Inflammatory bowel disease associated with primary sclerosing cholangitis is associated with an altered gut microbiome and bile acid profile.

Background: Primary sclerosing cholangitis associated with inflammatory bowel disease (IBD-PSC) carries significant morbidity compared to IBD without PSC. Alterations in microbial composition and bile acid (BA) profiles have been shown to modulate chronic inflammation in IBD, but data in IBD-PSC is scarce. We aimed to assess the differences in gut microbiome composition as well as in the BA profile and BA-related microbial functions between IBD-PSC and IBD-only.

After Surgically Induced Remission, Ileal and Colonic Mucosa-Associated Microbiota Predicts Crohn's Disease Recurrence.

Background & Aims: Investigating the tissue-associated microbiota after surgically induced remission may help to understand the mechanisms initiating intestinal inflammation in Crohn's disease.

Methods: Patients with Crohn's disease undergoing ileocolic resection were prospectively recruited in 6 academic centers. Biopsy samples from the neoterminal ileum, colon, and rectosigmoid were obtained from colonoscopies performed after surgery.

Clinical Predictors of Early and Late Endoscopic Recurrence Following Ileocolonic Resection in Crohn's Disease.

Background And Aims: Multiple factors are suggested to place Crohn's disease patients at risk of recurrence after ileocolic resection with conflicting associations. We aimed to identify clinical predictors of recurrence at first [early] and further [late] postoperative colonoscopy.

Methods: Crohn's disease patients undergoing ileocolic resection were prospectively recruited at six North American centres.

Third and Fourth Vaccine Doses Broaden and Prolong Immunity to SARS-CoV-2 in Adult Patients with Immune-Mediated Inflammatory Diseases.

Previous studies have reported impaired humoral responses after SARS-CoV-2 mRNA vaccination in patients with immune-mediated inflammatory diseases (IMIDs), particularly those treated with anti-TNF biologics. We previously reported that IMID patients diagnosed with inflammatory bowel disease, psoriasis, psoriatic arthritis, ankylosing spondylitis, or rheumatoid arthritis exhibited greater waning of Ab and T cell responses than healthy control subjects after SARS-CoV-2 vaccine dose 2. Fewer data are available on the effects of third and fourth doses.

Accelerated waning of immunity to SARS-CoV-2 mRNA vaccines in patients with immune-mediated inflammatory diseases.

BACKGROUNDLimited information is available on the impact of immunosuppressants on COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID).METHODSThis observational cohort study examined the immunogenicity of SARS-CoV-2 mRNA vaccines in adult patients with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, or psoriatic disease, with or without maintenance immunosuppressive therapies. Ab and T cell responses to SARS-CoV-2, including neutralization against SARS-CoV-2 variants, were determined before and after 1 and 2 vaccine doses.

Combined Histo-endoscopic Remission but not Endoscopic Healing Alone in Ulcerative Colitis is Associated with a Mucosal Transcriptional Profile Resembling Healthy Mucosa.

Background And Aims: A composite endpoint of histological and endoscopic remission is proposed to be the most complete measure of mucosal healing in ulcerative colitis [UC]. We aim to establish the prognosis, and transcriptional and microbial features of histo-endoscopic remission and activity.

Methods: A cross-sectional endoscopic rectosigmoid colon sample collection from UC patients and healthy controls [HC] was performed for histopathology and host genome-wide RNA-sequencing.

Integrative Analysis of Colonic Biopsies from Inflammatory Bowel Disease Patients Identifies an Interaction Between Microbial Bile Acid-inducible Gene Abundance and Human Angiopoietin-like 4 Gene Expression.

Background And Aims: Microbial-derived bile acids can modulate host gene expression, and their faecal abundance is decreased in active inflammatory bowel disease [IBD]. We analysed the impact of endoscopic inflammation on microbial genes involved in bile acid biotransformation, and their interaction with host transcriptome in the intestinal mucosa of IBD patients.

Methods: Endoscopic mucosal biopsies were collected from non-inflamed and inflamed terminal ileum, ascending and sigmoid colon of IBD patients.

Conducting Translational Gastrointestinal Research in the Era of COVID-19.

Spread of the novel coronavirus SARS-CoV-2 has resulted in a global pandemic that is affecting the health and economy of all World Health Organization [WHO] regions. Clinical and translational research activities have been affected drastically by this global catastrophe. In this document we provide a suggested roadmap for resuming gastrointestinal translational research activities, emphasising physical distancing and use of personal protective equipment.

Persistent Diarrhea in Patients With Crohn's Disease After Mucosal Healing Is Associated With Lower Diversity of the Intestinal Microbiome and Increased Dysbiosis.

Background & Aims: In patients with inflammatory bowel diseases (IBDs), symptoms do not always associate with the severity of endoscopic inflammation and can persist after mucosal healing. We investigated whether symptoms in patients with successfully treated IBD are related to the composition of the intestinal microbiome.

Methods: We analyzed 590 tissue biopsy specimens from 215 patients with IBD and 48 healthy individuals (controls).

Identification of Target Golimumab Levels in Maintenance Therapy of Crohn's Disease and Ulcerative Colitis Associated With Mucosal Healing.

Introduction: Golimumab is approved as a therapy for ulcerative colitis (UC) patients. Recent data also demonstrate efficacy in Crohn's disease (CD); however, little is known about target drug levels to achieve endoscopic remission.

Methods: We performed a retrospective analysis of IBD patients on maintenance golimumab.

The Unsolved Link of Genetic Markers and Crohn's Disease Progression: A North American Cohort Experience.

Background: While progress has been made in the identification of Crohn's disease (CD) susceptibility loci, efforts to identify a genetic basis for disease progression have been less fruitful. The specific aim of this study was to build upon the major genetic advances made in IBD by applying genome-wide technologies toward predicting disease progression in CD.

Methods: Crohn's disease cases (n = 1495) from 3 IBD centers were reviewed by experienced physicians.

Stricturing and Fistulizing Crohn's Disease Is Associated with Anti-tumor Necrosis Factor-Induced Psoriasis in Patients with Inflammatory Bowel Disease.

Background: Paradoxical development of psoriasis in patients on anti-TNF agents has been increasingly reported.

Aim: The aim was to characterize the prevalence and clinical characteristics of anti-TNF-associated psoriasis in a large cohort of inflammatory bowel disease patients.

Methods: Medical records of patients with Crohn's disease or ulcerative colitis treated with anti-TNF therapy at a single, tertiary IBD center were identified between 2004 and 2016.

Therapeutic Drug Monitoring to Guide Infliximab Dose Adjustment is Associated with Better Endoscopic Outcomes than Clinical Decision Making Alone in Active Inflammatory Bowel Disease.

Background: Adequate infliximab (IFX) levels are associated with favorable outcomes in inflammatory bowel disease. Using therapeutic drug monitoring (TDM) to guide dosing is cost effective and associated with clinical improvement, but effect on endoscopic outcomes remains unclear.

Methods: Primary responders to IFX who underwent dose escalation (2008-2014) were reviewed.

A Pleiotropic Missense Variant in SLC39A8 Is Associated With Crohn's Disease and Human Gut Microbiome Composition.

Background & Aims: Genome-wide association studies have identified 200 inflammatory bowel disease (IBD) loci, but the genetic architecture of Crohn's disease (CD) and ulcerative colitis remain incompletely defined. Here, we aimed to identify novel associations between IBD and functional genetic variants using the Illumina ExomeChip (San Diego, CA).

Methods: Genotyping was performed in 10,523 IBD cases and 5726 non-IBD controls.

A Frameshift in CSF2RB Predominant Among Ashkenazi Jews Increases Risk for Crohn's Disease and Reduces Monocyte Signaling via GM-CSF.

Background & Aims: Crohn's disease (CD) has the highest prevalence in Ashkenazi Jewish populations. We sought to identify rare, CD-associated frameshift variants of high functional and statistical effects.

Methods: We performed exome sequencing and array-based genotype analyses of 1477 Ashkenazi Jewish individuals with CD and 2614 Ashkenazi Jewish individuals without CD (controls).

TNFRSF1B Is Associated with ANCA in IBD.

The genetic basis of antineutrophil cytoplasmic antibody, an important biomarker of inflammatory bowel disease (IBD), has never been thoroughly examined on a genome-wide scale. In this study, we performed a 2-stage genome-wide association study (GWAS) on antineutrophil cytoplasmic antibody in IBD cases. In the 2959 IBD cases in the discovery stage, we observed an association between a variant in the gene TNFRSF1B with antineutrophil cytoplasmic antibody level (rs5745994, minor allele frequency = 0.

Microbiome Heterogeneity Characterizing Intestinal Tissue and Inflammatory Bowel Disease Phenotype.

Inflammatory bowel disease has been associated with differential abundance of numerous organisms when compared to healthy controls (HCs); however, few studies have investigated variability in the microbiome across intestinal locations and how this variability might be related to disease location and phenotype. In this study, we have analyzed the microbiome of a large cohort of individuals recruited at Mount Sinai Hospital in Toronto, Canada. Biopsies were taken from subjects with Crohn's disease, ulcerative colitis, and HC, and also individuals having undergone ileal pouch-anal anastomosis for treatment of ulcerative colitis or familial adenomatous polyposis.

Infliximab to Treat Refractory Inflammation After Pelvic Pouch Surgery for Ulcerative Colitis.

Background: Inflammatory pouch complications refractory to first-line therapies remain problematic following ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). We evaluated infliximab efficacy and associations with therapeutic response.

Methods: Data from individuals who underwent colectomy and IPAA for UC (2000-2014) were reviewed.

Predictors of Outcome in Ulcerative Colitis.

Background: Approximately 80% of patients with ulcerative colitis (UC) have intermittently active disease and up to 20% will require a colectomy, but little data available on predictors of poor disease course. The aim of this study was to identify clinical and genetic markers that can predict prognosis.

Methods: Medical records of patients with UC with ≥5 years of follow-up and available DNA and serum were retrospectively assessed.

Higher Rates of Dose Optimisation for Infliximab Responders in Ulcerative Colitis than in Crohn's disease.

Background: Studies have demonstrated the benefit of dose optimisation in the setting of secondary loss of response to infliximab in inflammatory bowel disease.

Aim: The aim of our study was to retrospectively investigate the rates of dose optimisation in an inflammatory bowel disease cohort receiving maintenance infliximab therapy to determine if there are different rates of dose optimisation between CD and UC cases and what impact this has on the durability of treatment effect.

Methods: Cases receiving infliximab for treatment of IBD between January 2008 and February 2014 were identified from an infusion centre database.

Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease.

Background: Pouchitis is common after ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC). Similar to inflammatory bowel disease (IBD), both host genetics and the microbiota are implicated in its pathogenesis. We use the IPAA model of IBD to associate mucosal host gene expression with mucosal microbiomes and clinical outcomes.

Complex host genetics influence the microbiome in inflammatory bowel disease.

Background: Human genetics and host-associated microbial communities have been associated independently with a wide range of chronic diseases. One of the strongest associations in each case is inflammatory bowel disease (IBD), but disease risk cannot be explained fully by either factor individually. Recent findings point to interactions between host genetics and microbial exposures as important contributors to disease risk in IBD.

Downregulation of expression of xenobiotic efflux genes is associated with pelvic pouch inflammation in ulcerative colitis.

Background: As many as 50% of patients with ulcerative colitis who have undergone ileal pouch-anal anastomosis develop de novo inflammation in the ileal pouch after surgery. With the use of microarray technology, we investigated what gene expression changes occur in the pelvic pouch after surgery for ulcerative colitis and how these changes vary by pouch outcome.

Methods: Patients who had undergone ileal pouch-anal anastomosis and closure of ileostomy had biopsy specimens from the pouch and pre-pouch ileum prospectively collected.