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Background Most Crohn’s disease [CD] patients require surgery. Ileitis recurs after most ileocolectomies and is a critical determinant for outcomes. The impacts of ileocolectomy-induced bile acid [BA] perturbations on intestinal microbiota and inflammation are unknown. We characterized the relationships between ileocolectomy, stool BAs, microbiota and intestinal inflammation in inflammatory bowel disease [IBD]. Methods Validated IBD clinical and endoscopic assessments were prospectively collected. Stool primary and secondary BA concentrations were compared based on ileocolectomy and ileitis status. Primary BA thresholds for ileitis were evaluated. Metagenomic sequencing was use to profile microbial composition and function. Relationships between ileocolectomy, BAs and microbiota were assessed. Results In 166 patients, elevated primary and secondary BAs existed with ileocolectomy. With ileitis, only primary BAs [795 vs 398 nmol/g, p = 0.009] were higher compared to without ileitis. The optimal primary BA threshold [≥228 nmol/g] identified ileitis on multivariable analysis [odds ratio = 2.3, p = 0.04]. Microbial diversity, Faecalibacterium prausnitzii and O-acetylhomoserine aminocarboxypropyltransferase [MetY] were decreased with elevated primary BAs. Amongst ileocolectomy patients, only those with elevated primary BAs had diversity, F. prausnitzii and MetY reductions. Those with both ileocolectomy and intermediate [p = 0.002] or high [≥228 nmol/g, p = 9.1e-11]] primary BA concentrations had reduced F. prausnitzii compared to without ileocolectomy. Those with ileocolectomy and low [ Conclusions Elevated primary BAs were associated with ileitis, and reduced microbial diversity, F. prausnitzii abundance and enzymatic abundance of MetY [acetate and l-methionine-producing enzyme expressed by F. prausnitzii], and were the only factors associated with these findings after ileocolectomy.

Background Although patients with inflammatory bowel disease (IBD) reported an increased frequency of gastrointestinal (GI) symptoms following infection, the durable impact of COVID-19 on underlying IBD is not well defined. Methods In 118 IBD patients with COVID-19, clinical and endoscopic IBD activity, laboratory markers (ESR, CRP, hemoglobin (Hb), fecal calprotectin(FCP)), and medication utilization was assessed up to 6 months post-infection and compared to during infection or up to 6 months prior to infection. Active disease was defined by a Harvey Bradshaw Index > 4, Mayo Score ≥2, SES-CD ≥2, Mayo endoscopic score ≥1. 16S rRNA analysis was used to evaluate microbiome composition in a subset of 12 patients before and after COVID-19. Results Although upper respiratory (86.6%) and new GI symptoms (39.1%) were common in patients with IBD, there was no significant change in IBD clinical disease activity (Pre vs. Post-COVID-19 HBI: 4.7 vs. 4.9; partial Mayo: 3.0 vs. 2.1), endoscopic evaluation (Pre vs. Post-COVID-19 SES-CD: 7.2 vs. 8.9, Mayo endoscopic score: 1.5 vs. 1.7), or laboratory markers (Pre vs. Post-COVID-19 CRP: 1.2 vs. 1.3; ESR: 25 vs. 26; Hb 12.8 vs. 13.2; FCP: 388 vs. 250) up to 7 months post-COVID-19 compared to the 6 months prior to infection (Table 1). Overall active disease was present in 60% of the cohort prior to COVID-19 and 55% and 59% during and post-COVID-19, respectively. More subjects (8.5%) reported a delay in medical therapy during COVID-19, but there were no differences in the need for corticosteroids, a change in medical therapy, or IBD-related surgery or hospitalization during or post-COVID-19 compared to the prior 6 months. Microbiome composition stratified by underlying IBD disease activity, but did not show significant change post-COVID-19 (Figure 1). Conclusion COVID-19 showed no durable impact on clinical IBD disease activity or microbiome composition supporting guidelines for continued maintenance care.

Background: The FUT2 gene encodes fucosyltransferase 2 (FUT2), regulating intestinal antigen secretion and bacterial adherence. FUT2 homozygous mutations (FUT2M) and subsequent non-secretor status is associated with Crohn's disease (CD). A nucleotide polymorphism encoding a nonsense variant may predispose to CD by disrupting bacterial adherence or mucin fucosylation. This alters bacterial and mucous protection against pathogens, causing immune disequilibrium and mucosal inflammation. FUT2 products also interact with the IL 12/23 inflammatory pathways. Supporting genome wide association studies strongly associate homozygous FUT2 SNPs in strong linkage disequilibrium (LD) (rs602662 (A), rs676388 (C), rs492602 (G), rs504963 (A), rs601338 (A), rs485186 (G)), non-secretion, and CD. rs601338 (W143X) is the common null allele in Caucasians associated with the ABO non-secretory phenotype. Methods: We conducted a cross-sectional observational study of consecutive adult CD outpatients at the McGill University Health Center (2013–2015). Clinical and biochemical data were prospectively collected at a single routine office visit. We analyzed associations between CD and FUT2 mutation status. Results: Sixty-two CD patients were recruited. FUT2M homozygotes (rs602662, rs601338 or any mutation in LD) were detected in 27% of CD (17/62). Compared to Wild type (n=18), CD FUT2M homozygotes (n=17) had less penetrating CD (18% vs. 56%, p=0.02) and higher clinical remission without biologic or immunomodulator therapy (47% vs 6%, p=0.006). The latter was not observed in heterozygotes (22%, n=27, p=0.15). CD FUT2M homozygotes had similar disease location in the ileum (L2 p=0.31) and colon (L1, L3, p=0.56). Similarly, patients with homozygous rs601338 (n=15) had increased clinical remission rates without biologic or immunomodulator therapy (53% vs 5%, p=0.0016) compared to patients with wild type status (n=19). This was not observed in heterozygotes (24%, n=25, p=0.09). Both rs601338 homozygotes (20%) and heterozygotes (24%) had less penetrating disease than Wild type (53%, p=0.0495, 0.0478). rs601338 homozygotes (67%) but not heterozygotes (56%) had more luminal phenotype compared to non-mutants (32%, p=0.042). Conclusions: FUT2 homozygous mutations in CD was associated with a milder disease course: lower rates of penetrating disease and higher rates of remission without need for biologic or immunomodulator therapy. FUT2 may play a role in the natural history of CD through mofification of expression of adherence molecules and gut dysbiosis. Further studies are needed to confirm these findings.