Decreased Serum Tryptophan and Severe Ulcerative Damage of Colon Mucosa Identify Inflammatory Bowel Disease Patients With High Risk of Cytomegalovirus Colitis.

Introduction: Patients with inflammatory bowel disease (IBD) are predisposed to the reactivation of viral infections such as cytomegalovirus (CMV). Clinical discrimination of disease flares and colonic CMV reactivation is difficult in patients with established diagnosis of IBD, and there are no reliable noninvasive diagnostic tools yet. Furthermore, the influence of novel therapeutics including biologicals and Janus kinase inhibitors on the risk of CMV colitis is unclear.

Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic T1 cell responses in Crohn's disease.

Aberrant CD4 T cell reactivity against intestinal microorganisms is considered to drive mucosal inflammation in inflammatory bowel diseases. The disease-relevant microbial species and the corresponding microorganism-specific, pathogenic T cell phenotypes remain largely unknown. In the present study, we identified common gut commensal and food-derived yeasts, as direct activators of altered CD4 T cell reactions in patients with Crohn's disease (CD).

Interobserver Reliability of the Nancy Index for Ulcerative Colitis: An Assessment of the Practicability and Ease of Use in a Single-Centre Real-World Setting.

Background: Histological disease severity assessment in ulcerative colitis [UC] has become a mainstay in the definition of clinical endpoints ['histological remission'] in clinical trials of UC. Several scores have been established in the microscopic assessment of disease activity, but the Nancy index [NI] stands out as being the histological index with the fewest scoring items. To what extent histological assessment using the NI is affected by interobserver reliability in a real-word setting is poorly understood.

DNA methyltransferase 3A controls intestinal epithelial barrier function and regeneration in the colon.

Genetic variants in the DNA methyltransferase 3 A (DNMT3A) locus have been associated with inflammatory bowel disease (IBD). DNMT3A is part of the epigenetic machinery physiologically involved in DNA methylation. We show that DNMT3A plays a critical role in maintaining intestinal homeostasis and gut barrier function.

Longitudinal multi-omics analysis identifies early blood-based predictors of anti-TNF therapy response in inflammatory bowel disease.

Background And Aims: Treatment with tumor necrosis factor α (TNFα) antagonists in IBD patients suffers from primary non-response rates of up to 40%. Biomarkers for early prediction of therapy success are missing. We investigated the dynamics of gene expression and DNA methylation in blood samples of IBD patients treated with the TNF antagonist infliximab and analyzed the predictive potential regarding therapy outcome.

Distinct Longitudinal Changes in Immunoglobulin G N-Glycosylation Associate with Therapy Response in Chronic Inflammatory Diseases.

Immunosuppressants and biologicals are widely used therapeutics for various chronic inflammatory diseases (CID). To gain more detailed insight into their downstream effects, we examined their impact on serum immunoglobulin G (IgG) glycosylation. We analyzed IgG subclass-specific fragment crystallizable (Fc) N-glycosylation in patients suffering from various CID using the LC-MS approach.

Detailed Transcriptional Landscape of Peripheral Blood Points to Increased Neutrophil Activation in Treatment-Naïve Inflammatory Bowel Disease.

Background And Aims: Inflammatory bowel disease [IBD] is a chronic relapsing disorder of the gastrointestinal tract, which generally manifests as Crohn's disease [CD] or ulcerative colitis [UC]. These subtypes are heterogeneous in terms of disease location and histological features, while sharing common clinical presentation, genetic associations and, thus, common immune regulatory pathways.

Methods: Using miRNA and mRNA coupled transcriptome profiling and systems biology approaches, we report a comprehensive analysis of blood transcriptomes from treatment-naïve [n = 110] and treatment-exposed [n = 177] IBD patients as well as symptomatic [n = 65] and healthy controls [n = 95].

Humoral protection to SARS-CoV2 declines faster in patients on TNF alpha blocking therapies.

Background: The persistence of the SARS-CoV2 pandemic, partly due to the appearance of highly infectious variants, has made booster vaccinations necessary for vulnerable groups. Questions remain as to which cohorts require SARS-CoV2 boosters. However, there is a critical lack of data on the dynamics of vaccine responses in patients with chronic inflammatory diseases (CID) undergoing immunosuppressive/disease modifying anti-rheumatic (DMARD) treatment.

Therapeutic Interleukin-6 Trans-signaling Inhibition by Olamkicept (sgp130Fc) in Patients With Active Inflammatory Bowel Disease.

Background & Aims: A large unmet therapeutic need exists in inflammatory bowel disease (IBD). Inhibition of interleukin (IL)-6 appears to be effective, but the therapeutic benefit of a complete IL6/IL6 receptor (IL6R) blockade is limited by profound immunosuppression. Evidence has emerged that chronic proinflammatory activity of IL6 is mainly mediated by trans-signaling via a complex of IL6 bound to soluble IL6R engaging the gp130 co-receptor without the need for membrane-bound IL6R.

Metabolic Functions of Gut Microbes Associate With Efficacy of Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Diseases.

Background & Aims: Altered interactions between the mucosal immune system and intestinal microbiota contribute to pathogenesis of inflammatory bowel diseases (IBD). It is not clear how inhibitors of cytokines, such as antagonists of tumor necrosis factor (anti-TNF), affect the intestinal microbiome. We investigated the effects of anti-TNF agents on gut microbe community structure and function in a longitudinal 2-step study of patients with IBD.

Evaluation of interleukin-6 and its soluble receptor components sIL-6R and sgp130 as markers of inflammation in inflammatory bowel diseases.

Purpose: Interleukin-6 (IL-6) production and signalling are increased in the inflamed mucosa in inflammatory bowel diseases (IBD). As published serum levels of IL-6 and its soluble receptors sIL-6R and sgp130 in IBD are from small cohorts and partly contradictory, we systematically evaluated IL-6, sIL-6R and sgp130 levels as markers of disease activity in Crohn's disease (CD) and ulcerative colitis (UC).

Methods: Consecutive adult outpatients with confirmed CD or UC were included, and their disease activity and medication were monitored.

Vedolizumab is associated with changes in innate rather than adaptive immunity in patients with inflammatory bowel disease.

Objective: Vedolizumab, a monoclonal antibody directed against the integrin heterodimer α4β7, is approved for the treatment of Crohn's disease and ulcerative colitis. The efficacy of vedolizumab has been suggested to result from inhibition of intestinal T cell trafficking although human data to support this conclusion are scarce. We therefore performed a comprehensive analysis of vedolizumab-induced alterations in mucosal and systemic immunity in patients with inflammatory bowel disease (IBD), using anti-inflammatory therapy with the TNFα antibody infliximab as control.

Mucus Detachment by Host Metalloprotease Meprin β Requires Shedding of Its Inactive Pro-form, which Is Abrogated by the Pathogenic Protease RgpB.

The host metalloprotease meprin β is required for mucin 2 (MUC2) cleavage, which drives intestinal mucus detachment and prevents bacterial overgrowth. To gain access to the cleavage site in MUC2, meprin β must be proteolytically shed from epithelial cells. Hence, regulation of meprin β shedding and activation is important for physiological and pathophysiological conditions.

Increased Tryptophan Metabolism Is Associated With Activity of Inflammatory Bowel Diseases.

Background & Aims: Administration of tryptophan and some of its metabolites reduces the severity of colitis in mice, whereas removing tryptophan from the diet increases susceptibility to colitis. Transfer of the intestinal microbiome transfers the colitogenic phenotype from tryptophan starved animals to normally nourished mice. We aimed to systematically evaluate serum levels of tryptophan and its metabolites in patients with inflammatory bowel diseases (IBD), and study their association with clinical and serologic features.

Genome-wide association analysis for chronic venous disease identifies EFEMP1 and KCNH8 as susceptibility loci.

Chronic venous disease (CVD) is a multifactorial condition representing one of the most common disorders among populations of Western countries. The heritability of about 17% suggests genetic risk factors in CVD etiology. However, so far the genetic causes are unknown.

Combination therapy with vedolizumab and etanercept in a patient with pouchitis and spondylarthritis.

Inflammatory bowel disease is frequently associated with spondylarthritis (SpA). It has been discussed that α4/β7 expressing lymphocytes are involved in the aetiology of SpA. We report a case of a successful combination therapy of vedolizumab (VDZ) and etanercept (ETA) in a patient with ulcerative colitis with pouchitis and SpA.

Uncoupling of mucosal gene regulation, mRNA splicing and adherent microbiota signatures in inflammatory bowel disease.

Objective: An inadequate host response to the intestinal microbiota likely contributes to the manifestation and progression of human inflammatory bowel disease (IBD). However, molecular approaches to unravelling the nature of the defective crosstalk and its consequences for intestinal metabolic and immunological networks are lacking. We assessed the mucosal transcript levels, splicing architecture and mucosa-attached microbial communities of patients with IBD to obtain a comprehensive view of the underlying, hitherto poorly characterised interactions, and how these are altered in IBD.

Comparison of two exploratory dietary patterns in association with the metabolic syndrome in a Northern German population.

Diet is related to many chronic disease conditions such as the metabolic syndrome (MetS). We set out to compare behaviour-related with disease-related patterns and their association with the MetS in a German cross-sectional study. A total of 905 participants of a Northern German cohort (aged 25-82 years) completed a FFQ, underwent anthropometric assessments and provided a blood sample.

Parameters of a severe disease course in ulcerative colitis.

Aim: To detect high risk patients with a progressive disease course of ulcerative colitis (UC) requiring immunosuppressive therapy (IT).

Methods: A retrospective, multicenter analysis of 262 UC patients from eight German tertiary inflammatory bowel disease centres was performed. Patients were divided into two groups depending on the patients need to initiate immunosuppressive therapy in the disease course.

Diagnosing fatty liver disease: a comparative evaluation of metabolic markers, phenotypes, genotypes and established biomarkers.

Background: To date, liver biopsy is the only means of reliable diagnosis for fatty liver disease (FLD). Owing to the inevitable biopsy-associated health risks, however, the development of valid noninvasive diagnostic tools for FLD is well warranted.

Aim: We evaluated a particular metabolic profile with regard to its ability to diagnose FLD and compared its performance to that of established phenotypes, conventional biomarkers and disease-associated genotypes.