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BACKGROUND: There are a limited number of treatment options for people with corticosteroid‐refractory ulcerative colitis. Animal models of inflammatory bowel disease and uncontrolled studies in humans suggest that tacrolimus may be an effective treatment for ulcerative colitis. OBJECTIVES: To evaluate the efficacy and safety of tacrolimus for induction of remission in people with corticosteroid‐refractory ulcerative colitis. SEARCH METHODS: We searched the Cochrane Gut group specialised register, CENTRAL, MEDLINE (PubMed), Embase, Clinicaltrials.gov and WHO ICTRP from inception to October 2021 to identify relevant randomised controlled trials (RCT). SELECTION CRITERIA: Two review authors independently selected potentially relevant studies to determine eligibility based on the prespecified criteria. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and analysed them using Review Manager Web. The primary outcomes were induction of remission and clinical improvement, as defined by the studies and expressed as a percentage of the participants randomised (intention‐to‐treat analysis). MAIN RESULTS: This review included five RCTs with 347 participants who had active ulcerative colitis or ulcerative proctitis. The duration of intervention varied between two weeks and eight weeks. Tacrolimus versus placebo Tacrolimus (oral and rectal) may be superior in achieving clinical remission compared to placebo (oral and rectal) (14/87 participants with tacrolimus versus 1/61 participants with placebo; risk ratio (RR) 3.76, 95% confidence interval (CI) 1.03 to 13.73; 3 studies). These results are of low certainty due to imprecision and risk of bias. Tacrolimus (oral and rectal) may be superior for clinical improvement compared to placebo (oral and rectal) (45/87 participants with tacrolimus versus 7/61 participants with placebo; RR 4.47, 95% CI 2.15 to 9.29; 3 studies). These results are of low certainty due to imprecision and risk of bias. The evidence is very uncertain about the effects of tacrolimus (oral and rectal) on serious adverse events compared to placebo (oral and rectal) (2/87 participants with tacrolimus versus 0/61 participants with placebo; RR 2.44, 95% CI 0.12 to 48.77; 3 studies). These results are of very low certainty due to high imprecision and risk of bias. Tacrolimus versus ciclosporin One study compared oral tacrolimus to intravenous ciclosporin, with an intervention lasting two weeks and 113 randomised participants. The evidence is very uncertain about the effect of tacrolimus on achievement of clinical remission compared to ciclosporin (15/33 participants with tacrolimus versus 24/80 participants with ciclosporin; RR 1.52, 95% CI 0.92 to 2.50). The results are of very low certainty due to risk of bias and high imprecision. The evidence is very uncertain about the effect of tacrolimus on clinical improvement compared to intravenous ciclosporin (23/33 participants with tacrolimus versus 62/80 participants with ciclosporin; RR 0.90, 95% CI 0.70 to 1.16). The results are of very low certainty due to risk of bias and imprecision. Tacrolimus versus beclometasone One study compared tacrolimus suppositories with beclometasone suppositories in an intervention lasting four weeks with 88 randomised participants. There may be little to no difference in achievement of clinical remission (16/44 participants with tacrolimus versus 15/44 participants with beclometasone; RR 1.07, 95% CI 0.60 to 1.88). The results are of low certainty due to high imprecision. There may be little to no difference in clinical improvement when comparing tacrolimus suppositories to beclometasone suppositories (22/44 participants with tacrolimus versus 22/44 with beclometasone; RR 1.00, 95% CI 0.66 to 1.52). The results are of low certainty due to high imprecision. There may be little to no difference in serious adverse events when comparing tacrolimus suppositories to beclometasone suppositories (1/44 participants with tacrolimus versus 0/44 with beclometasone; RR 3.00, 95% CI 0.13 to 71.70). These results are of low certainty due to high imprecision. There may be little to no difference in total adverse events when comparing tacrolimus suppositories to beclometasone suppositories (21/44 participants with tacrolimus versus 14/44 participants with beclometasone; RR 1.50, 95% CI 0.88 to 2.55). These results are of low certainty due to high imprecision. No secondary outcomes were reported for people requiring rescue medication or to undergo surgery. AUTHORS' CONCLUSIONS: There is low‐certainty evidence that tacrolimus may be superior to placebo for achievement of clinical remission and clinical improvement in corticosteroid‐refractory colitis or corticosteroid‐refractory proctitis. The evidence is very uncertain about the effect of tacrolimus compared to ciclosporin for achievement of clinical remission or clinical improvement. There may be no difference between tacrolimus and beclometasone for inducing clinical remission or clinical improvement. The cohorts studied to date were small, with missing data sets, offered short follow‐up and the clinical endpoints used were not in line with those suggested by regulatory bodies. Therefore, no clinical practice conclusions can be made. This review highlights the need for further research that targets the relevant clinical questions, uses appropriate trial methodology and reports key findings in a systematic manner that facilitates future integration of findings with current evidence to better inform clinicians and patients. Future studies need to be adequately powered and of pertinent duration so as to capture the efficacy and effectiveness of tacrolimus in the medium to long term. Well‐structured efficacy studies need to be followed up by long‐term phase 4 extensions to provide key outputs and inform in a real‐world setting.

BACKGROUND: Functional constipation is defined as chronic constipation with no identifiable underlying cause. It is a significant cause of morbidity in children, accounting for up to 25% of visits to paediatric gastroenterologists. Probiotic preparations may sufficiently alter the gut microbiome and promote normal gut physiology in a way that helps relieve functional constipation. Several studies have sought to address this hypothesis, as well as the role of probiotics in other functional gut disorders. Therefore, it is important to have a focused review to assess the evidence to date. OBJECTIVES: To evaluate the efficacy and safety of probiotics for the management of chronic constipation without a physical explanation in children. SEARCH METHODS: On 28 June 2021, we searched CENTRAL, MEDLINE, Embase, CINAHL, AMED, WHO ICTR, and ClinicalTrials.gov, with no language, date, publication status, or document type limitations. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that assessed probiotic preparations (including synbiotics) compared to placebo, no treatment or any other interventional preparation in people aged between 0 and 18 years old with a diagnosis of functional constipation according to consensus criteria (such as Rome IV). DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 14 studies (1127 randomised participants): 12 studies assessed probiotics in the treatment of functional constipation, whilst two studies investigated synbiotic preparations. Three studies compared probiotics to placebo in relation to the frequency of defecation at study end, but we did not pool them as there was very significant unexplained heterogeneity. Four studies compared probiotics to placebo in relation to treatment success. There may be no difference in global improvement/treatment success (RR 1.29, 95% CI 0.73 to 2.26; 313 participants; low‐certainty evidence). Five studies compared probiotics to placebo in relation to withdrawals due to adverse events, with the pooled effect suggesting there may be no difference (RR 0.64, 95% CI 0.21 to 1.95; 357 participants; low‐certainty evidence). The pooled estimate from three studies that compared probiotics plus an osmotic laxative to osmotic laxative alone found there may be no difference in frequency of defecation (MD ‐0.01, 95% CI ‐0.57 to 0.56; 268 participants; low‐certainty evidence). Two studies compared probiotics plus an osmotic laxative to osmotic laxative alone in relation to global improvement/treatment success, and found there may be no difference between the treatments (RR 0.95, 95% CI 0.79 to 1.15; 139 participants; low‐certainty evidence). Three studies compared probiotics plus osmotic laxative to osmotic laxative alone in relation to withdrawals due to adverse events, but it is unclear if there is a difference between them (RR 2.86, 95% CI 0.12 to 68.35; 268 participants; very low‐certainty evidence). Two studies compared probiotics versus magnesium oxide. It is unclear if there is a difference in frequency of defecation (MD 0.28, 95% CI ‐0.58 to 1.14; 36 participants), treatment success (RR 1.08, 95% CI 0.74 to 1.57; 36 participants) or withdrawals due to adverse events (RR 0.50, 95% CI 0.05 to 5.04; 77 participants). The certainty of the evidence is very low for these outcomes. One study assessed the role of a synbiotic preparation in comparison to placebo. There may be higher treatment success in favour of synbiotics compared to placebo (RR 2.32, 95% CI 1.54 to 3.47; 155 participants; low‐certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group. One study assessed a synbiotic plus paraffin compared to paraffin alone. It is uncertain if there is a difference in frequency of defecation (MD 0.74, 95% CI ‐0.96, 2.44; 66 participants; very low‐certainty evidence), or treatment success (RR 0.91, 95% CI 0.71 to 1.17; 66 participants; very low‐certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group. One study compared a synbiotic preparation to paraffin. It is uncertain if there is a difference in frequency of defecation (MD ‐1.53, 95% CI ‐3.00, ‐0.06; 60 participants; very low‐certainty evidence) or in treatment success (RR 0.86, 95% CI 0.65, 1.13; 60 participants; very low‐certainty evidence). The study reported that there were no withdrawals due to adverse effects in either group. All secondary outcomes were either not reported or reported in a way that did not allow for analysis. AUTHORS' CONCLUSIONS: There is insufficient evidence to conclude whether probiotics are efficacious in successfully treating chronic constipation without a physical explanation in children or changing the frequency of defecation, or whether there is a difference in withdrawals due to adverse events when compared with placebo. There is limited evidence from one study to suggest a synbiotic preparation may be more likely than placebo to lead to treatment success, with no difference in withdrawals due to adverse events. There is insufficient evidence to draw efficacy or safety conclusions about the use of probiotics in combination with or in comparison to any of the other interventions reported. The majority of the studies that presented data on serious adverse events reported that no events occurred. Two studies did not report this outcome. Future studies are needed to confirm efficacy, but the research community requires guidance on the best context for probiotics in such studies, considering where they should be best considered in a potential treatment hierarchy and should align with core outcome sets to support future interpretation of findings.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows:\ud \ud To assess the efficacy and safety of prebiotics for the induction of remission in people with active ulcerative colitis.

Purpose Although genetic predisposition and exposure to dietary gluten are considered necessary triggers for the development of coeliac disease, alterations in the gut microbial composition may also contribute towards the pathogenesis of coeliac disease. This review aims to provide an overview of the available data on the potential mechanisms through which the gut microbiota plays a role in the causation of coeliac disease and to discuss the potential therapeutic strategies that could diminish the consequences of microbial dysbiosis. Method A search of the literature was performed using the PubMed, Embase, and JSTOR databases; relevant articles were included. Results Recent studies in patients with coeliac disease have reported an increase in the relative amounts of gram negative bacterial genera such as Bacteroides, Prevotella, and Escherichia, and reduced amounts of protective anti-inflammatory bacteria such as Bifidobacteria and Lactobacilli. Dysbiotic microbiota may lead to a dysregulated immune response that may contribute to the pathogenesis of coeliac disease. In infancy, antibiotic use and certain infant feeding practices may lead to alterations in the developing gut microbiota to influence the immune maturation process and predispose to coeliac disease. Conclusion The induction of the intestinal immune system and gluten intolerance may be influenced by the relative abundance of certain microbiota. Factors such as infant feeding practices, diet, antibiotics, and infections, may be involved in the development of coeliac disease due to their influence on gut microbial composition. The efficacy of potential modulators of the gut microbiota such as probiotics, prebiotics, and fecal microbial transplant as adjunctive treatments to gluten-free diet in coeliac disease is unproven and requires further investigation.Other Information Published in: European Journal of Nutrition License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s00394-020-02324-y

Objectives\ud This is a protocol for a Cochrane Review (intervention). The objectives are as follows:\ud \ud To assess the efficacy and safety of interventions for managing abdominal pain in ulcerative colitis.