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Background: Riboflavin is a redox-active vitamin that plays a pivotal role in human energy metabolism. Riboflavin may have beneficial health effects by increasing extracellular antioxidant capacity, thereby alleviating oxidative stress. Reduced levels of free thiols in blood reflect systemic oxidative stress, since they are readily oxidized by reactive species. In this study, we aimed to study the potential of riboflavin supplementation to improve the systemic redox status in healthy volunteers.Methods: This study was a post-hoc analysis of the RIBOGUT study, a randomized, double-blind, placebo-controlled human intervention trial that investigated the effect of riboflavin supplements on the gut microbiota composition of healthy individuals. Serum free thiols were quantified before and after intervention and adjusted to serum albumin levels. Changes in albumin-adjusted free thiols were analyzed, as well as potential associations with routine laboratory parameters and fecal bacterial quantification by fluorescence in-situ hybridization (FISH).Results: Participants were randomized to either placebo (n=34), riboflavin 50 mg daily (n=32), or riboflavin 100 mg daily (n=33). At baseline, no significant differences in albumin-adjusted serum free thiols were observed. After intervention with either placebo or riboflavin, albumin-adjusted serum free thiols did not significantly change (P>0.05), however, observed changes were inversely associated with changes in C-reactive protein (CRP) levels (r= -0.22, PConclusion: Riboflavin did not change the systemic redox status in healthy individuals as reflected by serum free thiols, but observed changes in albumin-adjusted free thiol levels were negatively associated with changes in CRP levels. Strikingly, albumin-adjusted free thiols were independently associated with relative abundances of fecal F. prausnitzii, which may suggest a potential host redox-microbiota interaction.

Background: Increased collagen remodelling is a key pathophysiological component underlying intestinal stricture and fistula development in Crohn's disease (CD).Aims: To investigate associations between serological biomarkers of collagen turnover and disease behaviour according to the Montreal classification in patients with CD.Methods: Serological biomarkers of type III/IV collagen formation (PRO-C3, PRO-C4) and matrix metalloproteinase (MMP) or granzyme-B (GrzB)-mediated type I, III, IV and VI collagen degradation (C1M, C3M, C4M, C4G, C6Ma3) were measured using neo-epitope protein fingerprint assays in 101 patients with CD (Montreal B1: n = 37; B2: n = 27; B3: n = 37) and 96 controls. Patients were followed up until their last outpatient visit to monitor stricturing/penetrating disease progression and recurrence and the occurrence of surgical interventions.Results: C1M, C3M and C4M were significantly reduced in patients with stricturing disease (Montreal B2) and accurately differentiated them from patients with either non-stricturing, non-penetrating (B1) or penetrating (B3) disease (all p Conclusions: Elevated degradation of type I, III and IV collagen and excessive (relative) formation of type IV collagen strongly associates with stricturing CD. Type I and IV collagen fragments show predictive potential for the risk of penetrating disease progression. These biomarkers may become valuable tools for detection and prediction of stricturing and penetrating CD.

Aim: Creation of a diverting stoma in patients with Crohn's disease (CD) can counteract luminal inflammation. The clinical utility of a diverting stoma with the prospect of restoration of gastrointestinal continuity warrants further investigation. The aim of this work was to evaluate the long-term effects of creation of a diverting stoma on the disease course in patients with luminal colonic CD. Method: In this retrospective, multicentre cohort study we investigated the disease course of patients who received a diverting stoma in the biological era. Clinical characteristics, medication use and surgical course were assessed at the time of creation of the diverting stoma and during follow-up. The primary outcome was the rate of successful and lasting reestablishment of gastrointestinal continuity. Results: Thirty six patients with refractory luminal CD from four institutions underwent creation of a diverting stoma. Of the overall cohort, 20 (56%) patients had their gastrointestinal continuity reestablished after initial stoma creation and 14 (39%) who had their stoma reversed remained stoma-free during a median of 3.3 years follow-up (interquartile range 2.1–6.1 years). Absence of stoma reversal was associated with the presence of proctitis (p = 0.02). Colorectal resection after creation of a diverting stoma was performed in 28 (78%) patients, with 7 (19%) having a less extensive resection and 6 (17%) having a more extensive resection compared with the surgical plan before stoma creation. Conclusion: A diverting stoma could potentially be an alternative to immediate definitive stoma placement in specific populations consisting of patients with luminal colonic CD, especially in the absence of proctitis.

Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by intestinal inflammation. Increased intestinal levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) are associated with disease activity and severity. Anti-TNF-α therapy is administered systemically and efficacious in the treatment of IBD. However, systemic exposure is associated with adverse events that may impede therapeutic treatment. Clinical studies show that the efficacy correlates with immunological effects localized in the gastrointestinal tract (GIT) as opposed to systemic effects. These data suggest that site-specific TNF-α inhibition in IBD may be efficacious with fewer expected side effects related to systemic exposure. We therefore reviewed the available literature that investigated the efficacy or feasibility of local TNF-α inhibition in IBD. A literature search was performed on PubMed with given search terms and strategy. Of 8739 hits, 48 citations were included in this review. These studies ranged from animal studies to randomized placebo-controlled clinical trials. In these studies, local anti-TNF-α therapy was achieved with antibodies, antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and genetically modified organisms. This narrative review summarizes and discusses these approaches in view of the clinical relevance of local TNF-α inhibition in IBD.

Research shows that topically active infliximab therapy may be efficacious in the treatment of inflammatory bowel disease (IBD) with expected fewer side effects related to systemic exposure. Oral administration of infliximab with site-specific delivery could enable such therapy. In the present study, infliximab was incorporated in a sugar glass matrix (IFX-I) for additional stability and compounding flexibility after which IFX-I was compounded to ileo-colonic-targeted tablets containing 5 mg infliximab (ColoPulse-IFX). Potential critical steps in the production process that may decrease the formulation stability were identified and investigated. Furthermore, the long-term stability of IFX-I (6 months) and ColoPulse-IFX (12 months) stored either at room temperature (25 degrees C +/-+/- 2 degrees C/60% RH +/- 5% RH) or refrigerated (5 degrees C +/- 3 degrees C) was investigated according to ICH guidelines. Size-exclusion chromatography, fluorescence spectroscopy, and ELISA analyses were used to investigate the infliximab stability, content, tertiary protein structure, and potency at t0, t3, t6, t9, and t12 months. The coating performance of ColoPulse-IFX was investigated in a gastrointestinal simulation system at t0 and t12 months. All the analyses showed that IFX-I and ColoPulse-IFX were stable, potent, and that the coating performance was maintained during the entire storage period at both storage conditions. Thus, IFX-I is a stable drypowder formulation and ColoPulse-IFX is a promising oral dosage form for the topical treatment of ileocolonic IBD. This formulation strategy may serve as a new platform for the development of oral peptide or protein formulations that are targeted to the ileo-colonic region in IBD.