Project description:The etiopathogenesis of Inflammatory bowel disease (IBD) is a result of a complex interaction between host immune response, the gut microbiome and environmental factors, such as diet. Although scientific advances, with the use of biological medications, have revolutionized IBD treatment, the challenge for maintaining clinical remission and delaying clinical relapse is still present. As exclusive enteral nutrition has become a well-established treatment for the induction of remission in pediatric Crohn's disease, the scientific interest regarding diet in IBD is now focused on the development of follow-on dietary strategies, which aim to suppress colonic inflammation and delay a disease flare. The objective of this review is to present an extensive overview of the dietary strategies, which have been used in the literature to maintain clinical remission in both Crohn's disease and Ulcerative colitis, and the evidence surrounding the association of dietary components with clinical relapse. We also aim to provide study-related recommendations to be encompassed in future research studies aiming to investigate the role of diet during remission periods in IBD.
Project description:BACKGROUND:Around 30% of patients with inflammatory bowel disease (IBD) are refractory to current IBD drugs or relapse over time. Novel treatments are called for, and low dose Naltrexone (LDN) may provide a safe, easily accessible alternative treatment option for these patients. We investigated the potential of LDN to induce clinical response in therapy refractory IBD patients, and investigated its direct effects on epithelial barrier function. METHODS:Patients not in remission and not responding to conventional therapy were offered to initiate LDN as a concomitant treatment. In total 47 IBD patients prescribed LDN were followed prospectively for 12 weeks. Where available, endoscopic remission data, serum and biopsies were collected. Further the effect of Naltrexone on wound healing (scratch assay), cytokine production and endoplasmic reticulum (ER) stress (GRP78 and CHOP western blot analysis, immunohistochemistry) were investigated in HCT116 and CACO2 intestinal epithelial cells, human IBD intestinal organoids and patient samples. RESULTS:Low dose Naltrexone induced clinical improvement in 74.5%, and remission in 25.5% of patients. Naltrexone improved wound healing and reduced ER stress induced by Tunicamycin, lipopolysaccharide or bacteria in epithelial barriers. Inflamed mucosa from IBD patients showed high ER stress levels, which was reduced in patients treated with LDN. Cytokine levels in neither epithelial cells nor serum from IBD patients were affected. CONCLUSIONS:Naltrexone directly improves epithelial barrier function by improving wound healing and reducing mucosal ER stress levels. Low dose Naltrexone treatment is effective and safe, and could be considered for the treatment of therapy refractory IBD patients.
Project description:Diet is intimately linked to the gastrointestinal (GI) tract and has potent effects on intestinal immune homeostasis. Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the GI tract. The therapeutic implications of diet in patients with IBD have received significant attention in recent years. In this review, we provide a contemporary and comprehensive overview of dietary exposures and interventions in IBD. Epidemiological studies suggest that ultra-processed foods, food additives, and emulsifiers are associated with a higher incidence of IBD. Exclusion and elimination diets are associated with improved symptoms in patients with IBD, but no effects on objective markers of inflammation. Specific dietary interventions (e.g., Mediterranean, specific carbohydrate, high fiber, ketogenic, anti-inflammatory diets) have been shown to reduce symptoms, improve inflammatory biomarkers, and quality of life metrics to varying degrees, but these studies are limited by study design, underpowering, heterogeneity, and confounding. To date, there is no robust evidence that any dietary intervention alone may replace standard therapies in patients with IBD. However, diet may play an adjunct role to induce or maintain clinical remission with standard IBD therapies. The results of novel dietary trials in IBD such as personalized fiber, intermittent fasting, and time-restricted diets are eagerly awaited.
Project description:BACKGROUND AND AIMS:Vedolizumab is an anti-?4?7 biologic approved for ulcerative colitis [UC] and Crohn's disease [CD]. We aimed to examine the association of maintenance vedolizumab concentrations with remission. METHODS:We performed a cross-sectional multi-centre study of inflammatory bowel disease [IBD] patients on maintenance vedolizumab. A homogeneous mobility shift assay [HMSA] was used to determine trough serum concentrations of vedolizumab and anti-drug antibodies [ATVs]. The primary outcome was corticosteroid-free clinical and biochemical remission defined as a composite of clinical remission, normalized C-reactive protein [CRP] and no corticosteroid use in 4 weeks. Secondary outcomes included corticosteroid-free endoscopic and deep remission. Vedolizumab concentrations were compared between patients in remission and with active disease. Logistic regression, adjusting for confounders, assessed the association between concentrations and remission. RESULTS:In total, 258 IBD patients were included [55% CD and 45% UC]. Patients in clinical and biochemical remission had significantly higher vedolizumab concentrations [12.7 µg/mL vs 10.1 µg/mL, p = 0.002]. Concentrations were also higher among patients in endoscopic and deep remission [14.2 µg/mL vs 8.5 µg/mL, p = 0.003 and 14.8 µg/mL vs 10.1 µg/mL, p = 0.01, respectively]. After controlling for potential confounders, IBD patients with vedolizumab concentrations >11.5 µg/mL were nearly 2.4 times more likely to be in corticosteroid-free clinical and biochemical remission. Only 1.6% of patients had ATVs. CONCLUSIONS:In a large real-world cohort of vedolizumab maintenance concentrations, IBD patients with remission defined by objective measures [CRP and endoscopy] had significantly higher trough vedolizumab concentrations and immunogenicity was uncommon.
Project description:Introduction: Adalimumab is effective in inducing and maintaining remission in children with inflammatory bowel diseases (IBD). Therapeutic drug monitoring is an important strategy to maximize the response rates, but data on the association of serum adalimumab levels are lacking. This study aimed to assess the association of adalimumab concentrations at the end of induction and early during maintenance for long-term response. Materials and Methods: Serum samples for adalimumab level measurement were collected during routine visits between adalimumab administrations and therefore not necessarily at trough, both during the induction (week 4 ± 4) and maintenance phases (week 22 ± 4, 52 ± 4, and 82 ± 4). Adalimumab and anti-adalimumab antibodies were measured retrospectively using enzyme-linked immunosorbent assays (ELISA). Disease activity was determined by Pediatric Crohn's Disease Activity Index or Pediatric Ulcerative Colitis Activity Index. Results: Thirty-two children (median age 14.9 years) were enrolled. Sixteen, 15, 14, and 12 patients were in remission at weeks 4, 22, 52, and 82, respectively. Median adalimumab concentration was higher at all time points in patients achieving sustained clinical remission. Adalimumab levels correlated with clinical and biochemical variables. Adalimumab concentration above 13.85 and 7.54 μg/ml at weeks 4 and 22 was associated with remission at weeks 52 and 82. Conclusions: Adalimumab non-trough levels are associated with long-term response in pediatric patients with IBD.
Project description:Patients with inflammatory bowel disease have adopted medical jargon terms of "flare" and "remission," but what they mean by these terms is ill-defined and may have implications for nurse-patient communication and treatment expectancy. The aim of this study was to elicit patients' understanding of "flare" and "remission." Individuals with self-reported inflammatory bowel disease were recruited through social media. A web-based survey, with closed and open-ended questions, was administered. Conventional content analysis was used to evaluate respondents' perceptions of jargon terms. A word cloud was generated to augment analysis by visualization of word use frequency. A majority of the 34 respondents had a symptom-focused understanding and described these terms as alternating states. Various symptoms were understood to signify "flare," which was largely attributed to lifestyle factors. Corroborated by the word cloud, there was rare mention of inflammation or tissue damage. This study demonstrates that an understanding of "flare" and "remission" by patients with inflammatory bowel disease is largely symptom-based. The role of inflammation, medication failure, and targets of inflammatory bowel disease treatment beyond symptom control are not currently well known to patients with inflammatory bowel disease. To create a shared understanding of symptoms and treatment goals between the patient and the nurse, patient education on emerging expectations of inflammatory bowel disease care should be prioritized.