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This study investigated immune profiles of ulcerative colitis (UC) patients and irritable bowel syndrome (IBS) patients and healthy individuals and showed that inflammatory mechanisms leading to IBS-like symptoms in UC may be different from the mechanisms leading to IBS., Background Inflammatory mechanisms of ulcerative colitis (UC) and irritable bowel syndrome (IBS) may overlap or are part of different spectrums. However, potential links between inflammation and IBS-like symptoms in these patient groups are still unclear. The aim of this study was to determine if the systemic inflammatory protein (SIP) profiles differ between UC patients, with presence of inflammation or in remission with or without IBS-like symptoms, and IBS patients. Methods Serum from patients with active UC (UCA), UC patients in remission with or without IBS-like symptoms (UCR + IBS, UCR-IBS), IBS patients (IBS), and healthy subjects (HS) was analyzed using the ProSeek Multiplex Inflammation kit, which detects 92 proteins. Results The exploratory cohort consisted of 166 subjects (UCA, n = 40; UCR-IBS, n = 45; UCR + IBS, n = 20; IBS, n = 40; HS, n = 21). Systemic inflammatory protein profiles separated UC from non-UC (HS and IBS) patients in multivariate analysis, revealing caspase 8, axin 1, sulfotransferase 1A1, and tumor necrosis factor superfamily member 14 as the variables most important to clustering. Although minor differences were detected between UCR + IBS and UCR-IBS, SIP profiles discriminated UCA from UCR, and interleukin (IL) 17C, IL17A, chemokine ligand 9, and transforming growth factor–α characterized active inflammation. SIP profiles weakly discriminated HS from IBS, although fibroblast growth factor 21 and IL6 serum levels were higher in IBS. Results were confirmed in a validation cohort (UCA, n = 15; UCR + IBS, n = 9; IBS, n = 14). Conclusions SIP profiles distinguish UC patients from IBS patients, irrespective of inflammation or IBS-like symptoms, suggesting that inflammatory mechanisms of the diseases are part of different spectrums.

BACKGROUND The clinical disease course of ulcerative colitis (UC) varies substantially between individuals and can currently not be reliably predicted. The gut microbiota and the host's immune defense are key players for gut homeostasis and may be linked to disease outcome. The aim of this study was to determine fecal microbiota composition and mucosal antibacterial response profile in untreated patients with newly diagnosed UC and the impact of these factors on disease course. METHODS Stool samples and intestinal biopsies were obtained from therapy-naive newly diagnosed patients with UC. Patients were defined to have mild or moderate/severe disease course assessed by disease activity during the 3 years follow-up. Fecal microbiota was analyzed by the GA-map Dysbiosis test (n = 18), and gene expression in intestinal biopsies was analyzed by RT Profiler polymerase chain reaction array (n = 13) and real-time polymerase chain reaction (n = 44). RESULTS At the time of diagnosis of UC, the fecal microbiota composition discriminated between patients with mild versus moderate/severe disease course. Also, the mucosal antibacterial gene expression response profile differed between patients with mild versus moderate/severe disease course with bactericidal/permeability-increasing protein (BPI) being most important for the discrimination. Mucosal bactericidal/permeability-increasing protein gene expression at diagnosis was higher in patients with mild versus moderate/severe disease course when confirmed in a larger patient cohort (P = 0.0004, n = 44) and was a good predictor for the number of flares during the 3 years follow-up (R = 0.395, P < 0.0001). CONCLUSIONS In patients with newly diagnosed UC, fecal microbiota composition and mucosal antibacterial response profile, especially bactericidal/permeability-increasing protein, are linked to disease course.

BACKGROUND Gastrointestinal symptoms (GI) compatible with irritable bowel syndrome (IBS) are common in patients with ulcerative colitis (UC) in remission. The causes of these symptoms remain to be clarified. Our aim was to investigate prevalence and factors associated with IBS-like symptoms in patients with UC in deep remission. METHODS We included 298 patients with UC and used Mayo score, sigmoidoscopy, and fecal calprotectin to define deep remission versus active disease. Presence of IBS-like symptoms according to the Rome III criteria, severity of GI, extraintestinal and psychological symptoms, stress levels, and quality of life were measured with validated questionnaires. Serum cytokines and high-sensitive C-reactive peptide were determined. RESULTS The criteria for deep remission was fulfilled by 132 patients (44%) and 24 of these fulfilled the Rome III criteria for IBS (18%). Patients with UC in deep remission with IBS-like symptoms had comparable levels of GI symptoms, non-GI somatic symptoms, and quality of life as patients with active UC. The patients with UC in deep remission with IBS-like symptoms had similar levels of fecal calprotectin as patients in deep remission without IBS-like symptoms (18 versus 31 μg/g, P = 0.11), but higher levels of serum cytokines (interleukin [IL]-1β, IL-6, IL-13, IL-10 and IL-8, P < 0.05) and higher levels of anxiety (P < 0.001), depression (P = 0.02) and perceived stress (P = 0.03). CONCLUSIONS IBS-like symptoms in patients with UC in deep remission are common, but not as prevalent as previously reported. Poor psychological well-being and increased serum cytokine levels, but not colonic low-grade inflammation, were associated with IBS-like symptoms.

Background The clinical course of ulcerative colitis (UC) is unpredictable. The need for reliable biomarkers to reflect disease severity and predict disease course is therefore large. We investigated whether cytokines in mucosal tissue and serum reflect clinical disease severity at the onset of UC and predict the future disease course. Methods We prospectively monitored 102 patients from the onset of UC during 3 years, and they were followed up yearly for clinical and biochemical disease severity. Rectal biopsies were obtained from healthy controls and patients with UC. Serum and stool samples were obtained from patients with UC. Total mRNA from biopsies was analyzed with real-time PCR. Cytokine levels in serum were determined using Luminex or ELISA. Results Mucosal mRNA expression of IL-17A was 99.8 times higher while IFN-γ and IL-13 expression was increased 12.4 and 6.7 times, respectively, in patients relative to controls. Serum IL-17A correlated with clinical disease severity at the onset. Also, contrary to a number of other parameters, serum IL-17A at the onset predicted the clinical and biochemical course of the disease, as reflected by the Mayo score, number × severity of flares, and fecal calprotectin levels, respectively, during 3 years after the onset of the disease. None of these associations were found with mucosal cytokines at the onset. Conclusions Serum IL-17A levels of treatment-naive patients with UC reflect clinical disease severity at the onset of the disease and also predicted the disease course over the following 3 years. Thus, serum IL-17A may be valuable in the clinical management of patients with UC at the onset of the disease.

Background The clinical course of ulcerative colitis (UC) is unpredictable. During recent years, the ability of fecal biomarkers to predict relapse in inflammatory bowel disease has been evaluated. The objective of this study was to assess fecal calprotectin (FC) as a predictor of disease recurrence in patients with new onset of UC. Methods Sixty-nine patients were included. After the initial treatment, patients were followed up after 3 months and then yearly for 3 years. The prognostic role of FC 3 months after the initial therapy was evaluated. Results The FC levels 3 months after the diagnosis were higher in patients experiencing a relapsing disease course compared with those with a mild disease course during 1 year (median, 263; interquartile range [IQR], 100-634 μg/g versus median, 102; IQR, 38-225 μg/g; P = 0.009) and 3 years of follow-up (median, 280; IQR, 102-622 μg/g versus median, 118; IQR, 39-219 μg/g; P = 0.01). The area under the receiver operating characteristic curves using calprotectin to predict a relapsing disease course during 1 year and 3 years were 0.69 (95% confidence interval, 0.56-0.82) and 0.70 (95% confidence interval, 0.57-0.83), respectively. In the Kaplan-Meier survival analysis, a FC level >262 μg/g was associated with an increased risk of a relapsing disease course during the study period (P = 0.003). In logistic regression analysis, only FC and age were found to be independent predictors of having a relapsing disease course. Conclusions Levels of FC 3 months after the initial therapy in patients with new onset of UC predict the disease course over the following years, and they are of value in the clinical management of these patients.

Background: Factors determining the extension and degree of inflammation in the colonic mucosa of patients with ulcerative colitis (UC) are largely unknown, but CD4 + CD25 high regulatory T cells (Tregs) have been implicated to play an important role in suppressing inflammation. Therefore, the aims of this study were to determine whether colonic Tregs have suppressive effects on colonic effector T cells in UC and to analyze the association between segmental colonic Treg distribution and disease activity. Materials and Methods: The suppressive activity of colonic CD4 + CD25 high Tregs from patients with active UC was determined in coculture assays measuring proliferation and cytokine production. The frequency of Tregs and the expression of the Treg marker FOXP3 were analyzed with flow cytometry and RT-PCR in isolated cells and the whole mucosa from patients with active and inactive disease, as well as healthy mucosa. Results: Colonic CD4 + CD25 high T cells from patients with UC suppressed the proliferation and cytokine secretion of colonic effector CD4 + T cells. Healthy controls but not patients with UC had lower Treg frequencies in the sigmoid than in the ascending colon. Patients with UC with active disease had increased frequency of colonic Tregs. The frequency of Tregs was positively correlated with colonic disease activity and serum C-reactive protein. Conclusions: Colonic CD4 + CD25 high Tregs are able to suppress colonic effector T cell activity in vitro, and the Treg frequency in the inflamed intestine increases with disease activity in patients with active UC. This suggests that Tregs may be outnumbered by other inflammatory cells or that their suppressive activity may be influenced by the in vivo environment.