Authors: Kristjansson G, Venge P, Wanders A, Loof L, Hallgren R.

Institution: Department of Medical Sciences, University of Uppsala, University Hospital of Uppsala, 75185 Uppsala, Sweden. gudjon.kristjansson@medsci.uu.se

Background: There is a clear need for a rapid, simple, safe, and sensitive method of determining the type and intensity of inflammation in the gut mucosa in clinical practice. In this study, we have evaluated the potential of a new method, the mucosal patch technique, in patients with and without apparent gut inflammation, as assessed by conventional diagnostic procedures. Subjects and

Methods: The technique tested is based on the idea that inflammatory mediators released from the rectal mucosa can be absorbed by and then extracted from cellulose patches brought into contact with the mucosa by use of an instrument with an inflatable balloon. Measurements were performed in healthy controls (n = 16) and in patients with active (n = 19) and inactive ulcerative colitis (UC, n = 8), collagen colitis (CC, n = 12), coeliac disease (n = 13), and irritable bowel syndrome (IBS, n = 13).

Results: Inflammatory mediators from neutrophils (myeloperoxidase (MPO)) and eosinophils (eosinophil cationic protein (ECP)) were increased on average 300- and 10-fold, respectively, in patients with active UC compared with healthy controls and were correlated with the endoscopic score. Patients with inactive UC, CC, coeliac disease, and IBS exhibited no endoscopic signs of inflammation. These patient groups had significantly lower levels of MPO and ECP than the active UC group but showed on average a four- to sevenfold increase in MPO compared with healthy controls.

Conclusion: The mucosal patch technique was well tolerated by patients and easily applied by the investigator. Pronounced neutrophil and eosinophil involvement in UC was demonstrated. With the high sensitivity of the technique, low degree mucosal neutrophil activation could also be quantified in patients with CC and UC in clinical remission. The finding of increased neutrophil involvement in patients with IBS contributes to the pathophysiological ideas of this disease.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15542519&query_hl=12&itool=pubmed_docsum

Authors: Barbara G, De Giorgio R, Stanghellini V, Cremon C, Corinaldesi R.

Institution: Department of Internal Medicine and Gastroenterology, University of Bologna, Bologna, Italy. gbarbara@med.unibo.it

Summary: Attention has been directed to the putative role of low grade mucosal inflammation in irritable bowel syndrome (IBS) on the basis of evidence showing that some patients with IBS have an increased number of inflammatory cells in the colonic and ileal mucosa.

Previous episodes of infectious enteritis, genetic factors, undiagnosed food allergies, and changes in bacterial microflora may all play a role in promoting and perpetuating this low grade inflammatory process. Human and animal studies support the concept that inflammation may perturb gastrointestinal reflexes and activate the visceral sensory system even when the inflammatory response is minimal and confined to the mucosa.

Thus abnormal neuroimmune interactions may contribute to the altered gastrointestinal physiology and hypersensitivity that underlies IBS. A brief review of the human and animal studies that have focused on the putative role of intestinal inflammation and infections in the pathogenesis of IBS is given.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12077063&dopt=Abstract

Authors: Weston AP, Biddle WL, Bhatia PS, Miner PB Jr.

Institution: Department of Medicine, University of Kansas Medical Center, Kansas City.

Comment: Terminal ileal biopsies were prospectively obtained and stained specifically for mast cells in 20 patients with irritable bowel syndrome (IBS) and 15 controls. The number of terminal ileal mast cells per high powered field (MC/HPF) (mean +/- SEM) was 23.3 +/- 3.1 for IBS and 6.8 +/- 1.1 for controls (P = 0.0001).

The diarrhea IBS subgroup had the greatest number of MC/HPF. No correlation was found between terminal ileal mucosal mast cell counts (MMCC) and the number of Manning criteria present or the functional bowel disease score (r = 0.06 and r = -0.31, respectively).

We conclude that terminal ileal MMCC are significantly elevated in a majority of patients with IBS. The mast cell may be responsible for the altered visceral perception found in the gastrointestinal tract in patients with IBS. The poor correlation of the MMCC to the clinical features of IBS may be the result of the dynamic state of the mast cell.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=8359068&query_hl=25

Authors: O'Sullivan M, Clayton N, Breslin NP, Harman I, Bountra C, McLaren A, O'Morain CA.

Institution: Adelaide & Meath Hospitals, Trinity College Dublin, Ireland.

Comment: Mast cells (MC) release potent mediators which alter enteric nerve and smooth muscle function and may play a role in the pathogenesis of the irritable bowel syndrome (IBS).

The aim of this study was to determine if MC were increased in the colon of IBS patients compared to controls. Biopsy specimens were obtained from the caecum, ascending colon, descending colon and rectum of 28 patients: 14 IBS (Rome criteria); seven normal; and seven inflammatory controls.

Tissue was stained immunohistochemically using a monoclonal mouse antibody for human mast cell tryptase (AA1). Tissue area occupied by tryptase-positive MC (volume density of mast cells) was quantified by image analysis…

Apart from MC, there was no evidence of increased cellular infiltrate in the IBS group. MC were significantly increased in the caecum of IBS patients compared to controls.

The multiple effects of the intestinal mast cell alone, or as a participant of a persistent inflammatory response, may be fundamental to the pathogenesis of IBS.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11012945&dopt=Abstract

Authors: Barbara G, Stanghellini V, De Giorgio R, Cremon C, Cottrell GS, Santini D, Pasquinelli G, Morselli-Labate AM, Grady EF, Bunnett NW, Collins SM, Corinaldesi R.

Institution: Departmentof Internal Medicine and Gastroenterology, and CRBA, University of Bologna, Italy. gbarbara@med.unibo.it

Background and Aims: The mechanisms underlying abdominal pain perception in irritable bowel syndrome (IBS) are poorly understood. Intestinal mast cell infiltration may perturb nerve function leading to symptom perception. We assessed colonic mast cell infiltration, mediator release, and spatial interactions with mucosal innervation and their correlation with abdominal pain in IBS patients.

Results: Thirty-four out of 44 IBS patients (77%) showed an increased area of mucosa occupied by mast cells as compared with controls (9.2% +/- 2.5% vs. 3.3 +/- 0.8%, respectively; P < 0.001)...

Mast cells located within 5 microm of nerve fibers were 7.14 +/- 3.87/field vs. 2.27 +/- 1.63/field in IBS vs. controls (P < 0.001). Only mast cells in close proximity to nerves were significantly correlated with severity and frequency of abdominal pain/discomfort (P < 0.001 and P = 0.003, respectively).

Conclusions: Colonic mast cell infiltration and mediator release in proximity to mucosal innervation may contribute to abdominal pain perception in IBS patients.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=14988823&query_hl=20

Authors: Park CH, Joo YE, Choi SK, Rew JS, Kim SJ, Lee MC.

Institution: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.

Comment: Mast cells (MC) may be one factor influencing the response of visceral afferent nerves to mechanical and chemical stimuli. The aim of this study was to evaluate the degree of infiltration and activity of colonic MC in irritable bowel syndrome (IBS).

Biopsy specimens were obtained from the cecum and rectum of 14 diarrhea predominant IBS and 14 normal controls. Electron microscopy was used to determine the number of intact and degranulated colonic MC and to quantify these separately according to the distance between MC and enteric nerves.

An increased number of MC in both cecum and rectum in the IBS group in comparison with the control group was demonstrated (p<0.05). Activated MC in close proximity to enteric nerves were significantly increased in both cecum and rectum of the IBS group compared to control group (p<0.005). In addition, activated MC were significantly increased in close proximity to the nerves compared to those in the remote area in both cecum and rectum of the IBS group (p<0.0001).

MC were significantly increased and activated in both cecum and rectum of the IBS group compared to controls. MC may play a role in the gut sensory hypersensitivity of IBS.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12692417&query_hl=18

Authors: Tornblom H, Lindberg G, Nyberg B, Veress B.

Institution: Karolinska Institutet Department of Medicine, Huddinge University Hospital, Stockholm, Sweden. hans.tornblom@gastro.hs.sll.se

Background and Aims: Irritable bowel syndrome (IBS) is regarded as a functional bowel disorder. Few studies have looked for histopathologic changes in the gut and only then in biopsy specimens from intestinal mucosa. Because bowel function is governed mainly by nerve plexuses in the bowel wall, we have investigated full-thickness bowel biopsy specimens in patients with severe IBS.

Results: Ten patients (2 males, 8 females) were studied. In 9 patients, we found low-grade infiltration of lymphocytes in the myenteric plexus. Lymphocytes had peri- and intraganglionic location. The mean number of lymphocytes per ganglion ranged from 1.9 to 7.1 per patient, with an overall mean of 3.4.

No intraganglionic lymphocytes were found in the control group and only a few periganglionic lymphocytes (mean, 0.2). Four patients had concomitant intraepithelial lymphocytosis. Neuron degeneration was evident in 6 of 9 patients with and 1 patient without ganglionic lymphocyte infiltration.

Conclusions: Our findings indicate that inflammation and neuronal degeneration in the myenteric plexus are involved in the pathogenesis of IBS.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12454854&dopt=Abstract

Authors: Yehuda Ringel, MD Douglas A. Drossman, MD

A detailed discussion of the irritable bowel syndrome and inflammation.

Infection and Inflammation: Stephen M. Collins[study link below] provided a comprehensive review of the evidence suggesting the need to consider infection and inflammation in the pathogenesis of some patients with IBS. He presented data from clinical studies showing the development of IBS symptoms following acute gastroenteritis (ie, postinfectious [PI] IBS) and a higher than expected prevalence of IBS symptoms among patients with inflammatory bowel disease that was in remission.

Additionally, data from animal studies demonstrated that altered gut physiology can persist even after the infection and associated inflammation have resolved. Furthermore, studies of mucosal biopsies, from both human and animal models, have shown increased inflammatory cells and inflammatory mediators in patients with IBS and in previously sensitized/stressed animals.

Finally, some recent studies have shown proximity between nerve trunks and the inflammatory cells, suggesting a local neuroimmune interaction that may contribute to the pathogenesis of IBS. With respect to the latter, several key studies presented during these meeting proceedings provided some supportive evidence relating the role of infection and inflammation to IBS.

Study link: http://www.medscape.com/viewarticle/434527

Authors: Premysl Bercik, MD*, Elena F. Verdu, MD, PhD, Stephen M. Collins, MD, FRCP

Institution: Intestinal Disease Research Program and Division of Gastroenterology, McMaster University, 1200 Main Street West, HSC 3N49C, Hamilton, Ontario L8N 3Z5, Canada.

Summary: The authors believe that inflamed bowel disease and at least a subset of irritable bowel syndrome patients exist at two ends of the same spectrum of pathophysiology, which involves immune activation and inflammation.

This is prompted by the observation that IBS symptoms may precede IBD, which reflects gut dysfunction generated by subclinical inflammation. It also has been observed that IBS occurs in patients in remission from IBD. This concept is underpinned by results of basic scientific studies in animal models showing that immune activation and inflammation restricted to the mucosal compartment result in profound changes in neuromuscular function that may persist after recovery of the mucosa.

Emerging evidence shows similarities in genotype between IBD and a subset of IBS patients; polymorphisms of genes that encode cytokine secretion may result in an imbalance of pro- and counter inflammatory signals. This in turn would lead to inefficient down-regulation of inflammatory responses and promote low-grade inflammation.

It is a matter of the severity of inflammation that separates IBD and this IBS subset, and this may reflect additional genetic abnormalities or greater exposure to environmental factors in the case of IBD. This prompts the question as to whether IBD is more common in patients with IBS, and there is some evidence to support this.

Study link: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15862932&dopt=Citation