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).