; Colonoscopy ; Dysentery, Bacillary/*complications ; Enterochromaffin Cells/cytology ; Female ; Humans ; Immunohistochemistry ; Intestinal Mucosa/*pathology ; Irritable Bowel Syndrome/metabolism/*pathology ; Macrophages/cytology ; Male ; Mast Cells/cytology ; Peptide YY/metabolism ; Rectum/pathology ; Serotonin/metabolism

OBJECTIVETo investigate the changes of intestinal mucosal tight junction proteins claudin-1, -3, -4 in patients with irritable bowel syndrome (IBS), and elucidate its possible role in the bowel evacuation habit changes and formation in these patients.

METHODSWestern blotting was employed to determine tight junction protein claudin-1,-3,-4 levels in the intestinal mucosa of patients in the control group, diarrhea-predominant IBS (D-IBS) group and constipation-predominant IBS (C-IBS) group.

RESULTSCompared with the control group, D-IBS patients showed significantly decreased claudin-1 protein levels in both the small intestinal and colonic mucosae (P<0.05), whereas C-IBS patients had significantly elevated claudin-1 protein levels (P<0.05). No significant difference was found in claudin-3 protein expression in the both small intestinal and colonic mucosae between the D-IBS group and the control group (P>0.05), but claudin-3 protein level was shown to increase significantly in C-IBS patients (P<0.05). Claudin-4 protein followed the same pattern of alteration as claudin-1.

CONCLUSIONDown-regulated claudin-1 and -4 expressions can be associated with bowel evacuation habit changes and formation in patients with D-IBS, but up-regulated claudin-1, -3 and -4 expressions may relate to such bowel changes in patients with C-IBS.

Adolescent ; Adult ; Aged ; Animals ; Blotting, Western ; Case-Control Studies ; Claudin-1 ; Claudin-3 ; Claudin-4 ; Colon ; metabolism ; pathology ; Female ; Gene Expression Regulation ; Humans ; Intestinal Mucosa ; metabolism ; pathology ; Irritable Bowel Syndrome ; metabolism ; pathology ; Male ; Membrane Proteins ; metabolism ; Middle Aged ; Tight Junctions ; metabolism ; Young Adult