Faculty Bibliography

Inflammatory bowel diseases often require long-term treatment with advanced therapies, including biologics and small molecules. The use of these agents must be carefully balanced against the risks of uncontrolled gastrointestinal inflammation and the potential for treatment-related adverse events. This review synthesizes contemporary evidence on malignancy, infection, venous thromboembolism, and major adverse cardiovascular events in inflammatory bowel diseases, integrating risks attributable to underlying disease and those conferred by specific drug classes, with the goal of improving how clinicians communicate these risks to patients. Chronic intestinal inflammation increases the risk of colorectal cancer, small bowel adenocarcinoma, intestinal lymphoma, anal cancer in fistulizing Crohn's disease, and cholangiocarcinoma in those with primary sclerosing cholangitis, alongside modest excesses in select extraintestinal malignancies. Thiopurines increase the risk of lymphoma, particularly when combined with anti-tumor necrosis factor agents, and nonmelanoma skin cancer. Corticosteroid use is the major driver of serious infection, venous thromboembolism, and major adverse cardiovascular events, whereas combination anti-TNF-thiopurine therapy, Janus kinase inhibitors, and S1P receptor modulators are associated with therapy-specific and context-specific infectious and thrombotic risks, which remain low in absolute terms for most patients. Across outcomes, we emphasize absolute risk and patient-level modifiers, and provide pictorial tools that depict clinically meaningful risks to support shared decision-making and individualized, evidence-based risk communication with patients.

Clostridioides difficile infection (CDI) is a major cause of morbidity, mortality, and healthcare utilization worldwide. Although advances in antimicrobial stewardship and infection prevention have reduced healthcare-associated disease in some settings, the incidence of community-associated CDI and the persistent burden of recurrent CDI (rCDI) continue to pose substantial clinical challenges. Because recurrent disease is fundamentally driven by persistent disruption of the intestinal microbiome and loss of colonization resistance, prevention has emerged as the central strategy for reducing long-term disease burden. This review summarizes contemporary evidence supporting prevention of both incident and rCDI, emphasizing practical approaches for gastroenterologists. Primary prevention centers on minimizing modifiable risk factors through antimicrobial stewardship, infection prevention and control, diagnostic stewardship to distinguish colonization from infection, and strategies to preserve the intestinal microbiome. For patients with CDI, we review evidence supporting extended antibiotic regimens, oral vancomycin prophylaxis during subsequent systemic antibiotic exposure, and microbiome restoration therapies, including conventional fecal microbiota transplantation and US Food and Drug Administration-approved microbiota-based therapies, which have transformed secondary prevention by restoring microbial diversity and colonization resistance. Special consideration is given to populations at particularly high risk for recurrence, including older adults, immunocompromised individuals, transplant recipients, and patients with inflammatory bowel disease. Finally, we discuss emerging preventive strategies, including precision risk stratification, microbiome- and metabolome-based biomarkers, bile acid modulation, and approaches targeting asymptomatic colonization. Together, these advances signal a paradigm shift from treating CDI episodes to implementing personalized preventive strategies that interrupt the cycle of recurrent disease and improve long-term patient outcomes.

BACKGROUND/UNASSIGNED:Ulcerative colitis is monitored through clinical, laboratory, endoscopic, and histologic measures. Persistence of histologic inflammation despite clinical and endoscopic remission is associated with disease flare. METHODS/UNASSIGNED:We compared the identification of clinically significant histologic inflammation by general and IBD-specialized gastroenterologists (GI) using a simplified binary scoring system and looked at associations with disease relapse. RESULTS/UNASSIGNED:Both general and IBD-specialized GIs identified significant inflammation associated with relapse, though IBD-specialized GIs scoring had stronger correlations with relapse. CONCLUSIONS/UNASSIGNED:Our findings suggest simple histologic assessment can inform risk stratification, and further work is needed to optimize monitoring patients with histologic inflammation despite endoscopic remission.

BACKGROUND:Ulcerative colitis (UC) is characterized by chronic gastrointestinal inflammation often requiring corticosteroids, both of which may increase long-term cardiometabolic risk. Early colectomy, by eliminating these exposures, may mitigate this risk, though data are limited. METHODS:We performed a matched cohort study using the Swedish National Patient Register and ESPRESSO histopathology cohort, identifying individuals aged ≥18 with incident UC (2006-2021, follow-up through 2023). Patients who underwent total colectomy within two years of diagnosis (early colectomy) were matched 1:1 to those without early colectomy using propensity score matching. The primary outcome was incident cardiovascular disease (CVD), with type 2 diabetes mellitus (DM2) assessed as a secondary outcome. Kaplan-Meier and Cox proportional hazards models were used for analyses. RESULTS:Among 1,832 individuals (median age 45 years, 64.6% male, median post-matching follow-up of 9 years), early colectomy was associated with a significantly lower cumulative incidence of CVD on unadjusted Kaplan-Meier analysis (p=0.02). The CVD incidence rate was 9.1 per 1,000 person-years in the early colectomy group versus 13.0 in controls; after adjustment for baseline covariates, early colectomy was associated with a 32% lower risk of CVD, though this did not reach statistical significance (aHR 0.68, 95% CI 0.44-1.06). A numerically lower risk of DM2 was also observed (incidence rate: 5.5 vs 5.8 per 1,000 person-years; aHR 0.76, 95% CI 0.39-1.48); findings were consistent across sensitivity analyses. CONCLUSIONS:Early colectomy was associated with numerically lower risks of CVD and DM2 in UC, raising the possibility that earlier surgical intervention may mitigate long-term cardiometabolic risk beyond established IBD-related benefits, though confirmation in larger studies is needed.

BACKGROUND AND AIMS/OBJECTIVE:Absolute risk estimates of serious infections in inflammatory bowel disease (IBD) across therapies and concomitant corticosteroid treatment are limited. We aimed to assess serious infection risk in IBD patients receiving different therapies, with or without corticosteroids. METHODS:Using nationwide Swedish registers (2007-2024), we compared rates of serious infections in patients with IBD treated with different therapies versus matched population comparators (≤10 per patient), stratified by corticosteroid use. We also performed 1:1 propensity score (PS)-matching for direct comparison of infection risk in IBD with or without concomitant corticosteroids exposure across advanced therapies. Incidence rates and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were calculated. RESULTS:We identified 145,125 exposure periods in patients with IBD naïve to immunomodulators and advanced therapies, 82,675 to immunomodulators, and 90,181 to advanced therapies (TNF inhibitors with and without immunomodulator, anti-integrins, anti-interleukins, and JAK inhibitors). Across therapies, exposure periods with corticosteroids carried a higher risk of serious infections than periods without, both compared to the general population (incidence rate difference range=3.6-10.2/100 person-years; aHR range=4.52-15.86) and in PS-matched within therapy group comparisons (incidence rate difference range=3.9-8.5/100 person-years; aHR=1.82-3.60). Relative risk was highest in children and increased with cumulative corticosteroid dose. CONCLUSION/CONCLUSIONS:Patients with IBD receiving corticosteroids had significantly higher rates of serious infections compared with those not receiving corticosteroids across therapies, with rate differences across age groups and combinations of treatments. These data will inform infection risk assessment and consideration of individualized infection-prevention strategies.

BACKGROUND:Biologic prophylaxis is used to prevent postoperative recurrence (POR) of Crohn's disease (CD) in high-risk patients who have undergone ileocolonic resection (ICR). There are limited data to guide clinicians' choice of prophylactic biologic class to prevent POR in patients previously exposed to biologics. We aimed to determine if reutilizing a prophylactic biologic class is associated with lower risk of POR in patients preoperatively exposed to biologics. METHODS:Adult CD patients who underwent ICR between 2009 and 2020 and were ever preoperatively exposed to biologics were included. Composite POR, including endoscopic (Rutgeerts ≥ i2b) and/or radiographic recurrence, was compared between patients who: received no prophylaxis, reutilized prophylaxis, or received a new class of prophylaxis (≤3 months from ICR) using Kaplan-Meier analysis. A multivariate Cox proportional hazards regression model was utilized to compare the 3 groups along with clinically established risk factors. RESULTS:A total of 635 biologic-exposed patients (≥2 biologics: 46%) who postoperatively received no prophylactic biologic (63.8%), who reutilized prophylactic biologic (30.7%), or who received a new class of prophylactic biologic (5.5%) were included. On multivariable analysis, no biologic prophylaxis was associated with a higher risk of recurrence (adjusted hazard ratio, 1.33; 95% confidence interval, 1.01-1.74; P = .04), and new biologic prophylaxis (adjusted hazard ratio, 1.50; 95% confidence interval, 0.89-2.53; P = .13) was associated with a similar risk of recurrence when compared with reutilization. Recurrence-free survival was similar among the 3 groups (P = .08); however, in patients undergoing their first ICR (P = .026) and in patients previously exposed only to anti-tumor necrosis factor agents (P = .051), the reutilization group demonstrated longer recurrence-free survival. CONCLUSIONS:Reutilization of biologic classes can be a valid strategy to prevent postoperative CD recurrence.

Fecal microbiota-based therapies are safe and effective in preventing recurrent Clostridioides difficile infection (rCDI) after standard of care (SOC) antibiotic treatment with either vancomycin or fidaxomicin.^1,2 Prior studies of United States Food and Drug Administration (FDA)-unapproved, full-spectrum fecal microbiota transplant (FMT) following SOC antibiotic therapy have been shown to prevent rCDI through restoration of the gut microbiota by infusion of healthy donor stool. In November of 2022 and April of 2023, the FDA approved fecal microbiota, live-jslm (RBL), and fecal microbiota spores, live-brpk (VOS), to prevent rCDI by targeting dysbiosis and restoring the gut microbiome following SOC antibiotic therapy in those at greatest risk for future recurrence.^3,4 The efficacy of these novel microbiota-based live biotherapeutics in a real-world cohort and compared with conventional FMT remains unknown. Thus, we aimed to analyze the efficacy and safety of RBL and VOS in a real-world multicenter patient population and compare this with FDA-unapproved FMT.

BACKGROUND:Although pouchitis is the most common complication after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC), the influence of diet on pouchitis is poorly understood. Thus, evidence-based dietary recommendations after IPAA are limited. AIMS/OBJECTIVE:We evaluated dietary intake in the period after the final stage of IPAA for UC and Body Mass Index (BMI) to identify potential associations with pouchitis. METHODS:We used the Dietary Screener Questionnaire (DSQ) to assess dietary intake among patients in a prospective cohort enrolled within 2 weeks of the final stage of IPAA for UC. We compared food group and fiber intake of those who developed pouchitis within 12 months of the final stage of IPAA with those who did not. These were also compared to the United States Department of Agriculture (USDA) recommended daily goals. RESULTS:Among 89 patients, there was no significant difference in individual fiber intake when comparing those who developed pouchitis and those who did not. In comparison with USDA guidelines, both groups (pouchitis and no pouchitis) exhibited decreased intake of several food groups, such as fruits, vegetables, fiber, and dairy. Patients who developed pouchitis had a significantly higher median body mass index (BMI) at the time of surgery compared to patients who did not develop pouchitis (median 29.2 vs. 24.8, P = 0.022). CONCLUSIONS:In a prospective cohort, we identified no association between dietary intake and development of pouchitis within the first year after IPAA. However, elevated BMI may represent a unique target for intervention to prevent pouchitis occurrence.

BACKGROUND:Lynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and results from pathogenic germline variants affecting mismatch repair. The tissue microenvironment that contributes to this elevated risk of CRC is poorly characterised particularly during the early precancerous stages. OBJECTIVE:To define features of the colonic microenvironment that distinguish LS carriers with and without a history of CRC from one another and from the general population. DESIGN/METHODS:We applied Expanded Cellular Indexing of Transcriptomes and Epitopes by sequencing, a multimodal single-cell platform, to profile tumour-free colonic cellular composition and transcriptome of LS carriers with and without a history of CRC compared with general population controls. We used flow cytometry, histology and mouse modelling to validate key observations. RESULTS:expression in epithelial progenitors, validated by orthogonal techniques including demonstration of a protective function in a murine model of CRC. CONCLUSIONS:These findings define key features of the LS colonic microenvironment and suggest that MAIT cell enrichment contributes to immune surveillance against CRC, offering new insights into disease penetrance, risk stratification and prevention.

BACKGROUND:Chronic intestinal inflammation is a well-established driver of colorectal dysplasia in inflammatory bowel disease (IBD). However, the role of metabolic factors such as obesity remains poorly understood. We evaluated whether chronic obesity, measured using five-year longitudinal body mass index (BMI), is independently associated with colorectal dysplasia in patients with IBD. METHODS:using all outpatient measurements over a five-year period prior to the index colonoscopy. Multivariable conditional logistic regression was used to evaluate the association between obesity and dysplasia, adjusting for established dysplasia risk factors and surveillance-related variables. RESULTS:A total of 312 patients were included (156 dysplasia cases and 156 matched controls). Dysplasia cases had significantly longer IBD duration compared with controls (median 12.1 vs. 8.0 years, p < 0.01) and were more likely to have a history of prior colorectal dysplasia (16.0% vs. 3.8%, p < 0.01). In multivariable analysis, obesity was independently associated with colorectal dysplasia (adjusted odds ratio [aOR] 2.23, 95% CI 1.08-4.57). Longer disease duration (aOR 1.05 per year, 95% CI 1.02-1.08) and prior dysplasia (aOR 4.88, 95% CI 1.69-14.06) were also independently associated with dysplasia. In a secondary model adjusting for additional surveillance-related and structural colonic factors, obesity remained significantly associated with dysplasia (aOR 2.11, 95% CI 1.05-4.24). CONCLUSIONS:Obesity is independently associated with colorectal dysplasia in patients with IBD, suggesting that metabolic factors contribute to neoplastic risk beyond traditional inflammation-driven pathways. Incorporation of metabolic risk into dysplasia risk stratification may improve CRC prevention strategies in IBD.