Summary Background Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD). Evidence implicates disturbances of the gastrointestinal microbiota in their pathogenesis. Aim To perform a systematic review and meta‐analysis to examine the efficacy of probiotics in IBD. Methods MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (until November 2016). Eligible randomised controlled trials (RCTs) recruited adults with UC or CD, and compared probiotics with 5‐aminosalicylates (5‐ASAs) or placebo. Dichotomous symptom data were pooled to obtain a relative risk (RR) of failure to achieve remission in active IBD, or RR of relapse of disease activity in quiescent IBD, with 95% confidence intervals (CIs). Results The search identified 12 253 citations. Twenty‐two RCTs were eligible. There was no benefit of probiotics over placebo in inducing remission in active UC (RR of failure to achieve remission=0.86; 95% CI=0.68‐1.08). However, when only trials of VSL#3 were considered there appeared to be a benefit (RR=0.74; 95% CI=0.63‐0.87). Probiotics appeared equivalent to 5‐ASAs in preventing UC relapse (RR=1.02; 95% CI=0.85‐1.23). There was no benefit of probiotics in inducing remission of active CD, in preventing relapse of quiescent CD, or in preventing relapse of CD after surgically induced remission. Conclusions VSL#3 may be effective in inducing remission in active UC. Probiotics may be as effective as 5‐ASAs in preventing relapse of quiescent UC. The efficacy of probiotics in CD remains uncertain, and more evidence from RCTs is required before their utility is known.

Mini AbstractPatients undergoing major surgery are at risk of life-threatening complications including systemic inflammatory response syndrome (SIRS) and sepsis. Early post-operative expression of TLR4 and TLR5 and their downstream signalling pathways in monocytes leads to over-expression of IL-6 and can predict SIRS in patients undergoing hepatopancreaticobiliary surgery. Running Title -Monocyte dysfunction in post-operative SIRS AbstractObjective To study innate immune pathways in hepatopancreaticobiliary (HPB) surgical patients to understand mechanisms leading to enhanced inflammatory responses and identifying biomarkers of adverse clinical consequences. Summary Background Data Patients undergoing major abdominal surgery are at risk of life-threatening systemic inflammatory response syndrome (SIRS) and sepsis. Early identification of at-risk patients would allow tailored post-operative care and improve survival. Methods Two separate cohorts of patients undergoing major HPB surgery were studied (combined n=69). Bloods were taken pre-operatively, on day 1 and day 2 post-operatively. Peripheral blood mononuclear cells and serum were separated and immune phenotype and function assessed ex vivo. Results Early innate immune dysfunction was evident in 12 patients who subsequently developed SIRS (post-operative day 6) compared to 27 who did not, when no clinical evidence of SIRS was apparent (pre-operatively or days 1 and 2). Serum interleukin (IL)-6 concentration and monocyte TLR/NF-DB/IL-6 functional pathways were significantly upregulated and overactive in patients who developed SIRS (p<0.0001). Interferon alpha-mediated STAT1 phosphorylation was higher pre-operatively in patients who developed SIRS. Increased TLR4 and TLR5 gene expression in whole blood was demonstrated in a separate validation cohort of 30 patients undergoing similar surgery. Expression of TLR4/5 on monocytes, particularly intermediate CD14 ++ CD16 + monocytes, on day 1 or 2 predicted SIRS with accuracy 0.89-1.0 (areas under receiver operator curves). Conclusions These data demonstrate the mechanism for IL-6 overproduction in patients who develop post-operative SIRS and identify markers that predict patients at risk of SIRS 5 days before onset of 30 patients undergoing similar surgery. Expression of TLR4/5 on monocytes, particularly intermediate CD14 ++ CD16 + monocytes, on day 1 or 2 predicted SIRS with accuracy 0.89-1.0 (areas under receiver operator curves).

Objectives:Patient-reported symptoms correlate poorly with mucosal inflammation. Clinical decision-making may, therefore, not be based on objective evidence of disease activity. We conducted a study to determine factors associated with clinical decision-making in a secondary care inflammatory bowel disease (IBD) population, using a cross-sectional design.Methods:Decisions to request investigations or escalate medical therapy were recorded from outpatient clinic encounters in a cohort of 276 patients with ulcerative colitis (UC) or Crohn’s disease (CD). Disease activity was assessed using clinical indices, self-reported flare or faecal calprotectin ≥ 250 µg/g. Demographic, disease-related and psychological factors were assessed using validated questionnaires. Logistic regression was performed to determine the association between clinical decision-making and symptoms, mucosal inflammation and psychological comorbidity.Results:Self-reported flare was associated with requesting investigations in CD [odds ratio (OR) 5.57; 95% confidence interval (CI) 1.84–17.0] and UC (OR 10.8; 95% CI 1.8–64.3), but mucosal inflammation was not (OR 1.62; 95% CI 0.49–5.39; and OR 0.21; 95% CI 0.21–1.05, respectively). Self-reported flare (OR 7.96; 95% CI 1.84–34.4), but not mucosal inflammation (OR 1.67; 95% CI 0.46–6.13) in CD, and clinical disease activity (OR 10.36; 95% CI 2.47–43.5) and mucosal inflammation (OR 4.26; 95% CI 1.28–14.2) in UC were associated with escalation of medical therapy. Almost 60% of patients referred for investigation had no evidence of mucosal inflammation.Conclusions:Apart from escalation of medical therapy in UC, clinical decision-making was not associated with mucosal inflammation in IBD. The use of point-of-care calprotectin testing may aid clinical decision-making, improve resource allocation and reduce costs in IBD.

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Background:Fatigue is a well-recognized symptom in patients with inflammatory bowel disease and irritable bowel syndrome (IBS), and has been associated with psychological comorbidity and impaired quality of life in both. However, features associated with fatigue in patients with microscopic colitis (MC) are less clear.Materials and methods:We conducted a cross-sectional survey of patients with a new diagnosis of MC including levels of anxiety, depression, somatization, quality of life, and IBS-type symptoms. Levels and impact of fatigue were assessed using the Inflammatory Bowel Disease Fatigue self-assessment scale. Mean scores were compared against various patient characteristics, and were also correlated with anxiety, depression, somatization, and quality-of-life scores.Results:In total, 129 patients with MC diagnosed between 2010 and 2015 returned completed postal questionnaires. Common histological subtypes were collagenous colitis (53.5%, n = 69) and lymphocytic colitis (38.8%, n = 50). Higher mean fatigue severity and impact scores were associated with the presence of irritable-bowel-syndrome-type symptoms, abnormal levels of anxiety and depression, and high levels of somatization (p < 0.0001 for all), but those reporting ongoing symptoms attributable to MC did not report significantly higher scores. There were significant positive correlations between total anxiety, depression, or somatization scores and fatigue severity and impact scores, and significant negative correlations with quality-of-life measures (p < 0.001 for all).Conclusions:Fatigue in MC appears to be associated with reporting IBS-type symptoms, psychological comorbidity and impaired quality of life. It may therefore represent an important target for treatment.

Background:Patients with microscopic colitis (MC) often present with abdominal pain and diarrhoea, and previous data suggest that there may be overlap between MC and irritable bowel syndrome (IBS). We evaluated the prevalence of IBS-type symptoms in patients with MC, and assess the impact of these symptoms on psychological health and quality of life.Methods:We conducted a cross-sectional survey of individuals with a histological diagnosis of MC, collecting demographic data, Rome III IBS-type symptoms, and mood, somatization, and quality of life data.Results:In total, 151 (31.6%) of 478 individuals with a new diagnosis of MC completed questionnaires, 52 (34.4%) of whom reported IBS-type symptoms. The commonest histological subtype was collagenous colitis (51.7%, n = 78), followed by lymphocytic colitis (39.1%, n = 59). Individuals with IBS-type symptoms had significantly higher levels of anxiety [Hospital Anxiety and Depression Scale (HADS) anxiety score 8.6 versus 5.1, p < 0.001], depression (HADS depression score 6.2 versus 3.6, p = 0.001), and somatoform-type behaviour (Patient Health Questionnaire 15 score 12.7 versus 8.0, p < 0.001) compared with individuals who did not. Those with IBS-type symptoms scored significantly worse across all domains of the 36-item Short Form questionnaire, except for physical functioning.Conclusions:More than one third of individuals with MC reported IBS-type symptoms, although whether this is due to ongoing inflammation is unclear. These individuals had higher levels of anxiety, depression, and somatization, and impaired quality of life. Identifying concomitant IBS in individuals with MC may have important implications for management decisions.

Background: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD). Evidence implicates disturbances of the gastrointestinal microbiota in their pathogenesis. We performed a systematic review and meta-analysis to examine the efficacy of probiotics in IBD. Methods: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (up to November 2016). Eligible randomised controlled trials (RCTs) recruited adults with UC or CD, and compared probiotics with 5-aminosalicylates (5-ASAs) or placebo. Dichotomous symptom data were pooled to obtain a relative risk (RR) of failure to achieve remission in active IBD, or RR of relapse of disease activity in quiescent IBD, with 95% confidence intervals (CIs). Results: The search identified 12,251 citations. Twenty-two RCTs were eligible. There was no benefit of probiotics over placebo in inducing remission in active UC (RR of failure to achieve remission = 0.86; 95% CI 0.68–1.08). Figure 1. Forest plot of randomised controlled trials reporting the efficacy of probiotics versus placebo in inducing remission in active UC, or in preventing relapse in quiescent UC. However, when only trials of VSL#3 were considered there appeared to be a benefit (RR =0.74; 95% CI 0.63–0.87). Probiotics appeared equivalent to 5-ASAs in preventing UC relapse (RR =1.02 (95% CI 0.85 to 1.23). Figure 2. Forest plot of randomised controlled trials reporting the efficacy of probiotics versus 5-aminosalicylates in Inducing remission in active UC, or in preventing relapse in quiescent UC. There was no benefit of probiotics in inducing remission of active CD, in preventing relapse of quiescent CD, or in preventing endoscopic or clinical relapse of CD after surgically induced remission. Figure 3. Forest plot of randomised controlled trials reporting the efficacy of probiotics versus placebo in inducing remission in active CD, or in preventing relapse in quiescent CD. Conclusions: VSL#3 appears to be effective in inducing remission in active UC, and probiotics may be as effective as 5-ASAs in preventing relapse of quiescent UC. However, the efficacy of probiotics in CD remains uncertain, and more evidence from RCTs is required before their utility is known.

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