Increasing KYNA/T is closely associated with endoscopic inflammation and predictive of disease outcomes in patients with UC. These findings identify this novel metabolic association and further support the role of the KP in regulating mucosal inflammation in UC. 10.1093/ibd/izy103_video1izy103.video15788135676001.

Type 1 diabetes (T1D) and celiac disease (CD) are autoimmune diseases with clinical and pathogenic overlap. The mean prevalence of CD in patients with T1D is about 8%. Classic intestinal symptoms of CD may not be present in T1D leading to the recommendation for active case finding in this higher risk group. Screening is done with sensitive and specific serologies including tissue transglutaminase (tTG) IgA and deaminated gliadin peptide (DGP) IgA and IgG. Positive serologies are confirmed by the presence of villous atrophy and increased intraepithelial lymphocytes on duodenal biopsy. A strict gluten free diet is recommended, although this can pose challenges for T1D patients who already have dietary restrictions. In aggregate, it appears as if the gluten free diet may help T1D management. T1D and CD have overlapping genetic and environmental risk factors. Among these, non-HLA genetic factors and the gut microbiome are among recent developments that will be discussed in this review.

Background While the incidence of inflammatory bowel disease (IBD) among African-Americans (AAs) is increasing, there is limited understanding of phenotypic differences and outcomes by race. Aim To describe disease characteristics of AA patients compared to Caucasian (Ca) patients in a tertiary care population. Methods We performed a cross-sectional review of the IBD registry at the University of Chicago from January 2008 to January 2013. Data regarding race, phenotype, disease onset, disease duration, medical therapy, and surgical treatment were abstracted from the database, then compared via Pearson’s chi-square analysis, Kruskal–Wallis analysis, and logistic regression with a significance level of p < 0.05. Results A total of 1,235 patients with Crohn’s disease (CD) and 541 patients with ulcerative colitis (UC) included 108 AA CD patients and 28 AA UC patients. AA CD patients had an increased rate of IBD-related arthralgias (36.5 vs. 23.9 %, p < 0.01) and surgery (p < 0.01), less ileal involvement (57.8 vs. 71.0 %, p < 0.01), and no differences for other extraintestinal manifestations or disease locations compared to Ca CD patients. AA UC patients were older at diagnosis, had an increased rate of arthralgias (28.6 vs. 14.6 %, p = 0.047) and ankylosing spondylitis/sacroiliitis (7.1 vs. 1.6 %, p = 0.035), with no differences for disease extent or rate of IBD-related surgeries compared to Ca UC patients. There were no differences in medication usage by race for CD and UC patients. Conclusion We identified significant differences in disease characteristics and extraintestinal manifestations between AA and Ca IBD patients in a large tertiary care population. These results have implications for future genotype-phenotype studies.

Current evidence suggests the etiology of inflammatory bowel diseases (IBD) involves the confluence of host genetic, environmental, and microbial factors that lead to chronic, and often refractory, disease in susceptible individuals. The involvement of microbial triggers in IBD, including Crohn's disease (CD), is increasingly evident with supporting data provided with advancements in metagenomic sequencing that have identified perturbations in microbial structure and function-broadly termed dysbiosis-in CD patients compared with healthy subjects. This concept is supported by the finding germ-free animals with CD genetic susceptibility fail to develop disease; demonstrating microorganisms are necessary but not sufficient for CD. The vast majority of CD microbiome research has focused on the complex bacterial communities and microbiome dysbiosis in the gut with 16S metagenomic sequencing. However, emerging data capturing eukaryotes suggest fungal opportunistic pathogens are also associated with IBD pathogenesis and chronicity. This hypothesis is further supported by historical observations that CD patient populations display elevated antibodies against fungal targets, even evident before disease diagnosis. This review discusses the current findings in the field, followed by historical and metagenomic evidence for fungal pathogens in the development and recurrence of CD in adult and pediatric populations.

Background and Aims Poor sleep quality in Crohn’s disease (CD) is associated with histologic activity and clinical relapse. We sought to characterize sleep dysfunction and determine the effect of poor sleep quality on risk for hospitalization and surgery. Methods Clinical data were collected for CD subjects including the Pittsburgh Sleep Quality Index (PSQI) and Harvey-Bradshaw index (HBI). The PSQI score and a brief medical history were obtained for control subjects. The PSQI and HBI correlation was tested at an initial clinic visit and at follow-up. Crohn’s disease subjects with and without poor sleep were compared for risk of hospitalization or surgery by Kaplan–Meier and Cox proportional hazards. Results Ninety-two CD and 82 control subjects were included. Crohn’s disease and control subjects shared similar baseline characteristics and PSQI (8.3 vs 7.8, P = 0.31), and 77% of the CD population had PSQI &gt;5. Crohn’s disease subjects with PSQI &gt;5 more often had inflammatory phenotypes and reported increased benzodiazepine and psychiatric medication use. Crohn’s disease subjects with PSQI &gt;5 also reported more night awakenings due to pain and bathroom use. The PSQI correlated with HBI (r = 0.256, P = 0.014), and ΔPSQI on follow-up correlated with ΔHBI (r = 0.47, P = 0.002). Cox proportional hazards model for hospitalization or surgery showed that PSQI &gt;8 was predictive of surgery or hospitalization (hazards ratio 5.37; 95% confidence interval, 1.39–27.54). Conclusion There is a high burden of poor sleep quality in CD, which is associated with risk for adverse outcomes. Sleep quality may identify CD patients at risk for complications and have prognostic value in CD.

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As biologic-based medication options for ulcerative colitis expand, our understanding of their optimal use in clinical practice is advancing as well. The appropriate use of combination therapy with immunomodulators can reduce the immunogenicity of biologic agents and raise serum drug levels of the biologic. A treat-to-target strategy with objective assessments of disease activity clearly defines the goals of biologic drug treatment. Mucosal healing is an evolving treatment goal and is associated with long-term remission and reduced incidence of colectomy. Furthermore, regular reassessments and therapeutic drug monitoring can allow clinicians to make evidence-based changes in therapy. Biologic drug deescalation or re-initiation are less well developed topics, but are emerging areas of study. We review the evidence underlying these advances and a modern approach to the use of biologic therapy in ulcerative colitis.

The development of therapeutic antibodies represents a revolutionary change in medical therapy for digestive diseases. Beginning with the initial studies that confirmed the pathogenicity of cytokines in inflammatory bowel disease, the development and application of therapeutic antibodies brought challenges and insights into their potential and optimal use. Infliximab was the first biological drug approved for use in Crohn's disease and ulcerative colitis. The lessons learned from infliximab include the importance of immunogenicity and the influence of pharmacokinetics on disease response and outcomes. Building on this foundation, other therapeutic antibodies achieved approval for inflammatory bowel disease and many more are in development for several digestive diseases. In this review, we reflect on the history of therapeutic antibodies and discuss current practice and future directions for the field.