This comprehensive review explores the increasing prevalence of obesity among inflammatory bowel disease (IBD) patients and investigates its impact on disease pathophysiology, response to therapy, and overall clinical outcomes. As obesity rates rise globally, it is important to recognize the complex interplay between obesity and IBD. Contrary to the misconception that IBD patients are predominantly underweight, current evidence suggests that 15–40

Increasing evidence has linked obesity to complications of inflammatory bowel disease (IBD); however, data are limited on the efficacy and impact of weight management strategies on the disease course. There are a strikingly limited number of interventional studies on weight management in patients with IBD, and the recent nutrition and IBD guidelines published in the United States do not mention weight management strategies. Overweight and obesity management in patients with IBD should follow a stepwise approach to assessment and treatment, including lifestyle modification, anti-obesity medications such as glucagon-like peptide-1 agonists, endobariatric procedures, and bariatric surgery (if deemed appropriate). This article reviews the management of overweight and obesity in patients with IBD, examines the efficacy of currently available interventions and their impact on the IBD course, and proposes a stepwise approach to the assessment and treatment of overweight or obesity for the IBD provider.

Vaccines against SARS-CoV-2 are important for protection from COVID-19; however, patients with immune-mediated conditions and patients taking immunosuppressive medications, including patients with inflammatory bowel disease (IBD), were excluded from studies demonstrating the safety and efficacy of these vaccines. This article provides an overview of the research and recommendations currently published on vaccines against COVID-19 in adult populations with IBD, including studies evaluating effects of commonly used medications. COVID-19 vaccines are strongly recommended for patients with IBD. Messenger RNA (mRNA) and adenovirus vector vaccines are safe in patients with IBD, and reports of severe reactions or IBD flares are rare. Studies assessing antibody response, T-cell immunity, and real-world experience demonstrate positive outcomes for mRNA and adenovirus vector vaccines in patients with IBD, although mRNA vaccines may have a slight advantage. Studies assessing inactive COVID-19 vaccines are still needed. Immunosuppressive therapies used in IBD, especially tumor necrosis factor antagonists, combination therapy, and corticosteroids, may reduce antibody responses and durability, but the impact on infection, hospitalizations, and death requires further evaluation. Educating patients with this evidence-based information will likely help to reduce concerns and vaccine hesitancy.

BACKGROUND There are limited data on coronavirus disease 2019 (COVID-19) in vaccinated patients with inflammatory bowel disease (IBD). We aimed to describe outcomes and identify risk factors for hospitalization, severe COVID-19, and death in this population. METHODS Data from the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database were analyzed. Patients with IBD who received at least one vaccine dose prior to diagnosis of COVID-19 were included. Patients received mRNA (Pfizer and Moderna), adenovirus vector (CanSino, AstraZeneca, Sputnik, and Janssen), or inactivated SARS-CoV-2 (Sinovac) vaccines. Partial vaccination was defined as having not received the full complement of doses for the vaccine received. Outcomes were hospitalization, death, and severe COVID-19, a composite of intensive care unit admission, mechanical ventilation, and/or death. RESULTS Among 141 cases, 12 (8.5%) were hospitalized, 4 (2.8%) had severe COVID-19, and 1 (0.7%) died. During the same period, proportions in the unvaccinated were 9.3%, 1.9%, and 1.2%, respectively. Nearly three-quarters of patients with COVID-19 after vaccination were on biologics and one-third were taking immunomodulators. Fewer hospitalizations occurred in those with completed vaccine series than partially complete series (5.7% vs 13.2%, p = 0.13), and in those receiving mRNA vaccines than adenovirus vector (4.7% vs 22.7%, p = 0.01) or inactivated SARS-CoV-2 (4.7% vs 16.7%, p=0.15) vaccines. Only 2.9% of those with completed mRNA series were hospitalized. Patients on biologic monotherapy were less frequently hospitalized than patients on immunomodulator monotherapy (4.2% vs 27.3%, p=0.03) or combination therapy (4.2% vs 10.0%, p = 0.36). Overall, hospitalized patients were older (mean age 50 years vs 40 years, p = 0.03). Severe COVID-19 was less common in those receiving mRNA vaccines than adenovirus vector (0.9% vs 4.6%; p = 0.31) or inactivated SARS-CoV-2 (0.9% vs 16.7%; p = 0.02) vaccines. Of the four patients with severe COVID-19, two were taking tumor necrosis factor antagonists, three were taking azathioprine, and one had chronic lung disease. The only death was in a patient on triple immunosuppression with adalimumab, azathioprine, and systemic steroids. CONCLUSION In patients with IBD, incomplete vaccination, non-mRNA vaccines, and immunomodulator use are associated with increased risk of adverse events during COVID-19 infections.

Background Coronavirus disease 2019 (COVID-19) can increase the risk of thrombosis, cardiovascular events, and kidney injury, but risks among patients with inflammatory bowel disease (IBD) remain unknown.We aimed to characterize risk for these complications among patients with IBD who developed COVID-19.Methods We analyzed complications of COVID-19 in patients reported to the Surveillance Epidemiology of Coronavirus Under Research Exclusion in Inflammatory Bowel Disease (SECURE-IBD) database prior to November 15, 2021.Our primary outcome was a composite of thrombotic complications (peripheral venous thrombosis, pulmonary embolism, thrombotic stroke, and peripheral arterial thrombosis), cardiovascular complications (new arrhythmia, heart failure, myocarditis/pericarditis, and vasculitis), and renal complications (acute kidney injury).Covariates included cardiovascular disease (including stroke), cardiovascular risk factors (diabetes mellitus, hypertension, or smoking), pulmonary disease (asthma, chronic obstructive pulmonary disease, or other chronic lung disease), thrombotic risk conditions (cancer), chronic kidney disease, chronic liver disease, "other" comorbidities, and COVID-19 vaccination with at least one dose.Multivariable analyses assessed the independent effect of variables significant in univariate analyses.Results Among 4,923 patients reported to SECURE-IBD, 79 (1.6%) had thrombotic, cardiovascular, and/or renal complications.There were 45 (0.9%) reports of acute kidney injury, 24 (0.5%) of arrythmias, 8 (0.2%) of peripheral venous thrombosis, 5 (0.1%) each of heart failure, myocarditis/pericarditis, and pulmonary embolism, and 1 (0.02%) each of vasculitis, peripheral atrial thrombosis, and thrombotic stroke.In univariate analyses, complications were more common in patients who were older (p < 0.01), black (p < 0.01), and on corticosteroids (p < 0.01) (Table 1).Patients with severe IBD were more likely to have complications than patients in remission (p < 0.01), as were those with more comorbidities (p < 0.01).Cardiovascular disease, cardiovascular risk factors, pulmonary disease, and chronic renal disease were associated with increased risk (p < 0.01 each).There was no association with vaccination status (p = 1).In multivariate analyses, age (aOR 1.04 [1.03, S-599 AGA Abstracts1.06]), black race (aOR 4.02 [1.53, 10.55]), severe IBD (aOR 3.21 [1.31, 7.86]), corticosteroid use (aOR 3.63 [1.85, 7.12]), and one (aOR 2.33 [1.10, 4.91]), two (aOR 4.24 [1.42, 12.65]), and three or more (aOR 13.36 [3.48, 51.32]) comorbidities were significant predictors of complications (Table 2).Discussion Thrombotic, cardiovascular, and renal complications from COVID-19 were uncommon among patients with IBD.Patients with older age, black race, corticosteroid use, severe IBD, and greater number of comorbidities may require closer monitoring if they develop COVID-19.Su1494

Abstract Background Preliminary evidence suggests changes in breast milk cytokines in women with inflammatory bowel disease (IBD) compared to healthy controls, with potential implications toward offspring immunological development. However, changes in breast milk cytokine profiles in consecutive pregnancies are not known. Methods In this pilot study, we prospectively enrolled 11 pregnant women with, and 10 without IBD during two consecutive pregnancies and collected clinical data during each pregnancy and post birth. We collected breast milk samples at two weeks post birth and obtained the expression levels of 92 cytokines using the Olink proteomic platform. We further analyzed the correlation of cytokine profiles within each sample, in paired breast milk samples from consecutive pregnancies, and in random two unpaired breast milk samples, of women with and without IBD. Results The baseline characteristics of women with and without IBD were comparable (Table). The cytokine profiles were significantly correlated between paired breast milk samples from consecutive pregnancies compared to unpaired breast milk samples from women with or without IBD. The overall correlations of cytokine profiles in paired IBD pregnancies were significantly higher than the controls (Figure). Conclusion Our pilot study results suggest that the breast milk cytokine signatures are more conserved in consecutive pregnancies of women with IBD compared to those without IBD. Future analysis will test if our findings have implications toward familial clustering of immune functions in offspring.

Abstract Background There are increasing data on changes in intestinal inflammation and microbiome diversity during pregnancy in women with inflammatory bowel disease (IBD) with implications towards individual and offspring immune function. However, differences in intestinal inflammation, as measured by fecal calprotectin (FC) and microbial a-diversity, in consecutive pregnancies are not known. Methods We prospectively enrolled a cohort of women, 37 with IBD and 39 without IBD, during two consecutive pregnancies, and their offspring. We collected serial stool samples and clinical data, and measured FC and bacterial abundance during each trimester of each pregnancy. We further performed correlation analysis between FC in consecutive pregnancies and between microbial a-diversity in consecutive pregnancies among women with and without IBD. Results Compared to healthy controls, IBD pregnancies had significantly lower gestational age at birth and higher frequency of Cesarean section. Mode of delivery, the status of Group B Streptococcus (GBS) infection and GBS infection prophylaxis were significantly associated with the pregnancy order in both IBD and controls (Table). Furthermore, we observed strong correlations of FC (r=0.56, p-value=0.093) and microbial alpha-diversity assessed as operational taxonomic unit (OTU) richness (r=0.88, p=0.0087) between paired consecutive pregnancies in women with IBD, but not in those without IBD (Figure). There were no differences in microbial alpha-diversity using the Shannon and Simpson indices when comparing consecutive pregnancies of women with and without IBD. Conclusion In this study, we demonstrate that intestinal inflammation and microbiome diversity are more conserved in consecutive pregnancies of women with IBD compared to healthy controls. These findings may have implications towards understanding the impact of pregnancy on host-microbiome interactions in IBD as well as the potential impact on offspring health.

Histologic healing is emerging as a goal in ulcerative colitis, and the FDA will now require it for a claim of “mucosal healing.” However, issues identified in this editorial, including definitions, protocols, and clinical relevance, will need to be addressed.

OBJECTIVE:This study evaluated the association between exposure to several chemicals and mortality from lymphohematopoietic cancer (LHC) among 16,579 synthetic rubber industry workers who were followed up from 1943 to 1998. METHODS:Poisson regression analyses examined LHC rates in relation to butadiene, styrene, and DMDTC exposure. Models provided maximum likelihood estimates of the relative rate for the contrast between categories of one agent, adjusting for other agents and for additional potential confounders. RESULTS:Cumulative exposure to 1,3-butadiene was associated positively with all leukemia (relative rates of 1.0, 1.4, 1.2, 2.9, and 3.7, respectively, for exposures of 0, >0 to <33.7, 33.7 to <184.7, 184.7 to <425.0, and 425.0+ ppm-years), chronic myelogenous leukemia and to a lesser extent with chronic lymphocytic leukemia. Adjusting for styrene and DMDTC attenuated these associations. After controlling for butadiene, neither styrene nor DMDTC displayed a consistent exposure-response trend with all leukemia, chronic myelogenous leukemia, or chronic lymphocytic leukemia. CONCLUSIONS:This study found a positive association between butadiene and leukemia that was not explained by exposure to other agents examined.

Patients with inflammatory bowel diseases [IBD] are frequently treated with immunosuppressant medications. During the coronavirus disease 2019 [COVID-19] pandemic, recommendations for IBD management have included that patients should stay on their immunosuppressant medications if they are not infected with the severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2], but to temporarily hold these medications if symptomatic with COVID-19 or asymptomatic but have tested positive for SARS-CoV-2. As more IBD patients are infected globally, it is important to also understand how to manage IBD medications during convalescence while an individual with IBD is recovering from COVID-19. In this review, we address the differences between a test-based versus a symptoms-based strategy as related to COVID-19, and offer recommendations on when it is appropriate to consider restarting IBD therapy in patients testing positive for SARS-CoV-2 or with clinical symptoms consistent with COVID-19. In general, we recommend a symptoms-based approach, due to the current lack of confidence in the accuracy of available testing and the clinical significance of prolonged detection of virus via molecular testing.

Background and aimsPrenatal and early life bacterial colonisation is thought to play a major role in shaping the immune system. Furthermore, accumulating evidence links early life exposures to the risk of developing IBD later in life. We aimed to assess the effect of maternal IBD on the composition of the microbiome during pregnancy and on the offspring’s microbiome.MethodsWe prospectively examined the diversity and taxonomy of the microbiome of pregnant women with and without IBD and their babies at multiple time points. We evaluated the role of maternal IBD diagnosis, the mode of delivery, antibiotic use and feeding behaviour on the microbiome composition during early life. To assess the effects of IBD-associated maternal and infant microbiota on the enteric immune system, we inoculated germ-free mice (GFM) with the respective stool and profiled adaptive and innate immune cell populations in the murine intestines.ResultsPregnant women with IBD and their offspring presented with lower bacterial diversity and altered bacterial composition compared with control women and their babies. Maternal IBD was the main predictor of the microbiota diversity in the infant gut at 7, 14, 30, 60 and 90 days of life. Babies born to mothers with IBD demonstrated enrichment in Gammaproteobacteria and depletion in Bifidobacteria. Finally, GFM inoculated with third trimester IBD mother and 90-day infant stools showed significantly reduced microbial diversity and fewer class-switched memory B cells and regulatory T cells in the colon.ConclusionAberrant gut microbiota composition persists during pregnancy with IBD and alters the bacterial diversity and abundance in the infant stool. The dysbiotic microbiota triggered abnormal imprinting of the intestinal immune system in GFM.

sleeping divided by time in bed.The average of up to seven days of data was then calculated."Clinically active" was defined as Harvey-Bradshaw Index of > 4 for CD or Simple Clinical Colitis Activity Index of $ 1 for UC.Each parameter was compared between disease states, then logistic regression for the outcome of clinically active disease.Multivariate analysis included age, sex, diagnosis, and comorbid sleep disorder with each sleep parameter.Results: 38 patients (26 CD, 12 UC) were followed for an average of 8.87 nights.There were no significant differences between CD and UC for age, male sex, or clinically active disease, though there was a difference in the presence of comorbid sleep disorders (table 1).A change in average sleep fragmentation by 0.1 was not predictive of clinically active disease in the univariate model, but was predictive in the multivariate model (OR 1.78 (95% CI 1.004 -3.11), p = 0.02) (table 2).While restlessness (OR 1.14 (95% CI 0.34 -3.82), p = 0.82) and sleep efficiency (OR 0.019 (95% CI 8x10-5 -4.41), p = 0.14) were not predictive.Conclusions: Worse sleep fragmentation measured by a wearable activity tracking device is associated with increased odds of clinical disease activity in IBD.Changes in sleep fragmentation patterns may have utility in a remote patient monitoring system as an early indicator of clinical disease activity.

The Spanish IBD Registry (ENEIDA) is reporting in this issue of the Journal on a retrospective assessment of outcomes of cyclosporine use and infliximab use to treat steroid refractory acute severe ulcerative colitis (SR-ASUC) between 1989 and 2013. Overall, they found similar outcomes in terms of 3 month and 1 year colectomy rates. Serious adverse events were lower in cyclosporine users. While this study does not meet the standard of a prospective randomized controlled trial, it does remind us that cyclosporine can be effective in (SR-ASUC) and should be considered in those who have already failed antibody to tumor necrosis factor therapy or as a bridge to immunomodulators that have a slower onset of action.

Background: Human studies have demonstrated changes in the diversity and abundance of the microbiome during pregnancy coinciding with changes in maternal immune status. Furthermore, accumulating evidence suggests that maternal health may influence the newborn's microbiome development. These balancing acts may be even more complicated in pregnant women with IBD, who exhibit a variety of immunological and gut microbiota alterations. Yet, no data exist on the effect of IBD on the microbiome during pregnancy, and its role on the infant gut microbiota composition. Methods: The “Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome” (MECONIUM) Study is a prospective study that recruits pregnant women with and without IBD and their offspring. Stool and saliva samples were collected during pregnancy, and placenta was collected at delivery. Serial stool samples were collected from the newborns up to 90 days of life. The microbial composition was surveyed using 16S rRNA sequencing. QIIME was used to compare the overall microbiota diversity, and the LEfSe method was used to find differential taxa features. Results: 125 pregnant women (43 with IBD) and 79 babies (26 born to mothers with IBD) were included; 193 maternal samples (148 stool, 45 placenta) and 245 infant stool samples were analyzed. Among all babies, 35.4% were born via C-section and 96% were full-term. Even though 74% of women with IBD were in remission throughout pregnancy, this group presented lower bacterial diversity (p=0.001, ANOVA), and different overall bacterial composition in stool (p=0.001; PERMANOVA, unweighted Unifrac), with enrichment in Gammaproteobacteria and a decrease in Bacteroidetes. Mothers with IBD presented differences in the overall composition of their placental microbiome (p=0.001) with a decrease in Firmicutes, and expansion in Alphaproteobacteria and Actinobacteria. Babies born to IBD mothers showed a different stool bacterial composition (p=0.001), that persisted over time, with expansion of Gammaproteobacteria and a reduction in Actinobacteria taxa, differences that were independent of mode of delivery (Figure). Figure. Results from LefSe analysis in mothers and their infants. Conclusions: IBD women maintain dysbiosis in their gut microbiota during pregnancy, and present with different placental microbiome. Babies born to mothers with IBD demonstrate different gut microbiome composition that persists for up to 3 months of life, and is independent of mode of delivery. These findings suggest that maternal IBD status affects the gut microbiome composition in offspring, which could contribute to future disease risk.