Ulcerative Colitis: Shanahan F

Shanahan F. · Department of Medicine, University College Cork, National University of Ireland, Cork, Ireland. · Eur J Surg Suppl. · Pubmed #16144200 No free full text.

This publication has no abstract.

Shanahan F, Quera R. · Department of Medicine, Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Ireland, UK. · Am J Gastroenterol. · Pubmed #15330892 No free full text.

This publication has no abstract.

Shanahan F. · Department of Medicine, Cork University Hospital and University College Cork, National University of Ireland, Ireland. · Aliment Pharmacol Ther. · Pubmed #12950414 links to  free full text

Abstract: Colorectal cancer (CRC) remains a feared and potentially life-threatening complication of both ulcerative colitis and Crohn's colitis. Currently, the main preventive strategy is a secondary one, i.e. surveillance colonoscopy usually after 8 years of disease duration, when the risk for neoplasia begins to increase. Despite its widespread acceptance, dysplasia and cancer surveillance is unproven in terms of reducing mortality or morbidity and there is a remarkable lack of uniformity in the manner in which it is practised. In this review article, the pitfalls of dysplasia surveillance are summarized and the need for novel chemopreventive and perhaps pharmabiotic approaches for prevention are highlighted.

Cashman KD, Shanahan F. · Department of Food & Nutritional Sciences, University College, Cork, Ireland. · Eur J Gastroenterol Hepatol. · Pubmed #12840670 No free full text.

Abstract: Inflammatory bowel disease (IBD) is a chronic inflammatory process, the aetiology of which is complex and probably multi-factorial. Nutrition has been proposed to be an important aetiological factor for IBD. The present review critically examines the relationship between components of the diet (such as sugar, fat, fibre, fruit and vegetables, and protein) and IBD, including ulcerative colitis and Crohn's disease. In addition, it investigates the possible role of infant feeding practices in the development of IBD.

Shanahan F. · Dept. of Medicine, University College Cork, National University of Ireland. · Scand J Gastroenterol Suppl. · Pubmed #12797679 No free full text.

Abstract: Therapeutic manipulation of gut flora with probiotics promises to be a useful strategy for several disorders, including infectious, inflammatory and neoplastic conditions. However, there are large gaps in the knowledge of the normal flora and of the optimal use of probiotic products. At present, there is no reliable in vitro predictor of in vivo efficacy of putative probiotics. Indeed, probiotic performance should be defined in the context of the disease indication for which it is intended. This will require rigorous prospective clinical trials. In addition, guidelines for routine clinical use of probiotics are confounded by insufficient data on optimum strain selection, dose, delivery vehicle and monitoring. Before the promise can be fulfilled, problems and potential pitfalls with probiotic therapy need resolution.

Marteau P, Seksik P, Shanahan F. · Gastroenterology Department, European Hospital Georges Pompidou, AP-HP & Paris V University, France. · Best Pract Res Clin Gastroenterol. · Pubmed #12617882 No free full text.

Abstract: In this chapter we summarize the clinical and experimental data which indicate that bacteria, especially from the endogenous microflora, play a role in the pathogenesis of Crohn's disease, ulcerative colitis and pouchitis. We review the clinical trials, focusing on randomized controlled trials which used antibiotics or probiotics to treat situations of IBD or prevent recurrence, and we discuss the future of this approach.

Shanahan F. · Department of Medicine, Clinical Sciences Building, Cork University Hospital, Wilton, Ireland. · Br J Nutr. · Pubmed #12215176 No free full text.

Abstract: Probiotic therapy is attracting the renewed interest of clinicians and basic investigators from a variety of traditional research disciplines. While the theoretical rationale for modifying the commensal flora of the gastrointestinal tract in specific circumstances appears sound and requires scientific pursuit, the field of probiotics has been clouded by exaggerated claims from some quarters. In general, many of the claims for therapeutic efficacy have not been well substantiated, but the field is now poised for evaluation within the realm of evidence-based medicine. Alterations in commensal bacterial flora within the gastrointestinal tract are associated with susceptibility to pathogens such as Clostridium difficile and there is persuasive evidence that the normal flora may participate in the pathogenesis of inflammatory bowel disease and other chronic diseases in genetically susceptible individuals. This has prompted various strategies to fortify or otherwise modify the enteric flora by dietary supplements containing probiotic formulations. Detailed comparisons of probiotic performance amongst different bacterial strains have not been performed in vivo in man or under clinical trial conditions, and the level of scientific characterisation of individual organisms has been variable. In addition, it cannot be assumed that the same probiotic is equally suitable for all individuals. Moreover, the heterogeneity of clinical disorders such as Crohn's disease and ulcerative colitis implies that strain-specific properties may be required for subset-specific categories of patients. While cocktails of probiotics offer convenience, therapeutic progress may require clarification of the mechanism of probiotic action and may be delayed until individual bacterial components have been rigorously studied. More importantly, the full potential of therapeutic manipulation of the enteric flora with probiotics or other strategies may not be optimally realised until the composition and metabolic activities of the normal flora are better understood.

Dunne C, O'Mahony L, Murphy L, Thornton G, Morrissey D, O'Halloran S, Feeney M, Flynn S, Fitzgerald G, Daly C, Kiely B, O'Sullivan GC, Shanahan F, Collins JK. · Department of Microbiology, and the National Food Biotechnology Center, University College, Cork, Ireland. · Am J Clin Nutr. · Pubmed #11157346 links to  free full text

Abstract: The enteric flora comprises approximately 95% of the total number of cells in the human body and can elicit immune responses while protecting against microbial pathogens. However, the resident bacterial flora of the gastrointestinal tract may also be implicated in the pathogenesis of diseases such as inflammatory bowel disease (ulcerative colitis and Crohn disease). The objectives of the Probiotic Research Group based at University College Cork were to isolate and identify lactic acid bacteria exhibiting beneficial probiotic traits, such as bile tolerance in the absence of deconjugation activity, acid resistance, adherence to host epithelial tissue, and in vitro antagonism of pathogenic microorganisms or those suspected of promoting inflammation. To isolate potentially effective probiotic bacteria, we screened the microbial population adhering to surgically resected segments of the gastrointestinal tract (the environment in which they may subsequently be reintroduced and required to function). In total, 1500 bacterial strains from resected human terminal ilea were assessed. From among these organisms, Lactobacillus salivarius subsp. salivarius strain UCC118 was selected for further study. In mouse feeding trials, milk-borne L. salivarius strain UCC118 could successfully colonize the murine gastrointestinal tract. A human feeding study conducted in 80 healthy volunteers showed that yogurt can be used as a vehicle for delivery of strain UCC118 to the human gastrointestinal tract with considerable efficacy in influencing gut flora and colonization. In summary, we developed criteria for in vitro selection of probiotic bacteria that may reflect certain in vivo effects on the host such as modulation of gastrointestinal tract microflora.

Shanahan F. · Department of Medicine, University College Cork, National University of Ireland. · Inflamm Bowel Dis. · Pubmed #10833070 No free full text.

Abstract: Most conventional forms of drug therapy suppress or modify the host immunoinflammatory response and neglect the other contributor to disease pathogenesis-the environmental microflora. Probiotics are live microbial food ingredients that alter the enteric microflora and have a beneficial effect on health. The rationale for using probiotics in IBD is mainly based on evidence from human studies and experimental animal models implicating intestinal bacteria in the pathogenesis of these disorders. The relationship between bacteria and intestinal inflammation is complex and does not appear to reflect a simple cause and effect. Similarly, the field of probiotics is complex and in need of rigorous research. Until the indigenous flora are better characterized and mechanisms of probiotic action defined, the promise of probiotics in IBD is unlikely to be fulfilled. Because of strain-specific variability and clinical and therapeutic heterogeneity within Crohn's disease and ulcerative colitis, it cannot be assumed that a given probiotic is equally suitable for all individuals. Although preliminary results of probiotic therapy in animal models and humans with ulcerative colitis and pouchitis have been encouraging, their efficacy in treatment or maintenance of remission of Crohn's disease remains to be clarified. However, the circumstantial evidence for some form of biotherapeutic modification of the enteric flora in Crohn's disease seems compelling. In the future, probiotics may offer a simple adjunct to conventional therapy with the emphasis on diet shifting from one of nutritional replenishment alone to a more functional role.

Shanahan F, Bernstein CN. · Department of Medicine, Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland. · Curr Opin Gastroenterol. · Pubmed #19349861 No free full text.

Abstract: PURPOSE OF REVIEW: Epidemiologic studies in inflammatory bowel disease (IBD) include assessments of disease burden and evolving patterns of disease presentation. Although it is hoped that sound epidemiologic studies provide aetiological clues, traditional risk factor-based epidemiology has provided limited insights into either Crohn's disease or ulcerative colitis etiopathogenesis. In this update, we will summarize how the changing epidemiology of IBD associated with modernization can be reconciled with current concepts of disease mechanisms and will discuss studies of clinically significant comorbidity in IBD. RECENT FINDINGS: The increased frequency of IBD, which has been consistently observed as society becomes developed or modernized, may be linked with changes in the gastrointestinal microbiota which, in turn, may affect the development of the immune system and influence the risk of inflammatory diseases. Although extra-intestinal disease associations have long been recognized to be linked to IBD, there is a disturbing increase in comorbidity with Clostridium difficile-associated disease, arterial and venous thromboembolism and abnormalities of cervical cytology. These have important implications in an era of increased use of immunomodulatory drugs. SUMMARY: Advances in understanding the basic biology of IBD with rapidly emerging therapeutic strategies have prompted a shift in traditional epidemiologic approaches away from risk factor anthologies toward rapprochement with disease mechanisms and pursuit of changing patterns of comorbidity of clinical relevance.

Clayton EM, Rea MC, Shanahan F, Quigley EM, Kiely B, Hill C, Ross RP. · Alimentary Pharmabiotic Centre at Moorepark Food Research Centre, Teagasc, Fermoy Co., Cork, Ireland. · Am J Gastroenterol. · Pubmed #19319128 No free full text.

Abstract: OBJECTIVES: Comorbidity with Clostridium difficile may cause diagnostic delay in newly presenting inflammatory bowel disease (IBD) patients, trigger relapse in established disease, confound therapies, and serve as an indicator of an underlying defect in innate immunity. Retrospective analyses have suggested community acquisition; to address this we conducted a prospective analysis of C. difficile carriage in IBD patients using molecular methods specifically in an outpatient setting. METHODS: Recruited participants had long-standing diagnoses of ulcerative colitis (n = 64) and Crohn's disease (n = 58), were in clinical remission, and had no recent exposure to antibiotics, corticosteroids, immunomodulatory drugs or recent hospitalization. Isolates were cultured from stools and confirmed by 16S sequencing. The antibiotic susceptibilities of the isolates were tested followed by further strain characterization by toxinotyping, ribotyping, and pulsed-field gel electrophoresis (PFGE). RESULTS: The frequency of toxigenic C. difficile was higher in IBD patients than in healthy volunteers at 8.2 and 1.0%, respectively (P = 0.02 Fisher's exact test). All strains belonged to toxinotype 0 with rare subtypes of this group noted in five isolates and represented by an altered repressor genotype. Patients harbored a diverse range of toxigenic ribotype groups, including those previously associated with C. difficile-associated disease (CDAD) (R015, R005, and R020) and the rarer types R062, R050, and R003. Interestingly, common nosocomial groups were not identified. The considerable nonclonal distribution of distinct strains was further demonstrated by PFGE genomic fingerprinting. None of the study subjects experienced a clinical episode of CDAD during a 6-month period of follow-up. CONCLUSIONS: Detection of C. difficile is increased in IBD outpatients in remission, and strain diversity is consistent with community acquisition from a multitude of sources.

Scanlan PD, Shanahan F, Marchesi JR. · Alimentary Pharmabiotic Centre, National University of Ireland, University College Cork, Cork, Ireland. · BMC Microbiol. · Pubmed #18492229 links to  free full text

Abstract: BACKGROUND: The incidence and diversity of human methanogens are insufficiently characterised in the gastrointestinal tract of both health and disease. A PCR and clone library methodology targeting the mcrA gene was adopted to facilitate the two-fold aim of surveying the relative incidence of methanogens in health and disease groups and also to provide an overview of methanogen diversity in the human gastrointestinal tract. RESULTS: DNA faecal extracts (207 in total) from a group of healthy controls and five gastrointestinal disease groups were investigated. Colorectal cancer, polypectomised, irritable bowel syndrome and the control group had largely equivalent numbers of individuals positive for methanogens (range 45-50%). Methanogen incidence in the inflammatory bowel disease groups was reduced, 24% for ulcerative colitis and 30% for Crohn's disease. Four unique mcrA gene restriction fragment length polymorphism profiles were identified and bioinformatic analyses revealed that the majority of all sequences (94%) retrieved from libraries were 100% identical to Methanobrevibacter smithii mcrA gene. In addition, mcrA gene sequences most closely related to Methanobrevibacter oralis and members of the order Methanosarcinales were also recovered. CONCLUSION: The mcrA gene serves as a useful biomarker for methanogen detection in the human gut and the varying trends of methanogen incidence in the human gut could serve as important indicators of intestinal function. Although Methanobrevibacter smithii is the dominant methanogen in both the distal colon of individuals in health and disease, the diversity of methanogens is greater than previously reported. In conclusion, the low incidence of methanogens in Inflammatory Bowel Disease, the functionality of the methanogens and impact of methane production in addition to competitive interactions between methanogens and other microbial groups in the human gastrointestinal tract warrants further investigation.

Shanahan F. · Alimentary Pharmabiotic Centre, Cork University Hospital, University College Cork, National University of Ireland, Department of Medicine, Cork, Ireland. · Curr Gastroenterol Rep. · Pubmed #17511913 No free full text.

This publication has no abstract.

Marchesi JR, Holmes E, Khan F, Kochhar S, Scanlan P, Shanahan F, Wilson ID, Wang Y. · Alimentary Pharmabiotic Centre and Department of Microbiology, University College Cork, College Road, Cork, Ireland. · J Proteome Res. · Pubmed #17269711 No free full text.

Abstract: Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) have a major impact on the health of individuals and populations. Accurate diagnosis of inflammatory bowel disease (IBD) at an early stage, and correct differentiation between Crohn's disease (CD) and ulcerative colitis (UC), is important for optimum treatment and prognosis. We present here the first characterization of fecal extracts obtained from patients with CD and UC by employing a noninvasive metabonomics approach, which combines high resolution 1H NMR spectroscopy and multivariate pattern recognition techniques. The fecal extracts of both CD and UC patients were characterized by reduced levels of butyrate, acetate, methylamine, and trimethylamine in comparison with a control population, suggesting changes in the gut microbial community. Also, elevated quantities of amino acids were present in the feces from both disease groups, implying malabsorption caused by the inflammatory disease or an element of protein losing enteropathy. Metabolic differences in fecal profiles were more marked in the CD group in comparison with the control group, indicating that the inflammation caused by CD is more extensive in comparison with UC and involves the whole intestine. Furthermore, glycerol resonances were a dominant feature of fecal spectra from patients with CD but were present in much lower intensity in the control and UC groups. This work illustrates the potential of metabonomics to generate novel noninvasive diagnostics for gastrointestinal diseases and may further our understanding of disease mechanisms.

Gilman J, Shanahan F, Cashman KD. · Department of Food and Nutritional Sciences, University College, Cork, Ireland. · Aliment Pharmacol Ther. · Pubmed #16573803 No free full text.

Abstract: BACKGROUND: The pathogenesis of inflammatory bowel disease-associated osteopenia may be related to pathological rates of bone turnover; however, the literature shows mixed results. AIM: To compare bone biomarkers in inflammatory bowel disease patients (Crohn's disease: n = 68, and ulcerative colitis: n = 32, separately) with age- and sex-matched healthy controls. SUBJECTS: Patients and controls were recruited from Cork University Hospital and Cork City area, respectively. RESULTS: Relative to that in their respective controls, Crohn's disease (n = 47) and ulcerative colitis (n = 26) patients (i.e. excluding supplement users) had significantly (P < 0.05-0.001) higher serum undercarboxylated osteocalcin (by 27% and 63%, respectively) and bone-specific alkaline phosphatase (by 15% and 21%, respectively) and urinary Type I collagen cross-linked N-telopeptides concentrations (by 87% and 112%, respectively). Relative to that in their respective controls, Crohn's disease and ulcerative colitis patients had significantly (P < 0.01) lower serum total osteocalcin (by 20% and 42%, respectively) and 25-hydroxyvitamin D (by 37% and 42%, respectively), while serum parathyroid hormone levels were similar. In the combined patient group (n = 100), undercarboxylated osteocalcin was positively associated with bone markers. CONCLUSIONS: Both Crohn's disease and ulcerative colitis patients have altered bone turnover relative to that in healthy controls.

Kelly P, Maguire PB, Bennett M, Fitzgerald DJ, Edwards RJ, Thiede B, Treumann A, Collins JK, O'Sullivan GC, Shanahan F, Dunne C. · Department of Medicine, Cork Cancer Research Centre and Alimentary Pharmabiotic Centre at the National University of Ireland, Cork, Ireland. · FEMS Microbiol Lett. · Pubmed #16214296 No free full text.

Abstract: Lactobacillus salivarius subsp. salivarius UCC118 is a probiotic bacterium that was originally isolated from human intestinal tissues and was subsequently shown in a pilot study to alleviate symptoms associated with mild-moderate Crohn's disease. Strain UCC118 can adhere to animal and human intestinal tissue, and to both healthy and inflamed ulcerative colitis mucosa, irrespective of location in the gut. In this study, an enzymatic technique has been combined with proteomic analysis to correlate bacterial growth phase with the presence of factors present in the cell wall of the bacterium. Using PAGE electrophoresis, it was determined that progression from lag to log to stationary growth phases in vitro correlated with increasing prominence of an 84kD protein associated with in vitro adherence ability. Isolated proteins from the 84kD band region were further separated by two-dimensional electrophoresis, resolving this band into 20 individual protein spots at differing isoelectric points. The protein moieties were excised, trypsin digested and subjected to tandem mass spectrometry. The observed proteins are analogous to those reported to be associated with the Listeria monocytogenes cell-wall proteome, and include DnaK, Ef-Ts and pyruvate kinase. These data suggest that at least some of the beneficial attributes of probiotic lactobacilli, and in particular this strain, may be due to nonpathogenic mimicry of pathogens and potentially be mediated through a form of attenuated virulence.

Duffy M, O'Mahony L, Coffey JC, Collins JK, Shanahan F, Redmond HP, Kirwan WO. · Department of Surgery, Cork University Hospital, Ireland. · Dis Colon Rectum. · Pubmed #12068199 No free full text.

Abstract: PURPOSE: Ileal pouch-anal anastomosis remains the "gold standard" in surgical treatment of ulcerative colitis and familial adenomatous polyposis. Pouchitis occurs mainly in patients with a background of ulcerative colitis, although the reasons for this are unknown. The aim of this study was to characterize differences in pouch bacterial populations between ulcerative colitis and familial adenomatous pouches. METHODS: After ethical approval was obtained, fresh stool samples were collected from patients with ulcerative colitis pouches (n = 10), familial adenomatous polyposis (n = 7) pouches, and ulcerative colitis ileostomies (n = 8). Quantitative measurements of aerobic and anaerobic bacteria were performed. RESULTS: Sulfate-reducing bacteria were isolated from 80 percent (n = 8) of ulcerative colitis pouches. Sulfate-reducing bacteria were absent from familial adenomatous polyposis pouches and also from ulcerative colitis ileostomy effluent. Pouch Lactobacilli, Bifidobacterium, Bacteroides sp, and Clostridium perfringens counts were increased relative to ileostomy counts in patients with ulcerative colitis. Total pouch enterococci and coliform counts were also increased relative to ileostomy levels. There were no significant quantitative or qualitative differences between pouch types when these bacteria were evaluated. CONCLUSIONS: Sulfate-reducing bacteria are exclusive to patients with a background of ulcerative colitis. Not all ulcerative colitis pouches harbor sulfate-reducing bacteria because two ulcerative colitis pouches in this study were free of the latter. They are not present in familial adenomatous polyposis pouches or in ileostomy effluent collected from patients with ulcerative colitis. Total bacterial counts increase in ulcerative colitis pouches after stoma closure. Levels of Lactobacilli, Bifidobacterium, Bacteroides sp, Clostridium perfringens, enterococci, and coliforms were similar in both pouch groups. Because sulfate-reducing bacteria are specific to ulcerative colitis pouches, they may play a role in the pathogenesis of pouchitis.

O'Riordan A, Shanahan F. · No affiliation provided · Gastroenterology. · Pubmed #11375971 No free full text.

This publication has no abstract.

Coffey JC, Bennett MW, Wang JH, O'Connell J, Neary P, Shanahan F, Redmond HP, Kirwan WO. · Department of Academic Surgery, Cork University Hospital, Cork, Ireland. · J Surg Res. · Pubmed #11368534 No free full text.

Abstract: INTRODUCTION: Ileal pouch-anal anastomosis (IPAA) remains the gold standard for patients with refractory ulcerative colitis. Pouchitis causes considerable morbidity in 40% of patients with IPAA. This study examined the role of increased epithelial apoptosis in the etiology of pouchitis. METHODS: Following ethical approval pouch biopsies taken from patients with a history of pouchitis were compared with age-matched controls from patients who were pouchitis free. Apoptosis was detected immunohistochemically using a monoclonal antibody (M30) and terminal deoxyribonucleotidyl transferase (TDT)-mediated dUTP-digoxigenin end labeling (TUNEL). Villous atrophy was assessed histologically and correlated with levels of apoptosis. Epithelial Fas-ligand (L) was also assessed immunohistochemically. RESULTS: A significant increase in TUNEL staining was seen at the epithelial but not at the lamina propria level for known pouchitis patients versus controls (0.091 vs 0.035; P < 0.01). Similarly, epithelial M30 immunoreactivity (0.225 vs 0.082; P < 0.05) and villous atrophy (0.035 vs 0.10; P < 0.05) were significantly increased in pouches with previous pouchitis when compared with normal pouches. Upregulation of Fas-L expression was characteristic of this epithelium. Mononuclear cells were strongly positive for Fas-L. Increased epithelial levels of apoptosis correlated with increased levels of villous atrophy. CONCLUSIONS: Our data suggest a role for elevated Fas-Fas-L (CD95-CD95L)-mediated epithelial apoptosis in the etiology of pouchitis. Increased levels of villous atrophy may result from increased apoptosis and thereby predispose to infection by otherwise apathogenic organisms.

Shanahan F. · Department of Medicine, Cork University Hospital, Cork, Ireland. · Science. · Pubmed #10979858 No free full text.

Abstract: In developed countries as many as two individuals in every thousand suffer from inflammatory bowel disease (ulcerative colitis and Crohn's disease). In his Perspective, Shanahan discusses a new therapeutic approach to treating these conditions in which bacteria normally found in the gut are engineered to produce the anti-inflammatory cytokine interleukin-10 and then are fed as probiotics to mice with these disorders (Steidler et al.).

Goode T, O'Connell J, Anton P, Wong H, Reeve J, O'Sullivan GC, Collins JK, Shanahan F. · Department of Medicine, National University of Ireland, Cork, Ireland. · Gut. · Pubmed #10940277 links to  free full text

Abstract: BACKGROUND: Substantial evidence implicates the neuropeptide substance P (SP) in mucosal immunoinflammatory responses. Autoradiographic studies have suggested a disturbance in SP receptor expression in inflammatory bowel disease (IBD). AIMS: Because of technical limitations such as poor cellular resolution with autoradiography, we used molecular methods to specifically localise the cellular expression of the neurokinin-1 receptor (NK-1R) in IBD colon, and to quantitate NK-1R mRNA expression levels therein. METHODS: In situ hybridisation and immunohistochemistry were used to localise NK-1R mRNA and protein, respectively, in normal, ulcerative colitis (UC), and Crohn's disease (CD) colonic resections. NK-1R mRNA expression levels of normal, UC, and CD mucosal biopsies were quantitated by competitive reverse transcription-polymerase chain reaction. RESULTS: NK-1R expression was localised to lamina propria mononuclear cells, epithelium, submucosal vasculature, smooth muscle, and myenteric plexus of normal and IBD colon. No ectopic NK-1R expression was observed in IBD. However, we found increased numbers of NK-1R expressing lymphoid cells in IBD tissue, aberrant negative epithelial expression of NK-1R in UC, and increased expression of NK-1R in CD myenteric plexus. Quantitation of NK-1R mRNA expression in IBD colonic mucosal biopsies revealed marked upregulation of NK-1R mRNA levels compared with non-inflamed mucosal expression levels (p<0.01). CONCLUSIONS: This report demonstrates the strategic localisation and upregulation of NK-1R expression in IBD colon, and thereby suggests the involvement of substance P in the pathophysiological symptoms of IBD.