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Summary: Background: Patients with IBD are at risk of excess corticosteroids. Aims: To assess steroid excess in a large IBD cohort and test associations with quality improvement and prescribing. Methods: Steroid exposure was recorded for outpatients attending 19 centres and associated factors analysed. Measures taken to avoid excess were assessed. Results: Of 2385 patients, 28% received steroids in the preceding 12 months. 14.8% had steroid excess or dependency. Steroid use was significantly lower at 'intervention centres' which participated in a quality improvement programme (exposure: 23.8% vs 31.0%, P < .001; excess 11.5% vs 17.1%, P < .001). At intervention centres, steroid use fell from 2015 to 2017 (steroid exposure 30.0%‐23.8%, P = .003; steroid excess 13.8%‐11.5%, P = .17). Steroid excess was judged avoidable in 50.7%. Factors independently associated with reduced steroid excess in Crohn's disease included maintenance with anti‐TNF agents (OR 0.61 [95% CI 0.24‐0.95]), treatment in a centre with a multi‐disciplinary team (OR 0.54 [95% CI 0.20‐0.86]) and treatment at an intervention centre (OR 0.72 [95% CI 0.46‐0.97]). Treatment with 5‐ASA in CD was associated with higher rates of steroid excess (OR 1.72 [95% CI 1.24‐2.09]). In ulcerative colitis (UC), thiopurine monotherapy was associated with steroid excess (OR 1.97 [95% CI 1.19‐3.01]) and treatment at an intervention centre with less steroid excess (OR 0.72 [95% CI 0.45‐0.95]). Conclusions: This study validates steroid assessment as a meaningful quality measure and provides a benchmark for this performance indicator in a large cohort. A programme of quality improvement was associated with lower steroid use. [ABSTRACT FROM AUTHOR]

Background: Abnormal handling of E. coli by lamina propria (LP) macrophages may contribute to Crohn's disease (CD) pathogenesis. We aimed to determine LP macrophage phenotypes in CD, ulcerative colitis (UC) and healthy controls (HC), and in CD, to compare macrophage phenotypes according to E. coli carriage. Methods: Mucosal biopsies were taken from 35 patients with CD, 9 with UC and 18 HCs. Laser capture microdissection was used to isolate E. coli-laden and unladen LP macrophages from ileal or colonic biopsies. From these macrophages, mRNA was extracted and cytokine and activation marker expression measured using RT-qPCR. Results: E. coli-laden LP macrophages were identified commonly in mucosal biopsies from CD patients (25/35, 71 %), rarely in UC (1/9, 11 %) and not at all in healthy controls (0/18). LP macrophage cytokine mRNA expression was greater in CD and UC than healthy controls. In CD, E. coli-laden macrophages expressed high IL-10 & CD163 and lower TNFα, IL-23 & iNOS irrespective of macroscopic inflammation. In inflamed tissue, E. coli-unladen macrophages expressed high TNFα, IL-23 & iNOS and lower IL-10 & CD163. In uninflamed tissue, unladen macrophages had low cytokine mRNA expression, closer to that of healthy controls. Conclusion: In CD, intra-macrophage E. coli are commonly found and LP macrophages express characteristic cytokine mRNA profiles according to E. coli carriage. Persistence of E. coli within LP macrophages may provide a stimulus for chronic inflammation. [ABSTRACT FROM AUTHOR]

The chronic intestinal inflammation that characterises Crohn's disease and ulcerative colitis arises from a complex interplay between host genotype, the immune system, and the intestinal microbiota. In addition, environmental factors such as smoking impact on disease onset and progression. Individuals who smoke are more likely to develop Crohn's disease, and smoking is associated with recurrence after surgery and a poor response to medical therapy. Conversely, smoking appears protective against ulcerative colitis and smokers are less likely to require colectomy. The mechanism by which smoking exerts its impact on disease and the rational for the dichotomous effect in patients with Crohn's disease and ulcerative colitis is not clear. Recent evidence suggests that smoking induces alterations to both the innate and acquired immune system. In addition, smoking is associated with a distinct alteration in the intestinal microbiota both in patients with active Crohn's disease and healthy subjects. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota is thought to play a key role in the development of the inflammatory bowel diseases Crohn's disease (CD) and ulcerative colitis (UC). Shifts in the composition of resident bacteria have been postulated to drive the chronic inflammation seen in both diseases (the "dysbiosis" hypothesis). We therefore specifically sought to compare the mucosa-associated microbiota from both inflamed and non-inflamed sites of the colon in CD and UC patients to that from non-IBD controls and to detect disease-specific profiles. Results: Paired mucosal biopsies of inflamed and non-inflamed intestinal tissue from 6 CD (n = 12) and 6 UC (n = 12) patients were compared to biopsies from 5 healthy controls (n = 5) by in-depth sequencing of over 10,000 near full-length bacterial 16S rRNA genes. The results indicate that mucosal microbial diversity is reduced in IBD, particularly in CD, and that the species composition is disturbed. Firmicutes were reduced in IBD samples and there were concurrent increases in Bacteroidetes, and in CD only, Enterobacteriaceae. There were also significant differences in microbial community structure between inflamed and non-inflamed mucosal sites. However, these differences varied greatly between individuals, meaning there was no obvious bacterial signature that was positively associated with the inflamed gut. Conclusions: These results may support the hypothesis that the overall dysbiosis observed in inflammatory bowel disease patients relative to non-IBD controls might to some extent be a result of the disturbed gut environment rather than the direct cause of disease. Nonetheless, the observed shifts in microbiota composition may be important factors in disease maintenance and severity. [ABSTRACT FROM AUTHOR]