***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Introduction Immune activation has been reported in the mucosa of IBS patients with diarrhoea ( IBS-D ) , and some small studies have suggested that mesalazine may reduce symptoms . We performed a double-blind , r and omised  placebo-controlled trial of 2 g mesalazine twice daily versus placebo for 3 months in patients with Rome III criteria IBS-D. Primary outcome was daily average stool frequency during weeks 11–12 ; secondary outcomes were abdominal pain , stool consistency , urgency and satisfactory relief of IBS symptoms . Methods Participants were r and omised after a 2-week baseline stool diary . All participants completed a 12-week stool diary and at the end of each week recorded the presence of ‘ satisfactory relief of IBS symptoms ’ . Results 136 patients with IBS-D ( 82 women , 54 men ) were r and omised , 10 patients withdrew from each group . Analysis by intention to treat showed the daily average stool frequency during weeks 11 and 12 were mean ( SD ) , 2.8 ( 1.2 ) in mesalazine and 2.7 ( 1.9 ) in the placebo group with no significant group difference , ( 95 % CI ) 0.1 ( −0.33 to 0.53 ) , p=0.66 . Mesalazine did not improve abdominal pain , stool consistency nor percentage with satisfactory relief  compared with placebo during the last two-weeks follow-up . Conclusions This study does not support any clinical ly meaningful benefit or harm of mesalazine compared with placebo in unselected patients with IBS-D. More precise subtyping based on underlying disease mechanisms is needed to allow more effective targeting of treatment in IBS . Trial registration number NCT01316718 Background : Post‐infectious irritable bowel syndrome is associated with increased serotonin‐containing enterochromaffin cells and lymphocytes in rectal biopsies . Animal studies have suggested that steroids reduce the lymphocyte response and suppress some of the post‐infectious changes in neuromuscular function Certain therapeutic microbes , including Bifidobacteria infantis ( B. infantis ) 35624 exert beneficial immunoregulatory effects by mimicking commensal-immune interactions ; however , the value of these effects in patients with non-gastrointestinal inflammatory conditions remains unclear . In this study , we assessed the impact of oral administration of B. infantis 35624 , for 6‒8 weeks on inflammatory biomarker and plasma cytokine levels in patients with ulcerative colitis ( UC ) ( n = 22 ) , chronic fatigue syndrome ( CFS ) ( n = 48 ) and psoriasis ( n = 26 ) in three separate r and omized , double-blind , placebo-controlled interventions . Additionally , the effect of B. infantis 35624 on immunological biomarkers in healthy subjects ( n = 22 ) was assessed . At baseline , both gastrointestinal ( UC ) and non-gastrointestinal ( CFS and psoriasis ) patients had significantly increased plasma levels of C-reactive protein ( CRP ) and the pro-inflammatory cytokines tumor necrosis factor α ( TNF-α ) and interleukin-6 ( IL-6 ) compared with healthy volunteers . B. infantis 35624 feeding result ed in reduced plasma CRP levels in all three inflammatory disorders compared with placebo . Interestingly , plasma TNF-α was reduced in CFS and psoriasis while IL-6 was reduced in UC and CFS . Furthermore , in healthy subjects , LPS-stimulated TNF-α and IL-6 secretion by peripheral blood mononuclear cells ( P BMC s ) was significantly reduced in the B. infantis 35624-treated groups compared with placebo following eight weeks of feeding . These results demonstrate the ability of this microbe to reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions . In conclusion , these data show that the immunomodulatory effects of the microbiota in humans are not limited to the mucosal immune system but extend to the systemic immune system BACKGROUND & AIMS Both psychological and mucosal changes ( increased enterochromaffin [ EC ] cells and T lymphocytes ) have been associated with postinfectious irritable bowel syndrome ( PI-IBS ) . However , previous studies have been underpowered to determine the relative importance of these changes in predicting the development of PI-IBS . Our aim was to prospect ively determine the relative importance of both psychological and histologic factors in the development of PI-IBS after Campylobacter infection . METHODS Question naires detailing psychological and bowel symptoms were sent to 1977 patients 3 months after infection . Twenty-eight patients with new-onset PI-IBS , 28 age- and sex-matched patient controls who were asymptomatic after infection , and 34 healthy volunteers underwent rectal biopsy  , which was assessed for serotonin-containing EC cells , mast cells , and lamina propria T lymphocytes . RESULTS PI-IBS , predominantly of the diarrhea-predominant subtype , occurred in 103 of 747 ( 13.8 % ) of those infected . EC cell counts per high-power field ( hpf ) were higher in patients with PI-IBS ( 35.8 + /- 1.2 ) compared with patient controls ( 30.6 + /- 1.9 ; P = 0.022 ) and volunteers ( 29.1 + /- 1.8 ; P = 0.006 ) . Lamina propria T lymphocytes per hpf were higher in patients with PI-IBS ( 127.1 + /- 8.7 ) and patient controls ( 113.4 + /- 6.2 ) in contrast to healthy volunteers ( 97.1 + /- 5.7 ) ( P = 0.006 and P = 0.058 , respectively ) . Anxiety , depression , and fatigue were significantly increased in patients with PI-IBS compared with patient controls . Multivariate analysis indicated that increased EC cell counts and depression were equally important predictors of developing PI-IBS ( relative risk , 3.8 and 3.2 for each st and ard deviation increase in respective values ) . CONCLUSIONS Both increased EC cells and depression are important independent predictors of developing PI-IBS Objective Low- grade intestinal inflammation plays a role in the pathophysiology of IBS . In this trial , we aim ed at evaluating the efficacy and safety of mesalazine in patients with IBS . Design We conducted a phase 3 , multicentre , tertiary setting , r and omised , double-blind , placebo-controlled trial in patients with Rome III confirmed IBS . Patients were r and omly assigned to either mesalazine , 800 mg , or placebo , three times daily for 12 weeks , and were followed for additional 12 weeks . The primary efficacy endpoint was satisfactory relief of abdominal pain/discomfort for at least half of the weeks of the treatment period . The key secondary endpoint was satisfactory relief of overall IBS symptoms . Supportive analyses were also performed classifying as responders patients with a percentage of affirmative answers of at least 75 % or > 75 % of time . Results A total of 185 patients with IBS were enrolled from 21 centres . For the primary endpoint , the responder patients were 68.6 % in the mesalazine group versus 67.4 % in the placebo group ( p=0.870 ; 95 % CI −12.8 to 15.1 ) . In explorative analyses , with the 75 % rule or > 75 % rule , the percentage of responders was greater in the mesalazine group with a difference over placebo of 11.6 % ( p=0.115 ; 95 % CI −2.7 % to 26.0 % ) and 5.9 % ( p=0.404 ; 95 % CI −7.8 % to 19.4 % ) , respectively , although these differences were not significant . For the key secondary endpoint , overall symptoms improved in the mesalazine group and reached a significant difference of 15.1 % versus placebo ( p=0.032 ; 95 % CI 1.5 % to 28.7 % ) with the > 75 % rule . Conclusions Mesalazine treatment was not superior than placebo on the study primary endpoint . However , a subgroup of patients with IBS showed a sustained therapy response and benefits from a mesalazine therapy . Trial registration number ClincialTrials.gov number , NCT00626288 Background Mast cell activation is thought to be involved in visceral hypersensitivity , one of the main characteristics of the irritable bowel syndrome ( IBS ) . A study was therefore undertaken to investigate the effect of the mast cell stabiliser ketotifen on rectal sensitivity and symptoms in patients with IBS . Methods 60 patients with IBS underwent a barostat study to assess rectal sensitivity before and after 8 weeks of treatment . After the initial barostat , patients were r and omised to receive ketotifen or placebo . IBS symptoms and health-related quality of life were scored . In addition , mast cells were quantified and spontaneous release of tryptase and histamine was determined in rectal biopsies and compared with biopsies from 22 age- and gender-matched healthy volunteers . Results Ketotifen but not placebo increased the threshold for discomfort in patients with IBS with visceral hypersensitivity . This effect was not observed in normosensitive patients with IBS . Ketotifen significantly decreased abdominal pain and other IBS symptoms and improved quality of life . The number of mast cells in rectal biopsies and spontaneous release of tryptase were lower in patients with IBS than in healthy volunteers . Spontaneous release of histamine was mostly undetectable but was slightly increased in patients with IBS compared with healthy volunteers . Histamine and tryptase release were not altered by ketotifen . Conclusions This study shows that ketotifen increases the threshold for discomfort in patients with IBS with visceral hypersensitivity , reduces IBS symptoms and improves health-related quality of life . Whether this effect is secondary to the mast cell stabilising properties of ketotifen or H1 receptor antagonism remains to be further investigated . Trial Registration Number NTR39 , IS RCT N22504486 Abstract Background and aims . There is evidence for low- grade inflammation in the pathophysiology of post-infectious irritable bowel syndrome ( IBS ) . We assessed the degree of sub clinical intestinal mucosal inflammation in diarrhea-predominant IBS ( IBS-D ) in a tropical setting . Material and methods . In a prospect i ve study over 1 year , we investigated 49 patients with IBS-D ( cases ; median age 34 years ( range 18–59 ) ; M : F 36:13 ) , diagnosed on Rome III criteria . 14 individuals with a family history of colon cancer ( median age 46.5 years ( range 23–56 ) ; M : F 6:8 ) were selected as controls . Stools of cases and controls were tested for calprotectin .  During colonoileoscopy , serial biopsies were obtained . Mucosal mast cells , neutrophils , eosinophils and lymphocytes/plasma cell infiltrate were quantified . Tissue expression of IL-8 and IL-10 was assessed in biopsies by semi-quantitative RT-PCR . Results . A history suggestive of an episode of infectious diarrhea ( ID ) was present in 16/49 cases and 0/14 controls ( p = 0.013 ) . In cases , there were significantly more mucosal mast cells in the ileum and all segments of colon and significantly more eosinophils in the cecum . Tissue expression of IL-8 was significantly higher and IL-10 significantly lower in cases compared with controls ( target/st and ard cDNA ratio , median ( range ) IL-8 : 1.25 ( 0.75–2 ) vs. 0.85 ( 0.63–1.3 ) , p < 0.0001 , Mann – Whitney U test ; IL-10 : 0.33 ( 0–0.63 ) vs. 0.55 ( 0.5–0.7 ) , p < 0.0001 ) . There was a significant inverse correlation between IL-8 and IL-10 expression ( Pearson correlation , ( - ) 0.509 ; p < 0.01 ) . Conclusion . There was evidence of sub clinical intestinal mucosal inflammation in patients with IBS-D. The finding of increased eosinophils is novel , and may be of special relevance to IBS-D in the tropics Background and Aims : The aim of the present study was to evaluate proinflammatory and anti-inflammatory cytokine levels in children with irritable bowel syndrome ( IBS ) . Patients and Methods : Thirty-five children with IBS ( 17 diarrhea-predominant , 7 constipation-predominant , and 11 mixed type ) and 25 healthy children as healthy controls ( HCs ) were enrolled . All of the participants completed a question naire recording the duration , severity , and associated academic and social influences . Peripheral blood mononuclear cells were isolated and cultured for 24 hours with and without 1 or 5 ng/mL Escherichia coli lipopolysaccharide ( LPS ) .  Cytokine production including tumor necrosis factor-α ( TNF-α ) , interleukin (IL)-6 , and IL-10 was measured using enzyme-linked immunosorbent assays . Results : Children with IBS revealed lower baseline 
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RESULTS Levels of interleukin (IL)-10 tended to be decreased and those of IL-6 , IL-8 , tumor necrosis factor-α and IL-1β increased in the systemic circulation in IBS , while in the mucosa , IL-10 was decreased and IL-8 , mast cells , enterochromaffin cells and CD3 + T lymphocytes were increased .