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Irritable Bowel Syndrome: HELP
Articles by Fergus Shanahan
Based on 19 articles published since 2008

Between 2008 and 2019, F. Shanahan wrote the following 19 articles about Irritable Bowel Syndrome.
+ Citations + Abstracts
1 Editorial Editorial: probiotics and IBS - where are we now? 2014

Moran, C / Shanahan, F. ·Department of Medicine, Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland. ·Aliment Pharmacol Ther · Pubmed #25040745.

ABSTRACT: -- No abstract --

2 Editorial The neglected spectrum of diverticular-related disorders. 2013

Shanahan, Fergus. ·Department of Medicine and Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland. ·Clin Gastroenterol Hepatol · Pubmed #23602826.

ABSTRACT: -- No abstract --

3 Review Manipulation of the microbiota for treatment of IBS and IBD-challenges and controversies. 2014

Shanahan, Fergus / Quigley, Eamonn M M. ·Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland; Department of Medicine, University College Cork, National University of Ireland, Cork, Ireland. Electronic address: F.Shanahan@ucc.ie. · Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland; Division of Gastroenterology and Hepatology, Houston Methodist, Houston, Texas. ·Gastroenterology · Pubmed #24486051.

ABSTRACT: There is compelling rationale for manipulating the microbiota to treat inflammatory bowel diseases (IBDs). Although studies of animal models of intestinal inflammation produced promising results, trials in humans have been disappointing. In contrast to IBD, the role of the microbiota in the development of irritable bowel syndrome (IBS) only recently has been considered, but early stage results have been encouraging. As pharmaceutical companies develop fewer truly novel agents for treatment of these disorders, consumers seek safer, long-term strategies to deal with chronic symptoms. We assess the rationale for modulating the microbiota for treatment of IBD and IBS, and discuss whether current concepts are simplistic and overstated or simply under-researched. Are claims exaggerated and expectations unrealistic? Difficulties with microbiota terminology and technologies, as well as differences among patients and the heterogeneity of these diseases, pose additional challenges in developing microbiota-based therapies for IBD and IBS.

4 Review The colonic microbiota in health and disease. 2013

Shanahan, Fergus. ·Department of Medicine, Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Ireland. f.shanahan@ucc.ie ·Curr Opin Gastroenterol · Pubmed #23041677.

ABSTRACT: PURPOSE OF REVIEW: Diverse research interests have converged on the gut microbiota because of its contribution to immune development, mucosal homeostasis and to the pathogenesis of a diversity of intestinal and extraintestinal disorders. Recent landmark findings are addressed here. RECENT FINDINGS: The impact of lifestyle, including dietary changes and antibiotics, on the microbiota has been mechanistically linked with disease risk. Microbial, immune and metabolic signalling are mutually interactive, with each of these being regulated by diet. Although changes in the microbiota have been found in several disorders and may have important therapeutic implications, some components of the commensal microbiota may behave like pathogens (pathobionts) depending on the context and host susceptibility. SUMMARY: Advances in understanding host-microbe interactions in the gut continue apace, they are relevant to a diversity of infectious, inflammatory, neoplastic and metabolic disorders and are poised for clinical translation.

5 Review The colonic microbiota and colonic disease. 2012

Shanahan, Fergus. ·Department of Medicine and Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Dublin, Ireland. F.Shanahan@ucc.ie ·Curr Gastroenterol Rep · Pubmed #22941733.

ABSTRACT: The colonic ecosystem differs from that in the proximal gut in several important respects. The colonic microbiota represents the largest population of microbes colonizing humans from birth. Constraints on bacterial numbers, composition, and interaction with the host involve not only the innate and acquired immune system, but also the colonic mucin structure. While the microbiota provides beneficial protective, trophic, nutritional, and metabolic signals for the host, it may become a risk factor for disease depending on context and host susceptibility. Technological advances including DNA-based high-throughput compositional analysis have linked changes in the indigenous microbiota with several human diseases. In some instances, these findings have the potential to serve as new biomarkers of risk of disease. In this overview, recent advances are focused upon in relation to irritable bowel syndrome, inflammatory bowel disease, and colon cancer. The possibility that the therapeutic solution to some of these disorders may reside within the microbiota will also be addressed.

6 Review Role of radiologic imaging in irritable bowel syndrome: evidence-based review. 2012

O'Connor, Owen J / McSweeney, Sean E / McWilliams, Sebastian / O'Neill, Siobhan / Shanahan, Fergus / Quigley, Eamonn M M / Maher, Michael M. ·Department of Radiology, Cork University Hospital and Alimentary Pharmabiotic Centre, University College Cork, Wilton, Cork, Ireland. ·Radiology · Pubmed #22156992.

ABSTRACT: PURPOSE: To critically evaluate the current literature in an effort to establish the current role of radiologic imaging (computed tomography, magnetic resonance imaging, ultrasonography [US], fluoroscopy, conventional film radiography) in irritable bowel syndrome (IBS). MATERIALS AND METHODS: The term "irritable bowel syndrome" was used to search Clinical Evidence, UpToDate, Cochrane Library, TRIP, and National Institute for Health and Clinical Excellence databases and the American College of Physicians Journal Club and Evidence-Based Medicine online. PubMed was searched by using medical subject headings ("irritable bowel syndrome;" "colonic diseases, functional;" "diagnosis;" "colonography;" "computed tomographic (CT)") and the dates January 1, 1985 to July 1, 2010. Appraisal was independently performed by two reviewers who followed the Oxford Centre for Evidence Based Medicine practice criteria. RESULTS: No systematic review (SR) specifically examined radiologic imaging in IBS; however, in the secondary literature, five relevant SRs or guidelines partially addressed this topic. A PubMed search identified 1451 articles, 111 of which at least partially addressed radiologic imaging. Of these, seven valid articles (two SRs and five primary research articles) were identified. The five primary research articles examined either colonic investigations (colonoscopy and barium enema examination) (n=5) or US (n=2) or both (n=2). Structural disease found infrequently in patients with IBS-type symptoms included diverticulosis, colorectal cancer, celiac disease, inflammatory bowel disease, and ovarian cancer. The incidence of structural disease in patients with concerning symptoms was low. CONCLUSION: Although widely used, there is a surprising paucity of evidence guiding radiologic imaging in IBS. Radiologic imaging may not be required in patients with IBS without potentially concerning symptoms but should be considered where such symptoms exist, and choice of imaging study should be influenced by predominant symptoms. Definitive recommendations must await further research.

7 Article Cognitive performance in irritable bowel syndrome: evidence of a stress-related impairment in visuospatial memory. 2014

Kennedy, P J / Clarke, G / O'Neill, A / Groeger, J A / Quigley, E M M / Shanahan, F / Cryan, J F / Dinan, T G. ·Alimentary Pharmabiotic Centre, University College Cork, Ireland. · Department of Psychology, University of Hull, UK. ·Psychol Med · Pubmed #23985155.

ABSTRACT: BACKGROUND: Central nervous system (CNS) dysfunction is a prominent feature of the functional gastrointestinal (GI) disorder, irritable bowel syndrome (IBS). However, the neurobiological and cognitive consequences of key pathophysiological features of IBS, such as stress-induced changes in hypothalamic-pituitary-adrenal (HPA)-axis functioning, is unknown. Our aim was to determine whether IBS is associated with cognitive impairment, independently of psychiatric co-morbidity, and whether cognitive performance is related to HPA-axis function. METHOD: A cross-sectional sample of 39 patients with IBS, a disease control group of 18 patients with Crohn's disease (CD) in clinical remission and 40 healthy age- and IQ-matched control participants were assessed using the Paired Associates Learning (PAL), Intra-Extra Dimensional Set Shift (IED) and Spatial Working Memory (SWM) tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) and a computerized Stroop test. HPA-axis function was determined by measuring the cortisol awakening response (CAR). RESULTS: IBS patients exhibited a subtle visuospatial memory deficit at the PAL six- pattern stage (p = 0.03), which remained after psychiatric co-morbidity was controlled for (p = 0.04). Morning cortisol levels were lower in IBS (p = 0.04) and significantly associated with visuospatial memory performance within IBS only (p = 0.02). CONCLUSIONS: For the first time, altered cognitive function on a hippocampal-mediated test of visuospatial memory, which was related to cortisol levels and independent of psychiatric co-morbidity, has been identified in IBS. Visuospatial memory impairment may be a common, but currently neglected, component of IBS. Further elucidation of the nature of this impairment may lead to a greater understanding of the underlying pathophysiology of IBS, and may provide novel therapeutic approaches.

8 Article Bifidobacterium breve with α-linolenic acid and linoleic acid alters fatty acid metabolism in the maternal separation model of irritable bowel syndrome. 2012

Barrett, Eoin / Fitzgerald, Patrick / Dinan, Timothy G / Cryan, John F / Ross, R Paul / Quigley, Eamonn M / Shanahan, Fergus / Kiely, Barry / Fitzgerald, Gerald F / O'Toole, Paul W / Stanton, Catherine. ·Alimentary Pharmabiotic Centre, Biosciences Institute, University College Cork, Cork, Ireland. ·PLoS One · Pubmed #23185248.

ABSTRACT: The aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15) were orally gavaged with either B. breve DPC6330 (10(9) microorganisms/day) alone or in combination with 0.5% (w/w) linoleic acid & 0.5% (w/w) α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11) in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (p<0.05). Administration of B. breve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11) in adipose tissue and palmitoleic acid in the prefrontal cortex (p<0.05), whereas feeding B. breve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (p<0.05) compared with the NS un-supplemented controls. Administration of B. breve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (p<0.01) and α-linolenic acid in adipose tissue (p<0.001), whereas feeding B. breve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (p<0.05), and α-linolenic acid in adipose tissue (p<0.001). B. breve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated rats significantly modified the palmitoleic acid, arachidonic acid and docosahexaenoic acid contents in tissues. The effect was not observed in non-separated animals.

9 Article Carriage of Clostridium difficile in outpatients with irritable bowel syndrome. 2012

Clayton, Evelyn M / Rea, Mary C / Shanahan, Fergus / Quigley, Eamonn M M / Kiely, Barry / Ross, R Paul / Hill, Colin. ·Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland. ·J Med Microbiol · Pubmed #22580916.

ABSTRACT: Irritable bowel syndrome (IBS) is a common, typically chronic and sometimes disabling gastrointestinal condition of uncertain aetiology. Recently, a variety of links to gastrointestinal infections have been described including the onset of IBS following exposure to enteric pathogens and an apparent predisposition to gastrointestinal infection. The prevalence of Clostridium difficile in a population of IBS outpatients (n = 87) in the absence of established risk factors for the acquisition of C. difficile infection was examined. Overall, 5.7 % of patients (n = 5) carried culturable C. difficile and 4.6 % (n = 4) of isolates were toxigenic, belonging to toxinotype group 0, compared with 1.1 % (n = 1) for the healthy control group (n = 88). These isolates were members of toxigenic PCR ribotype groups 005 and 050 (IBS group) and 062 (control group) and were identified further as three individual strains by PFGE. Although no significant difference was observed between IBS patients and healthy volunteers, these findings support the concept that a subpopulation of IBS patients may be susceptible to gastrointestinal infection.

10 Article Increased risk of miscarriage and ectopic pregnancy among women with irritable bowel syndrome. 2012

Khashan, Ali S / Quigley, Eamonn M M / McNamee, Roseanne / McCarthy, Fergus P / Shanahan, Fergus / Kenny, Louise C. ·Anu Research Centre, Department of Obstetrics and Gynecology, University College Cork, National University of Ireland, Cork, Ireland. ·Clin Gastroenterol Hepatol · Pubmed #22373726.

ABSTRACT: BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is the most commonly diagnosed gastrointestinal condition and is most prevalent in women of reproductive age. We investigated the effects of IBS on risk for adverse outcomes from pregnancy. METHODS: We conducted a cohort study by using the United Kingdom General Practice Research Database. The study cohort consisted of 100,000 women selected by stratified random sampling from all women with a diagnosis of pregnancy from January 1, 1990, to December 31, 2008. Those with a recorded diagnosis of IBS before pregnancy were identified (n = 26,543). Outcome measures were spontaneous miscarriage, ectopic pregnancy, preeclampsia, and stillbirth. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between IBS and pregnancy outcomes were estimated by using logistic regression adjusted for several potential confounders. RESULTS: Of women diagnosed with IBS before pregnancy, 6578 (7%) had a spontaneous miscarriage, 741 (0.74%) had an ectopic pregnancy, 425 (0.43%) developed preeclampsia, and 217 (0.22%) had a stillbirth. Maternal IBS was associated with a moderately increased risk of miscarriage (OR, 1.21; 95% CI, 1.13-1.30) and ectopic pregnancy (OR, 1.28%; 95% CI, 1.06-1.55). There did not appear to be an association between IBS and preeclampsia (OR, 1.09; 95% CI, 0.85-1.39) or stillbirth (OR, 1.00; 95% CI, 0.69-1.44). CONCLUSIONS: IBS, a common disorder in women of reproductive age, appears to increase the risk of miscarriage and ectopic pregnancy. These findings indicate the importance of prenatal care for women with IBS.

11 Article Differential expression of toll-like receptors in patients with irritable bowel syndrome. 2011

Brint, Elizabeth K / MacSharry, John / Fanning, Aine / Shanahan, Fergus / Quigley, Eamonn M M. ·Department of Pathology, University College Cork, National University of Ireland, and Alimentary Pharmabiotic Centre, Cork University Hospital, Cork, Ireland. e.brint@ucc.ie ·Am J Gastroenterol · Pubmed #21102570.

ABSTRACT: OBJECTIVES: The pathogenesis of irritable bowel syndrome (IBS) is poorly understood. One contributory factor may be low-grade mucosal inflammation, perhaps initiated by the microbiota. Toll-like receptors (TLRs) are a family of pathogen-recognition receptors of the innate immune system. The aim of this study was to evaluate the potential involvement of TLRs in IBS to further understand the involvement of the innate immune system in this complex disorder. METHODS: The expression of TLRs was investigated in colonic biopsy samples obtained from 26 IBS patients and compared with 19 healthy controls. Protein expression of TLR4, TLR7, and TLR8 was confirmed by immunofluorescence and alterations in the TLR4 protein were confirmed by western blot. RESULTS: Quantitative reverse transcriptase-PCR showed increased levels of TLR4 (P≤0.001) and TLR5 (P=0.0013) and decreased levels of TLR7 (P≤0.001) and TLR8 (P=0.0019) in IBS patients. CONCLUSIONS: Our results support the presence of an immune engagement between the microbiota and the host in IBS; an interaction that involves innate immunity and could generate a low-grade inflammatory response. These findings could also offer an additional biomarker of the disease or a disease subset.

12 Article Plasma cytokine profiles in females with irritable bowel syndrome and extra-intestinal co-morbidity. 2010

Scully, Paul / McKernan, Declan P / Keohane, John / Groeger, David / Shanahan, Fergus / Dinan, Timothy G / Quigley, Eamonn M M. ·Alimentary Pharmabiotic Centre, University College Cork, Ireland. ·Am J Gastroenterol · Pubmed #20407431.

ABSTRACT: OBJECTIVES: Irritable bowel syndrome (IBS) is a functional disorder that is associated with a number of extra-intestinal co-morbidities and a pro-inflammatory profile. This study was designed to examine the cytokine profile among a group of IBS patients with the extra-intestinal co-morbidities fibromyalgia, premenstrual dysmorphic disorder, and chronic fatigue syndrome. METHODS: In all, 100 female IBS patients with these co-morbidities, 21 IBS subjects without co-morbidity ("pure" IBS; Rome II), and 54 age-matched female controls took part in the study. Blood was drawn for measurement of the plasma cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p70, IL-13, tumor necrosis factor (TNF)α, and interferon γ. The presence of the selected extra-intestinal manifestations was assessed using standard international criteria. RESULTS: Patients with IBS have increased plasma levels of IL-6 and IL-8; those with these extra-intestinal co-morbidities were found to have, in addition, increased levels of IL-1β and TNFα. No associations were evident between cytokine profiles and the nature of the co-morbidity or number of extra-intestinal co-morbidities present. CONCLUSIONS: Although IBS is characterized by a pro-inflammatory profile featuring the pro-inflammatory cytokines IL-6 and IL-8, IBS patients with certain extra-intestinal co-morbid conditions are distinguished by additional elevations in IL-1β and TNFα.

13 Article Irritable bowel syndrome-type symptoms in patients with inflammatory bowel disease: a real association or reflection of occult inflammation? 2010

Keohane, John / O'Mahony, Caitlin / O'Mahony, Liam / O'Mahony, Siobhan / Quigley, Eamonn M / Shanahan, Fergus. ·Department of Medicine, Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland. ·Am J Gastroenterol · Pubmed #20389294.

ABSTRACT: OBJECTIVES: Do gastrointestinal symptoms in patients with inflammatory bowel disease (IBD) in apparent remission reflect the coexistence of irritable bowel syndrome (IBS) or subclinical inflammation? The aims of this study were as follows: (i) to prospectively determine the prevalence of IBS symptoms in IBD patients in remission; and (ii) to determine whether IBS symptoms correlate with levels of fecal calprotectin. METHODS: Remission was defined by physician assessment: Crohn's disease (CD) activity index IBS-like symptoms are common in patients with IBD who are thought to be in clinical remission, but abnormal calprotectin levels suggest that the mechanism in most cases is likely to be occult inflammation rather than coexistent IBS.

14 Article A molecular analysis of fecal and mucosal bacterial communities in irritable bowel syndrome. 2010

Codling, Caroline / O'Mahony, Liam / Shanahan, Fergus / Quigley, Eamonn M M / Marchesi, Julian R. ·Department of Medicine, Alimentary Pharmabiotic Centre, Cork University Hospital, Cork, Ireland. ·Dig Dis Sci · Pubmed #19693670.

ABSTRACT: PURPOSE: The objectives of this study were, firstly, to determine the diversity of the host's gut microbiota in irritable bowel syndrome (IBS) using a culture-independent method (DGGE of the 16S rRNA gene) and, secondly, to examine mucosal biopsies of IBS patients and compare them to their own fecal microbiota. METHODS: The diversity of the dominant microbiota in the fecal material of IBS patients was compared to a healthy control group. In addition, we compared the mucosal and fecal microbiota of IBS patients. RESULTS: Statistical analysis of the mean similarity data for these groups indicated a significant difference (P < 0.001) between IBS (n = 47) and healthy controls (n = 33) with significantly more variation in the gut microbiota of healthy volunteers than that of IBS patients. The average intra-individual similarity between the mucosa and luminal microbiota was 84%, which indicates that different communities were present at the two sites. This difference, however, is similar to that previously described between these two niches in control subjects. The average inter-individual similarity of the bacterial communities on the mucosa and in the lumen of IBS was not significantly different (P > 0.05). CONCLUSIONS: IBS impacts equally on both bacterial communities in the IBS host and a significant difference in the gut microbiota exists between fecal samples from IBS patients and healthy controls. The reason for this difference is unclear and various possible explanations are available, but much more work is required to determine the underlying reason for this observation.

15 Article The language of medicine: words as servants and scoundrels. 2009

Quigley, Eamonn M M / Shanahan, Fergus. ·Department of Medicine and Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland. e.quigley@ucc.ie ·Clin Med (Lond) · Pubmed #19435117.

ABSTRACT: Progress in complex disorders requires clear thinking facilitated by clear language. Clinicians and scientists occasionally become captive to inaccurate language or meaningless terminology and this generates lazy thinking and impedes progress. Has this happened in the case of the functional gastrointestinal disorders (FGIDs), in general, and irritable bowel syndrome (IBS), in particular? FGIDs and, especially IBS, are common illnesses and an important burden on healthcare resources but, in general, have suffered from a lack of progress in the development of safe and effective treatment. Among FGIDs, IBS may be the best defined but significant lapses of accuracy in terminology persist. Among other FGIDs, the situation is more serious; imprecision and lack of consistency in terminology continue to mar progress. This article reviews the chequered history of terminology in this area and concludes that removing the obfuscation generated by poor usage of language should be the first step towards understanding the pathogenesis and improving the management of these, and similar, disorders.

16 Article Tryptophan catabolism in females with irritable bowel syndrome: relationship to interferon-gamma, severity of symptoms and psychiatric co-morbidity. 2008

Fitzgerald, P / Cassidy Eugene, M / Clarke, G / Scully, P / Barry, S / Quigley Eamonn, M M / Shanahan, F / Cryan, J / Dinan Timothy, G. ·Department of Psychiatry, University College Cork, Wilton, Cork, Ireland. peter.fitzgerald@ucc.ie ·Neurogastroenterol Motil · Pubmed #18823288.

ABSTRACT: Irritable bowel syndrome (IBS) has been linked with abnormal serotonin functioning and immune activation. Tryptophan forms the substrate for serotonin biosynthesis, but it can alternatively be catabolized to kynurenine (Kyn) by the enzyme indoleamine 2,3-dioxygenase (IDO), the main inducer of which is interferon-gamma. The primary aim of this study was to test the hypothesis that IBS is associated with increased tryptophan (Trp) catabolism along the Kyn pathway due to increased IFN-gamma levels. Plasma Kyn, Trp and IFN-gamma levels were measured in 41 female IBS subjects and 33 controls. Indoleamine 2,3-dioxygenase activity was assessed using the Kyn to Trp ratio. Psychiatric co-morbidity was assessed using the Patient Health Questionnaire, and severity of IBS assessed using self-report ordinal scales. Irritable bowel syndrome subjects had increased Kyn concentrations compared with controls (P = 0.039) and there was a trend for Kyn:Trp to be increased in the IBS group (P = 0.09). There was a positive correlation between IBS severity and Kyn:Trp (r = 0.57, P < 0.001). Those with severe IBS symptoms had increased Kyn:Trp (P < 0.005) compared to those with less severe symptoms and controls, and were over twice as likely to have depression or anxiety compared to those with less severe IBS (RR = 2.2, 95% CI 1.2-3.9). No difference in IFN-gamma levels was observed between groups; however, IFN-gamma was positively correlated with Kyn:Trp in IBS (r = 0.58, P = 0.005) but not controls (r = 0.12, P = 0.5). Females with IBS have abnormal Trp catabolism. The Kyn:Trp is related to symptom severity, and those with severe IBS symptoms have increased shunting of Trp along the Kyn pathway which contributes to the abnormal serotonergic functioning in this syndrome.

17 Article Enhanced cholinergic-mediated increase in the pro-inflammatory cytokine IL-6 in irritable bowel syndrome: role of muscarinic receptors. 2008

Dinan, Timothy G / Clarke, Gerard / Quigley, Eamonn M M / Scott, Lucinda V / Shanahan, Fergus / Cryan, John / Cooney, John / Keeling, P W N. ·Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. ·Am J Gastroenterol · Pubmed #18785949.

ABSTRACT: OBJECTIVES: Irritable bowel syndrome (IBS) is a functional disorder, which has recently been linked to immune activation. We tested the hypothesis that the pro-inflammatory cytokine profile in IBS is driven by the cholinergic system and determined if the responses are mediated by muscarinic receptors. METHODS: Eighty-eight subjects took part in two studies, 37 IBS patients (Rome II), 14 depressed patients, and 37 healthy volunteers. Eighteen IBS patients had diarrhea predominant IBS, 14 were alternators, and 5 were predominantly constipated. In study 1, blood was drawn for baseline measurement of growth hormone (GH) and cytokines IL-6, IL-8, and IL-10. Pyridostigmine 120 mg was administered orally and further blood sampling took place for 180 min. In study 2, patients with IBS, depressed patients, and healthy subjects underwent the pyridostigmine test on two separate occasions with procyclidine (antimuscarinic) pre-treatment on one test occasion. Both GH and IL-6 were monitored. RESULTS: In study 1, baseline IL-6 (P= 0.003) and IL-8 levels (P= 0.001) were higher in IBS than in controls. Pyridostigmine stimulated the release of IL-6 and GH, but not IL-8 or IL-10; these responses were significantly augmented in IBS patients relative to controls. The IL-6 level following pyridostigmine administration correlated significantly with the symptom score (P < 0.01). In study 2, IL-6 rose following pyridostigmine in IBS but not depression and procyclidine blocked the rise. The GH response was abolished by procyclidine in all three groups. CONCLUSIONS: IBS and major depression are characterized by a pro-inflammatory profile, whereas IBS patients alone exhibit an exaggerated muscarinic receptor-mediated IL-6 response.

18 Article Mucosal cytokine imbalance in irritable bowel syndrome. 2008

Macsharry, John / O'Mahony, Liam / Fanning, Aine / Bairead, Emer / Sherlock, Graham / Tiesman, Jay / Fulmer, Andy / Kiely, Barry / Dinan, Timothy G / Shanahan, Fergus / Quigley, Eamonn M M. ·Alimentary Health Ltd., Cork, Ireland. ·Scand J Gastroenterol · Pubmed #18752146.

ABSTRACT: OBJECTIVE: To systematically examine mucosal biopsies for differences in cytokine gene expression and protein secretion. MATERIAL AND METHODS: The study included 59 females with irritable bowel syndrome (IBS) and 39, otherwise healthy, female volunteers presenting for colonoscopy. Colonic biopsies from subsets were studied by microarray analysis (IBS, n=9; controls, n=8), quantitative reverse transcription-polymerase chain reaction (qRT-PCR) (IBS, n=22; controls, n=21), and ex vivo biopsy culture (IBS, n=28, controls, n=10). Biopsies from patients with active colitis were used as inflammatory disease controls. RESULTS: While gene array analysis revealed extensive overlapping between controls and IBS patients, reduced expression of genes linked to chemokine function was evident among the IBS patients alone. Differential expression was confirmed by qRT-PCR or ex vivo biopsy culture for 5 out of 6 selected genes. Reduced secretion of chemokines (IL-8, CXCL-9 and MCP-1) but not pro-inflammatory cytokines (TNF-alpha, IL-6 and IL-1beta) was established on the basis of the ex vivo biopsy cultures. These findings were in marked contrast to the IBD patients who demonstrated increased production of both chemokines and pro-inflammatory cytokines. CONCLUSIONS: Despite the expected heterogeneity of the disorder, differences in mucosal chemokine signalling were evident in this cross-sectional study of IBS patients at the level of both gene expression and protein secretion, with IBS patients demonstrating a consistent deficit in the expression and secretion of chemokines known to play a critical role in mucosal defence.

19 Article Evidence of an enhanced central 5HT response in irritable bowel syndrome and in the rat maternal separation model. 2008

O'Mahony, S / Chua, A S B / Quigley, E M M / Clarke, G / Shanahan, F / Keeling, P W N / Dinan, T G. ·Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. t.dinan@ucc.ie ·Neurogastroenterol Motil · Pubmed #18194152.

ABSTRACT: Efforts to define either a biomarker for irritable bowel syndrome (IBS) or a valid animal model have proven disappointing. The aims of this study were to determine if buspirone stimulates prolactin release through the 5-hydroxytryptamine (5HT)1a receptor and whether this response is altered in patients with IBS and in the rat maternal separation model. Buspirone (30 mg) was used to stimulate prolactin release in 40 patients with IBS and in 40 healthy controls. In study 1, 10 IBS patients and 10 controls underwent pretreatment with pindolol (5HT1a antagonist) or placebo followed by buspirone. In study 2, 30 patients with IBS and 30 healthy controls had prolactin release stimulated by buspirone. Maternally separated and nonseparated rats were also treated with buspirone and prolactin monitored. Serotonin metabolites were measured together with the expression of the 5HT1a and serotonin transporter (SERT) gene. Pindolol produced a dose-dependent decrease in the buspirone prolactin response. Patients with IBS and maternally separated rats showed an exaggerated release of prolactin in response to buspirone. In the animal model, an increased turnover of 5HT was found in the brainstem together with a trend toward increased activity of the SERT gene. In conclusion altered central serotonin responses are found in both IBS and in an animal model.