Correlation of 18F-FDG PET/MRE Metrics with Inflammatory Biomarkers in Patients with Crohn’s Disease: A Pilot Study

Background. To investigate the association between 18F-FDG (Fluorodeoxyglucose) PET (positron emission tomography)/MRE (magnetic resonance enterography) metrics with the inflammatory biomarkers fecal calprotectin and C-reactive protein (CRP) in patients with Crohn’s disease (CD). Methods. This prospective pilot study was institutional review board (IRB) approved with informed consent obtained. Consecutive CD patients were referred to 18F-FDG PET/MRE. Patients in whom colonoscopy was performed and CRP and fecal calprotectin levels were measured were included. CRP and fecal calprotectin were regarded as positive for inflammation if they were greater than 0.5 mg/dl and 150 mcg/g, respectively. Correlation of quantitative variables was performed using the Pearson’s correlation coefficient. Receiver operating characteristic (ROC) curves were drawn and the area under the curve (AUC) was calculated to evaluate the accuracy of PET and MRE metrics in determining the presence of inflammation evaluated by calprotectin and CRP levels. Results. Analysis of 21 patients (16 women and 5 men, 43±18 years) was performed. Magnetic resonance index of activity (MaRIA) score had an AUC of 0.63 associated with fecal calprotectin and CRP. Adding apparent diffusion coefficient (ADC) and metabolic inflammatory volume (MIV) to MaRIA score resulted in an AUC of 0.92 with a cutoff value of 447 resulting in 83% and 100% sensitivity and specificity, respectively. Conclusion. The addition of ADC and MIV to the MaRIA score increases the accuracy for discrimination of disease activity in patients with CD. Trial registration number is 2015062

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 Mi-crobial (CCC-GEM) cohort of healthy first-degree relatives of patients with Crohn's disease. Gut barrier function was assessed using the urinary fractional excretion of lactulose-to-mannitol ra-tio (LMR). Microbiome composition was assessed by sequencing fecal 16S ribosomal RNA. The cohort was divided into a discovery cohort (n = 2472) and a validation cohort (n = 655). A regression model was used to assess microbial associations with the LMR. A random forest classifier algorithm was performed to assess mi-crobial community contribution to barrier function. RESULTS: Individuals with impaired barrier function (LMR >0.025) had reduced alpha-diversity (Chao1 index, P = 4.0e-4) and altered beta-diversity (Bray-Curtis dissimilarity index, R2 = 0.001, P = 1.0e-3) compared with individuals with an LMR 0.025 (q < 0.05). Four genera (decreased prevalence of Adlercreutzia, Clostridia UCG 014, and Clostridium sensu stricto 1 and increased abundance of Colidextribacter) and 8 pathways (including decreased biosyn-thesis of glutamate, tryptophan, and threonine) were replicated in the validation cohort. The random forest approach revealed that the bacterial community is associated with gut barrier function (area under the curve, 0.63; P=1.4e-6). CONCLUSIONS: The gut microbiome community and pathways are associated with changes in gut barrier function. These findings may identify potential microbial targets to modulate gut barrier

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. Our objectives were to identify dietary patterns and assess whether they are associated with alterations in specific gut microbial compositions and subclinical levels of gut inflammation in a cohort of healthy first-degree relatives (FDRs) of patients with CD. METHODS: As part of the Genetic, Environmental, Microbial (GEM) Project, we recruited a cohort of 2289 healthy FDRs of patients with CD. Individuals provided stool samples and answered a validated food frequency questionnaire reflecting their habitual diet during the year before sample collection. Unsupervised analysis identified 3 dietary and 3 microbial composition clusters. RESULTS: DC3, resembling the Mediterranean diet, was strongly associated with a defined microbial composition, with an increased abundance of fiber-degrading bacteria, such as Ruminococcus, as well as taxa such as Faecalibacterium. The DC3 diet was also significantly associated with lower levels of subclinical gut inflammation, defined by fecal calprotectin, compared with other dietary patterns. No significant associations were found between individual food items and fecal calprotectin, suggesting that long-term dietary patterns rather than individual food items contribute to subclinical gut inflammation. Additionally, mediation analysis demonstrated that DC3 had a direct effect on subclinical inflammation that was partially mediated by the microbiota. CONCLUSIONS: Overall, these results indicated that Mediterranean-like dietary patterns are associated with microbiome and lower intestinal inflammation. This study will help guide future dietary strategies that affect microbial composition and host gut inflammation to prevent diseases

Autoimmune pancreatitis in patients with inflammatory bowel disease - a real-world multicentre collaborative ECCO CONFER study

Autoimmune pancreatitis (AIP) is rarely associated with inflammatory bowel disease (IBD). Long-term outcomes of AIP and IBD in patients with AIP-IBD coexistence and predictors of complicated AIP course are scarcely known. An ECCO COllaborative Network For Exceptionally Rare case reports project (ECCO-CONFER) collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD. We included 96 patients (53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35±16 years). The majority of Crohn's disease (CD) cases (78%) had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. 82% of patients were treated with steroids for AIP, the majority of which (91%) responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 (26%) individuals. In a multivariate model, younger age at AIP diagnosis (OR=1.05, P=0.008), family history of IBD (OR=0.1, P=0.03) and CD diagnosis (OR=0.2, P=0.04) were associated with uncomplicated AIP course. No IBD or AIP-related deaths occurred. In this large international cohort of patients with concomitant AIP-IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, however, one-quarter develop pancreatic complications. Age, familial history of IBD and CD may predict uncomplicated AIP course

Environmental Factors Associated with Risk of Crohn’s Disease Development in the CCC-GEM Project

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. We studied 4,289 healthy first-degree relatives (FDRs) of CD patients from the Crohn's and Colitis Canada - Genetic, Environmental, Microbial (CCC-GEM) project. Regression models identified environmental factors associated with future CD onset and their association with pre-disease biological factors, including altered intestinal permeability measured by urinary fractional excretion of lactulose to mannitol ratio(LMR); gut inflammation via fecal calprotectin(FCP) levels; and fecal microbiome composition through 16S rRNA sequencing. Over a 5.62-year median follow-up, 86 FDRs developed CD. Living with a dog between ages 5-15 (HR=0.62; 95% CI=0.40-0.96; P = .034), and living with a large family size in the first year of life (HR=0.43; 95% CI=0.21-0.85; P = .016) were associated with decreased CD risk; whereas having a bird at the time of recruitment (HR=2.78; CI=1.36-5.68; P = .005) was associated with an increased CD risk. Furthermore, living with a dog was associated with reduced LMR, altered relative abundance of multiple bacterial genera, and increased Chao1 diversity; while bird owners had higher FCP levels. Large family during participants' first year of life was associated with altered microbiota composition without affecting FCP or LMR. This study identifies environmental variables associated with CD risk. These variables were also associated with altered barrier function, subclinical inflammation, and gut microbiome composition shifts, suggesting potential roles in CD pathogenesis