Background: Vitamin D (vitD) supplementation may prolong remission in Crohn's disease (CD); however, the clinical efficacy and mechanisms are unclear.Aim: To determine changes in intestinal permeability (IP), antimicrobial peptide (AMP) concentrations and disease markers in CD, in response to vitD supplementation.Methods: In a double‐blind randomised placebo‐controlled study, we assigned 27 CD patients in remission to 2000 IU/day vitD or placebo for 3 mos. We determined IP, plasma cathelicidin (LL‐37 in ng/mL), human‐beta‐defensin‐2 (hBD2 in pg/mL), disease activity (Crohn's Disease Activity Index (CDAI)), C‐reactive protein (CRP in mg/L), fecal calprotectin (µg/g), Quality of Life (QoL) and serum 25‐hydroxyvitamin D (25(OH)D in nmol/L) at 0 and 3 mos.Results: At 3 mos., 25(OH)D concentrations were significantly higher in those whom were treated (p < 0.001). Intra‐group analysis showed increased LL‐37 concentrations (p = 0.050) and maintenance of IP measures in the treated group. In contrast, in the placebo group, the small bowel (p = 0.018) and gastro‐duodenal permeability (p = 0.030) increased from baseline. At 3 mos., patients with 25(OH)D ≥ 75 nmol/L had significantly lower CRP (p = 0.019), higher QoL (p = 0.037), higher LL‐37 concentrations (p < 0.001) and non‐significantly lower CDAI scores (p = 0.082), compared to those with levels <75 nmol/L.Conclusion: Short‐term treatment with 2000 IU/day vitD significantly increased 25(OH)D levels in CD patients in remission and it was associated with increased LL‐37 concentrations and maintenance of IP. Achieving 25(OH)D ≥ 75 nmol/l was accompanied by higher circulating LL‐37, higher QoL scores and reduced CRP. Registered at ClinicalTrials.gov (NCT01792388).

The gram-negative bacterium Helicobacter pylori (H. pylori) causes chronic gastritis, gastric and duodenal ulcers, gastric cancer and mucosa-associated lymphoid tissue lymphoma. Treatment is recommended in all symptomatic patients. The current treatment options for H. pylori infection are outlined in this review in light of the recent challenges in eradication success, largely due to the rapid emergence of antibiotic resistant strains of H. pylori. Antibiotic resistance is a constantly evolving process and numerous studies have shown that the prevalence of H. pylori antibiotic resistance varies significantly from country to country, and even between regions within the same country. In addition, recent data has shown that previous antibiotic use is associated with harbouring antibiotic resistant H. pylori. Local surveillance of antibiotic resistance is warranted to guide clinicians in their choice of therapy. Antimicrobial resistance is assessed by H. pylori culture and antimicrobial susceptibility testing. Recently developed molecular tests offer an attractive alternative to culture and allow for the rapid molecular genetic identification of H. pylori and resistance-associated mutations directly from biopsy samples or bacterial culture material. Accumulating evidence indicates that surveillance of antimicrobial resistance by susceptibility testing is feasible and necessary to inform clinicians in their choice of therapy for management of H. pylori infection.

Mucosal healing is increasingly recognised as an important treatment goal in Crohn's disease (CD). Data from colonic disease shows improved long-term outcomes in patients achieving complete mucosal healing. Little is currently known of this with regard to ileitis which is increasingly diagnosed using capsule endoscopy (SBCE). This is the first study to prospectively assess mucosal healing and deep remission rates following 52 weeks of therapy in a cohort of symptomatic small bowel CD patients commencing immunomodulator or biologic therapy. Baseline demographics, quality of life questionnaires and Harvey Bradshaw Index were collected along with C-reactive protein & calprotectin. Capsule endoscopy Crohn's disease activity (CECDAI) index was used to assess ileitis severity. All parameters were reassessed at week 52. Results at baseline & week 52 were compared using univariate analysis, p < 0.05 considered significant. In total, 108 capsule procedures were performed on 43 patients. Based on the CECDAI, 39 (90%) demonstrated active small bowel CD at baseline with 28 (65%) undergoing 52 week assessment. In total, 12 (42%) participants achieved complete mucosal healing and deep remission by 52 week assessment (p<0.0001 95% CI -0.62 to -0.22). Despite overall impressive mucosal healing rates, patients with strictures were less likely to demonstrate a decrease in CECDAI and were more likely to have symptoms. In patients with active small bowel CD symptomatic and biochemical response to treatment appears to be mirrored by endoscopic remission in 42% of individuals. Strictures identified prior to therapy appear to be a poor indicator for success of treatment.

Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition causing inflammation of gastrointestinal and systemic cells, with an increasing prevalence worldwide. Many factors are known to trigger and maintain inflammation in IBD including the innate and adaptive immune systems, genetics, the gastrointestinal microbiome and several environmental factors. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. The initial focus of these agents was directed against the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) leading to dramatic changes in the disease course for a proportion of patients with IBD. However, more recently, it has been shown that a significant proportion of patients do not respond to anti-TNF-α directed therapies, leading a shift to other inflammatory pathways and targets, including those of both the innate and adaptive immune systems, and targets linking both systems including anti-leukocyte trafficking agents-integrins and adhesion molecules. This review briefly describes the molecular basis of immune based gastrointestinal inflammation in IBD, and then describes how several current and future biologic agents work to manipulate these pathways, and their clinical success to date.