Metabolomics reveal distinct molecular pathways associated with future risk of Crohn's Disease.

Host - microbiome interactions are central to Crohn'sdisease (CD) pathogenesis; yet the early metabolic alterations that precededisease onset remain poorly defined. To explore preclinical metabolicsignatures of CD, we analyzed baseline serum metabolomic profiles in a nestedcase-control study within the Crohn's and Colitis Canada - Genetics, Environment, Microbiome (CCC-GEM) Project, a prospective cohort of 5,122 healthyfirst-degree relatives (FDRs) of CD patients. We included 78 individuals wholater developed CD and 311 matched FDRs who remained disease-free.

Isoperistaltic Anastomosis Increases Neo-Terminal Ileum Intubation Rates in Crohn's Disease Patients.

Introduction: Side-to-side stapled ileocolonic anastomosis (ICA) is commonly used in Crohn's disease (CD). Antiperistaltic ICA (APICA) and isoperistaltic ICA (IPICA) alignments differ in ease of neo-terminal ileum (neo-TI) intubation, potentially impacting endoscopic follow-up. This study compares postsurgical neo-TI intubation feasibility between APICA and IPICA.

Isolated Anastomotic Ulcers Are Associated with a Higher Long-Term Risk for Postoperative Recurrence and a Differential Mucosa-Associated Microbiome Composition in Patients with Crohn's Disease Following Ileocolic Resection.

Background: The clinical relevance and underlying mechanism of isolated anastomotic ulcers (IAUs) following ileocolic resection (ICR) in patients with Crohn's disease (CD) are poorly understood. This study aimed to assess the postoperative recurrence (POR) risk and the mucosa-associated microbiome composition in CD patients with or without IAUs among those with a healthy neo-terminal ileum (TI).

Methods: CD patients who underwent ICR and without any ulcerations in the neo-TI (SES-CD ≤2) at first postoperative ileocolonoscopy were identified from an ongoing prospective multicenter study.

Deep phenotyping of health-disease continuum in the Human Phenotype Project.

The Human Phenotype Project (HPP) is a large-scale deep-phenotype prospective cohort. To date, approximately 28,000 participants have enrolled, with more than 13,000 completing their initial visit. The project is aimed at identifying novel molecular signatures with diagnostic, prognostic and therapeutic value, and at developing artificial intelligence (AI)-based predictive models for disease onset and progression.

Smokers with Crohn's face worse surgical outcomes: A 90-day perioperative analysis.

Objective: Smoking is associated with increased severity and recurrence of Crohn's disease (CD), but its impact on perioperative outcomes is unclear. This study evaluated the association between smoking and 90-day postoperative complications in patients with CD undergoing abdominal surgery.

Methods: We conducted a retrospective cohort study (2017-2019) of 294 patients with CD who underwent abdominal surgery.

High Ultra-Processed Food Consumption Is Associated with Clinical Exacerbation in Patients with Crohn's Disease in Remission: A Prospective Cohort Study.

Introduction: Diet can impact the clinical course of Crohn's disease (CD). However, the importance of food processing level is uncertain. We aimed to evaluate whether ultra-processed foods (UPFs) are associated with an increased risk of relapse among patients with CD in clinical remission.

Diagnosis and Management of Upper Gastrointestinal Involvement in Adult Patients With Crohn's Disease: A Systematic Review.

Background & Aims: The diagnosis and management of ileocolonic Crohn's disease are well-established. In contrast, standardized guidance pertaining to the diagnosis and management of upper gastrointestinal Crohn's disease (UGICD) is lacking, despite its potentially severe consequences. This comprehensive systematic review describes the prevalence, clinical presentation, and medical and surgical management of involvement of the upper GI tract in adult patients with Crohn's disease.

A Mushroom Based Prebiotic Supplement Pilot Study Among Patients with Crohn's Disease.

Data on a mushroom based prebiotic supplementation in patients with Crohn's disease (CD) in western population is scarce. In this pilot trial, we aimed to assess the clinical efficacy and fecal microbial compositional and functional alterations associated with 'Mycodigest,' a commercial prebiotic supplement composed of three mushroom extracts. Patients with mild to moderate CD were recruited to a single center, randomized, double-blind, placebo-controlled pilot induction trial.

Bronchiectasis in Patients With Inflammatory Bowel Diseases: Prevalence, Predictors, and Clinical Characteristics.

Background: Inflammatory bowel diseases (IBDs) are known to be associated with bronchiectasis (BE). However, data on patients with inflammatory bowel disease-related bronchiectasis (IBD-BE) are limited.

Research Question: What are the prevalence, risk factors, and clinical characteristics of IBD-BE?

Study Design And Methods: This was a single-center retrospective study including patients who visited an IBD unit at a tertiary center between 2022 and 2023.

Environmental risk factors of inflammatory bowel disease: toward a strategy of preventative health.

The pathogenesis of inflammatory bowel disease (IBD) involves a complex interplay between genetic, environmental, and microbial factors. Many of these environmental determinants are modifiable, offering opportunities to prevent disease or delay its onset. Advances in the study of preclinical IBD cohorts offer the potential to identify biomarkers that predict individuals at high risk of developing IBD, enabling targeted environmental interventions aimed at reducing IBD incidence.

Understanding Predictors of Crohn's Disease: Determinants of Altered Barrier Function in Pre-Disease Phase of Crohn's Disease.

The pathogenesis of Crohn's disease (CD) remains unknown. The current working theory is that genetic susceptibility influences host-microbe interactions, resulting in chronic inflammation. Case-control studies fail to explain the triggers or pathogenesis of the disease, notably due to confounding factors in patients with established disease.

Healthy First-Degree Relatives From Multiplex Families vs Simplex Families Have Higher Subclinical Intestinal Inflammation, a Distinct Fecal Microbial Signature, and Harbor a Higher Risk of Developing Crohn's Disease.

Background & Aims: Unaffected first-degree relatives (FDRs) from families with ≥2 affected FDRs with Crohn's disease (CD, multiplex families) have a high risk of developing CD, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between FDRs from multiplex vs simplex families and investigate the risk of future CD onset accounting for potential confounders.

Methods: We assessed the Crohn's and Colitis Canada Genetic Environmental Microbial cohort of healthy FDRs of patients with CD.

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.

Environmental Factors Associated With Risk of Crohn's Disease Development in the Crohn's and Colitis Canada - Genetic, Environmental, Microbial Project.

Background & Aims: To date, it is unclear how environmental factors influence Crohn's disease (CD) risk and how they interact with biological processes. This study investigates the association between environmental exposures and CD risk and evaluates their association with pre-disease biomarkers.

Methods: We studied 4289 healthy first-degree relatives (FDRs) of patients with CD from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project.

Faecal Transplantation for Ulcerative Colitis From Diet Conditioned Donors Followed by Dietary Intervention Results in Favourable Gut Microbial Profile Compared to Faecal Transplantation Alone.

Background And Aims: Several faecal microbial transplantation [FMT] approaches for ulcerative colitis [UC] have been investigated with conflicting results. We have recently published the clinical outcomes from the CRAFT UC Trial using FMT with the UC Exclusion Diet [UCED], compared with FMT alone. Here we aimed to compare the two FMT strategies in terms of microbial profile and function.

Autoimmune Pancreatitis in Patients with Inflammatory Bowel Disease: A Real-World Multicentre Collaborative ECCO CONFER Study.

Background: Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP-IBD and predictors of complicated AIP course have rarely been reported.

Methods: An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD.

Immune response and barrier dysfunction-related proteomic signatures in preclinical phase of Crohn's disease highlight earliest events of pathogenesis.

Objective: The measure of serum proteome in the preclinical state of Crohn's disease (CD) may provide insight into biological pathways involved in CD pathogenesis. We aimed to assess associations of serum proteins with future CD onset and with other biomarkers predicting CD risk in a healthy at-risk cohort.

Design: In a nested case-control study within the Crohn's and Colitis Canada Genetics Environment Microbial Project (CCC-GEM) cohort, which prospectively follows healthy first-degree relatives (FDRs), subjects who developed CD (n=71) were matched with four FDRs remaining healthy (n=284).

Altered Gut Microbiome Composition and Function Are Associated With Gut Barrier Dysfunction in Healthy Relatives of Patients With Crohn's Disease.

Background & Aims: The gut microbiome has been suggested to play a role in gut barrier hemostasis, but data are scarce and limited to animal studies. We therefore aimed to assess whether alterations in gut microbial composition and functional pathways are associated with gut barrier function in a cohort of healthy first-degree relatives of patients with Crohn's disease.

Methods: We used the Crohn's and Colitis Canada Genetic Environmental Microbial (CCC-GEM) cohort of healthy first-degree relatives of patients with Crohn's disease.

Mediterranean-Like Dietary Pattern Associations With Gut Microbiome Composition and Subclinical Gastrointestinal Inflammation.

Background & Aims: Case-control studies have shown that patients with Crohn's disease (CD) have a microbial composition different from healthy individuals. Although the causes of CD are unknown, epidemiologic studies suggest that diet is an important contributor to CD risk, potentially via modulation of bacterial composition and gut inflammation. We hypothesized that long-term dietary clusters (DCs) are associated with gut microbiome compositions and gut inflammation.

The Crohn's disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn's disease (CDED-AD): an open-label, pilot, randomised trial.

Background: The Crohn's disease exclusion diet (CDED) with partial enteral nutrition is effective for induction of remission in children with mild-to-moderate Crohn's disease. We aimed to assess the CDED in adults with Crohn's disease.

Methods: We did an open-label, pilot randomised trial at three medical centres in Israel.

Anti-Microbial Antibody Response is Associated With Future Onset of Crohn's Disease Independent of Biomarkers of Altered Gut Barrier Function, Subclinical Inflammation, and Genetic Risk.

Background And Aims: Altered host immune reactivity to microbial antigens is hypothesized to trigger the onset of Crohn's disease (CD). We aimed to assess whether increased serum anti-microbial antibody response in asymptomatic first-degree relatives (FDRs) of CD patients is an independent risk factor for future CD development.

Methods: We measured host serum antibody response to 6 microbial antigens at enrollment (Prometheus enzyme-linked immunosorbent assay test: anti-Saccharomyces cerevisiae antibodies immunoglobulin A/immunoglobulin G, anti-OmpC, anti-A4-Fla2, anti-FlaX, anti-CBir1) and derived the sum of positive antibodies (AS).