Onset Inflammatory Bowel Disease Research Articles

Inflammatory Bowel Disease: The Emergence of New Trends in Lifestyle and Nanomedicine as the Modern Tool for Pharmacotherapy.

The human intestine, which harbors trillions of symbiotic microorganisms, may enter into dysbiosis when exposed to a genetic defect or environmental stress. The naissance of chronic inflammation due to the battle of the immune system with the trespassing gut bacteria leads to the rise of inflammatory bowel disease (IBD). Though the genes behind the scenes and their link to the disease are still unclear, the onset of IBD occurs in young adults and has expanded from the Western world into the newly industrialized countries. Conventional drug deliveries depend on a daily heavy dosage of immune suppressants or anti-inflammatory drugs targeted for the treatment of two types of IBD, ulcerative colitis (UC) and Crohn’s disease (CD), which are often associated with systemic side effects and adverse toxicities. Advances in oral delivery through nanotechnology seek remedies to overcome the drawbacks of these conventional drug delivery systems through improved drug encapsulation and targeted delivery. In this review, we discuss the association of genetic factors, the immune system, the gut microbiome, and environmental factors like diet in the pathogenesis of IBD. We also review the various physiological concerns required for oral delivery to the gastrointestinal tract (GIT) and new strategies in nanotechnology-derived, colon-targeting drug delivery systems.

15308 Frequency of gastrointestinal-related serious adverse events among guselkumab-treated patients with moderate to severe psoriasis: A pooled analysis of Voyage 1 and Voyage 2 through 3 years

Background and Objective: Some biologics used to treat psoriasis are associated with exacerbation or new onset of inflammatory bowel disease (IBD). Long-term safety data through 3 years of continuous guselkumab (GUS) treatment from pivotal phase 3 clinical trials in moderate to severe psoriasis were analyzed for the incidence of GI-related serious adverse events (SAEs).

Very early onset inflammatory bowel disease in a South Asian country where inflammatory bowel disease is emerging: a distinct clinical phenotype from later onset disease.

Background/AimsInformation on pediatric inflammatory bowel disease (PIBD) and very early onset IBD (VEOIBD) are sparse in India, where IBD is emerging. We aimed to evaluate characteristics of VEOIBD and later onset PIBD (LO-PIBD) in India.MethodsWe performed retrospective analysis of a large, prospectively maintained IBD registry. PIBD was divided in to VEOIBD (< 6 years) and LO-PIBD (6–17 years). Demographic data, disease characteristics and treatment were compared between the PIBD groups and with other Asian/Western studies as well as the adult patients of the registry.ResultsOf 3,752 IBD patients, 292 (7.8%) had PIBD (0–17 years) (175 Crohn’s disease [CD], 113 ulcerative colitis [UC], 4 IBD-undifferentiated; 22 VEOIBD [7.5%], and 270 LO-PIBD [92.5%]). VEOIBD patients had more severe disease compared to LO-PIBD in both UC (P=0.003) and CD (P<0.001). Familial IBD was more common in VEOIBD (13.6%) compared to LO-PIBD (9.2%). Ileal disease (L1) was an independent risk factor for diagnostic delay in pediatric CD. Diagnostic delay (> 6 months) was significantly lower in VEOIBD (40.9%) than in LO-PIBD (78.8%) (P<0.001). Compared to other Asian and Western studies, extensive UC (72.5%) and complicated CD (stricturing/penetrating: 42.7%) were relatively more common. Perianal CD was relatively less frequent (7.4%). PIBD had a significantly higher number of complicated and ileal CD and extensive UC comparison to adult cohort of the registry.ConclusionsVEOIBD has more aggressive phenotype than LO-PIBD. Disease appears distinct from other Asian and Western studies and adult onset disease, with more complicated CD and extensive UC.

Clinical characteristics and validation of diagnosis in individuals with Hirschsprung disease and inflammatory bowel disease

Background/purposeHirschsprung disease has previously been reported to be associated with inflammatory bowel disease (IBD). The aim was to clinically confirm the diagnosis and to describe characteristics among individuals with both conditions in a national populationbased cohort. MethodsNationwide, population-based cohort study, including all individuals with a Hirschsprung disease diagnosis and an IBD diagnosis registered between 1964 and 2016, in which clinical data were collected from the medical records of 18 validated cases with both Hirschsprung disease and IBD. The medical record of each individual in the study cohort was reviewed for age at IBD diagnosis, type of aganglionosis, type of surgical treatment, subtype of IBD, and treatment for IBD. ResultsMedian age at follow up was 34 years (range 19–66), and 3 of 18 indivduals (17%) were females. Median age at first diagnosis of IBD was 21 years (range 10–46). Six patients had ulcerative colitis, ten had Crohn's disease and two had unclassified IBD. Most of the patients had pharmacological treatment for IBD and 5 (28%) individuals had surgical treatment. ConclusionHirschsprung disease and IBD was clinically confirmed in 18 cases. Age at IBD onset and subtype of IBD is similar to IBD patients without Hirschsprung disease. Five individuals had undergone surgical treatment for IBD.

The E3 ubiquitin ligase UBR5 interacts with TTC7A and may be associated with very early onset inflammatory bowel disease

Very early onset inflammatory bowel disease (VEOIBD) denotes children with onset of IBD before six years of age. A number of monogenic disorders are associated with VEOIBD including tetratricopeptide repeat domain 7A (TTC7A) deficiency. TTC7A-deficiency is characterized by apoptotic colitis in milder cases with severe intestinal atresia and immunodeficiency in cases with complete loss of protein. We used whole exome sequencing in a VEOIBD patient presenting with colitis characterized by colonic apoptosis and no identified known VEOIBD variants, to identify compound heterozygous deleterious variants in the Ubiquitin protein ligase E3 component N-recognin 5 (UBR5) gene. Functional studies demonstrated that UBR5 co-immunoprecipitates with the TTC7A and the UBR5 variants had reduced interaction between UBR5 and TTC7A. Together this implicates UBR5 in regulating TTC7A signaling in VEOIBD patients with apoptotic colitis.

Raman Spectroscopy as Noninvasive Method of Diagnosis of Pediatric Onset Inflammatory Bowel Disease

We propose here a spectroscopic method to diagnose and differentiate inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD) with pediatric onset, in a complete noninvasive way without performing any duodenal biopsy. In particular, the Raman technique was applied to proteic extract from fecal samples in order to achieve information about molecular vibrations that can potentially furnish spectral signatures of cellular modifications occurring as a consequence of specific pathologic conditions. The attention was focused on the investigation of the amide I region, quantitatively accounting the spectral changes in the secondary structures by applying deconvolution and curve-fitting. Inflammation is found to give rise to a significant increasing of the nonreducible (trivalent)/reducible (divalent) cross-linking ratio R of the protein network. This parameter revealed an excellent marker in order to distinguish IBD subjects from non-IBD ones, and, among IBD patients, to differentiate between UC and CD. The proposed methodology was validated by statistical analysis using the receiver operating characteristic (ROC) curve.

S0724 Characteristics of Crohn's Disease Patients in the Corrona Inflammatory Bowel Disease Registry on Biological or Conventional Therapy Differ by Disease Duration

INTRODUCTION: Real-world comparisons of Crohn's Disease (CD) patients on biologic (BIO) vs conventional (CONV) therapy may be confounded by differences in patient characteristics, including duration of disease. This study aimed to characterize CD patients by therapy group and disease duration. METHODS: CD patients in the Corrona Inflammatory Bowel Disease (IBD) Registry from 5/3/17 to 3/3/20 were grouped by therapy at enrollment as BIO or biologic-naïve CONV (5-ASAs or immunosuppressants) and by short disease duration (ShD) <10 years or long duration (LD) ≥10 years. Patient characteristics, including patient-reported outcomes (PROs), were compared using standardized differences (Sdiff), where >0.10 represents a relevant imbalance between groups. RESULTS: Among 774 CD patients in the study, both ShD (n = 372) and LD (n = 402), a higher % of patients on BIO were younger, male, had private insurance (Table 1), history of ER use for IBD, ileal and less colonic disease, and younger age of IBD onset than CONV (Table 2). Compared to CONV-ShD, BIO-ShD had shorter time since CD symptom onset but longer time since CD diagnosis, similar mean Harvey-Bradshaw Index (HBI), % in remission, and current perianal fistula, but more previous perianal fistula, penetrating and stricturing disease, history of IBD surgery, and >1 surgery type (Table 2). BIO-ShD had less fatigue, pain interference, depression, and anxiety (Patient-Reported Outcomes Measurement Information System (PROMIS)), and less absenteeism, presenteeism, and % work and daily activities affected by IBD (Work Productivity Activity Impairment (WPAI)) (Table 3). Compared to CONV-LD, BIO-LD had shorter time since CD symptom onset and diagnosis, similar mean HBI and % in remission, but more stricturing disease, current, and prior perianal fistulas, history of IBD surgery, >1 surgery type, and ER use for IBD (Table 2). BIO-LD had more fatigue, sleep disturbance, pain interference, depression, and anxiety (PROMIS), and more absenteeism, presenteeism, and % work and daily activities affected by IBD (WPAI) (Table 3). CONCLUSION: Despite similar HBI and % in remission, BIO-LD had worse PROs, more structural damage, and prior treatment than CONV-LD. BIO-ShD had better PROs despite similar or worse disease characteristics than CONV-SD. These results suggest that HBI does not capture the full burden of CD, and biologic therapies may be associated with better PROs when started earlier in the disease process before structural damage occurs.Table 1.: Patient demographics and comorbidities, overall and by biologic therapy vs. conventional (biologic naïve) therapy for patients with Crohn's Disease (CD) with disease duration <10 years vs. ≥10 yearsTable 2.: Patient disease and treatment characteristics overall and by biologic therapy vs. conventional (biologic naïve) therapy for patients with Crohn's Disease (CD) with disease duration <10 years vs. ≥10 yearsTable 3.: Patient reported outcomes (PROs) overall and by biologic therapy vs. conventional (biologic naïve) therapy for patients with Crohn's Disease (CD) with disease duration <10 years vs. ≥10 years

Population-Based Evidence From a Western Canadian Province of the Decreasing Incidence Rates and Trends of Inflammatory Bowel Disease Among Adults.

Background and AimsCanada has one of the highest inflammatory bowel disease (IBD) incidence rates worldwide. Higher IBD incidence rates have been identified among urban regions compared to rural regions. The study objectives were to (i) estimate IBD incidence rates in Saskatchewan from 1999 to 2016 and (ii) test for differences in IBD incidence rates for rural and urban regions of Saskatchewan.MethodsA population-based study was conducted using provincial administrative health databases. Individuals aged 18+ years with newly diagnosed Crohn’s disease or ulcerative colitis were identified using a validated case definition. Generalized linear models with a negative binomial distribution were used to estimate incidence rates and incidence rate ratios (IRRs) adjusted for age group, sex and rurality with 95% confidence intervals (CIs).ResultsThe average annual incidence rate of IBD among adults in Saskatchewan decreased from 75/100,000 (95% CI 67 to 84) in 1999 to 15/100,000 (95% CI 12 to 18) population in 2016. The average annual incidence of IBD declined significantly by 6.9% (95% CI −7.6 to −6.2) per year. Urban residents had a greater overall risk of IBD (IRR = 1.19, 95% CI 1.11 to 1.27) than rural residents. This risk difference was statistically significant for Crohn’s disease (IRR = 1.25, 95% CI 1.14 to 1.36), but not for ulcerative colitis (IRR = 1.08, 95% CI 0.97 to 1.19).ConclusionsThe incidence of IBD in Saskatchewan dropped significantly from 1999 to 2016 with urban dwellers having a 19% higher risk of IBD onset compared to their rural counterparts. Health care providers and decision-makers should plan IBD-specific health care programs considering these specific IBD rates.

Integrated strategy based on microecological therapy in the treatment of inflammatory bowel disease

Inflammatory bowel disease (IBD) is a group of chronic, recurrent, and inflammatory intestinal diseases. At present, it is believed that the destruction of intestinal homeostasis may be the cause of the onset and progression of IBD. Under normal circumstances, the maintenance of intestinal homeostasis depends on the balance among the intestinal microbes, the intestinal mucosal barrier, and the immune system. Accordingly, the treatment strategy for IBD must take into account micro-ecological reconstruction, immune regulation and intestinal barrier function recovery. Because different patients have different responses to incentives, different treatments, or those at different stages of the disease course show different disease behaviors, multidisciplinary collaboration seems quite necessary. This article aims to introduce a five-in-one integrated treatment strategy, including microecological treatment, immunotherapy, enteral nutrition, interventional therapy, and surgical treatment.

Children\u2019s rare disease cohorts: an integrative research and clinical genomics initiative

While genomic data is frequently collected under distinct research protocols and disparate clinical and research regimes, there is a benefit in streamlining sequencing strategies to create harmonized databases, particularly in the area of pediatric rare disease. Research hospitals seeking to implement unified genomics workflows for research and clinical practice face numerous challenges, as they need to address the unique requirements and goals of the distinct environments and many stakeholders, including clinicians, researchers and sequencing providers. Here, we present outcomes of the first phase of the Children’s Rare Disease Cohorts initiative (CRDC) that was completed at Boston Children’s Hospital (BCH). We have developed a broadly sharable database of 2441 exomes from 15 pediatric rare disease cohorts, with major contributions from early onset epilepsy and early onset inflammatory bowel disease. All sequencing data is integrated and combined with phenotypic and research data in a genomics learning system (GLS). Phenotypes were both manually annotated and pulled automatically from patient medical records. Deployment of a genomically-ordered relational database allowed us to provide a modular and robust platform for centralized storage and analysis of research and clinical data, currently totaling 8516 exomes and 112 genomes. The GLS integrates analytical systems, including machine learning algorithms for automated variant classification and prioritization, as well as phenotype extraction via natural language processing (NLP) of clinical notes. This GLS is extensible to additional analytic systems and growing research and clinical collections of genomic and other types of data.

The food contaminant, deoxynivalenol, modulates the Thelper/Treg balance and increases inflammatory bowel diseases.

The incidence of inflammatory bowel diseases (IBD) is increasing in both Western and developing countries. IBD are multifactorial disorders involving complex interactions between genetic, immune, and environmental factors such as exposure to food contaminants. Deoxynivalenol (DON) is the most prevalent mycotoxin that contaminates staple food and induces intestinal breakdown and inflammatory response. To delineate the role of DON oral exposure in IBD, we used a Dextran sulfate sodium (DSS) colitis model in rats fed with a DON-contaminated diet or a control diet for 4weeks. Colitis was induced in the 4thweek by increasing concentrations of DSS in the drinking water (0, 2, 3 or 5%). DON exacerbated body weight loss and accelerated the appearance of symptoms in animals treated with DSS. DON increased morphological damage, pro-inflammatory markers (myeloperoxidase, CXCL-1 and IL-1β) and immune cell responses. In lamina propria of the rat with colitis, DON increased adaptive and innate immune responses after anti-CD3/28 or LPS stimulation, respectively. In the spleen, DON increased IFNγ secretion and reduced Treg populations. Interestingly, De-epoxy-DON (DOM-1) a detoxified form of DON did not have any consequences on colitis. These results suggest that DON is a risk factor in the onset of IBD.

Analysis of clinical characteristics and drug treatment of inflammatory bowel disease in children: a single center study

Objective: To analyze the clinical characteristics and efficacy of drug treatment in children with inflammatory bowel disease (IBD) at different ages of onset. Methods: The clinical data of 87 children with IBD admitted to Department of Gastroenterology in Children's Hospital, Capital Institute of Pediatrics from January 2009 to December 2018 were collected. The patients were divided into four groups according to the age of onset: 0 -<2 years old group (36 cases), 2 -<6 years old group (10 cases), 6 -<10 years old group (12 cases) and 10 -<18 years old group (29 cases). The clinical manifestations, laboratory examination, endoscopic findings, pathologic and genetic changes, and treatment were compared among different age groups with chi-square test or Fisher's exact text. Results: (1) A total of 87 patients were diagnosed with IBD, including 50 Crohn's disease (CD) (57%), 25 ulcerative colitis (UC) (29%) and 12 unclassified inflammatory bowel disease (IBD-U) (14%). (2) Patients with fever accounted for 78% (28/36) and 8/10 in the 0 -<2 years old group and 2 -<6 years old group, respectively. Patients with abdominal pain and perianal diseases accounted for 6% (2/36) and 47% (17/36) in the 0 -<2 years old group, and their proportions were significantly different among the four groups (χ(2)=8.369, 40.317 and 13.130, all P<0.05). (3) Leukocytosis, thrombocytosis and anemia were more common in the 0-<2 years old group, seen in 72% (26/36), 31% (11/36) and 81% (29/36), respectively. There were significant differences in the changes of complete blood count among the four groups (χ(2)=21.919, 8.095 and 11.520, all P<0.05). (4) Colonic involvement accounted for 85% (17/20) in the 0 -<2 years old CD patients. While in the CD patients over 6 years old, 61% (14/23) had inflammation of ileum and colon, with a significant difference compared to that in patients under 6 years old (19% (5/27) , χ(2)=9.455, P=0.003). Also, the location of bowel inflammation among the four groups were significantly different (χ(2)=21.120, P<0.01). (5) Noncaseating granulomas were found in 15 (30%) CD patients, and crypt abscess was found in 11 (44%) UC patients. (6) Among the 24 patients whose genes were analyzed by high throughput sequencing, 12 had pathogenic single gene mutation. (7) There were 25 patients treated with total enteral nutrition. Among the 25 patients treated with thalidomide, 20 (80%) had clinical remission or partial remission. Among the 19 CD patients treated with infliximab (IFX), 14 had clinical remission at the 6(th) week of treatment, and the proportion of remission maintenance at the 30(th) week of treatment was 12/14. (8) The rate of clinical remission or partial remission was 64% (23/36) in the 0 -<2 years old group, 8/10 in the 2 -<6 years old group, 11/12 in the 6 -<10 years old group, and 83% (24/29) in the 10 -<18 years old group. Conclusions: The proportion of CD was higher than that of UC in this study. Infant onset inflammatory bowel disease was more likely to present with perianal lesions, and was usually associated with leukocytosis, thrombocytosis and anemia, and has high possibility of single gene mutation. IFX may be effective in treating CD.

Impact of immune-mediated diseases in inflammatory bowel disease and implications in therapeutic approach

Inflammatory bowel diseases (IBD) belong to the group of immune-mediated diseases (IMIDs). The effect of associated IMIDs in the prognosis in IBD is nowadays unknown. To describe IMIDs associated to IBD patients and evaluate differences linked to the presence or absence of IMIDs. A unicentric retrospective descriptive study was designed. A cohort of 1,448 patients were categorized according to the presence of IMIDs. Clinical characteristics were obtained from IBD database. Univariate and multivariate analysis were performed. 385 patients were diagnosed with associated IMIDs while 1,063 had no associated IMIDs. A prevalence of 26.6% IMIDs associated to IBD was observed. Asthma, skin psoriasis and rheumatoid diseases were most commonly found. Factors associated to the presence of IMIDs were women (OR 1.48; 95 CI 1.17–1.87) and Crohn’s disease (OR 1.35; 95 CI 1.07–1.70). Patients with associated IMIDs required more immunomodulator (OR 1.61; 95 CI 1.27–2.43) and biological treatment (OR 1.81; 95 CI 1.47–2.43). More surgical risk was observed in multivariate analysis in those patients diagnosed with IMIDs prior to the onset of IBD (OR 3.71; 95% CI 2.1–6.56). We considered the presence of IMIDs a poor prognostic factor and suggest a closer monitoring of these patients.

465 Real-world risk of new onset inflammatory bowel disease among psoriasis patients exposed to interleukin 17 inhibitors

465 Real-world risk of new onset inflammatory bowel disease among psoriasis patients exposed to interleukin 17 inhibitors

Intestinal dysbiosis in pediatric Crohn's disease patients with IL10RA mutations.

BACKGROUNDSeveral studies have employed animal models to explore the association between microbiota and interleukin (IL) 10 signaling; however, limited information is available about the human microbiome.AIMTo characterize the microbiome in patients with IL10RA mutations and to explore the association between gut dysbiosis and disease severity.METHODSFecal samples were collected from patients who were diagnosed with loss-of-function mutations in the IL10RA gene between January 2017 and July 2018 at the Children's Hospital of Fudan University. Age-matched volunteer children were recruited as healthy controls. Patients with Crohn's disease (CD) were used as disease controls to standardize the antibiotic exposure. Microbial DNA was extracted from the fecal samples. All analyses were based on the 16S rRNA gene sequencing data.RESULTSSeventeen patients with IL10RA mutations (IL10RA group), 17 patients with pediatric CD, and 26 healthy children were included. Both patients with IL10RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability. The relative abundance of Firmicutes was substantially increased in the IL10RA group (P = 0.02). On further comparison of the relative abundance of taxa between patients with IL10RA mutations and healthy children, 13 taxa showed significant differences. The IL10RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD.CONCLUSIONIn patients with IL10RA mutations and early onset inflammatory bowel disease, gut dysbiosis shows a moderate association with disease severity.

Risk of Prevalent Asthma among Children Affected by Inflammatory Bowel Disease: A Population-Based Birth Cohort Study.

Literature on the risk of asthma among children with inflammatory bowel disease (IBD) is limited and has reported discording results. To the best of our knowledge, no previous study has evaluated the association between asthma and childhood onset IBD, focusing on pediatric IBD with onset between 10 and 17 years, early-onset IBD (EO-IBD) between 0 and 9 years, and very early-onset IBD (VEO-IBD) between 0 and 5 years, all conditions characterized by different clinical progressions. A nested matched case-control design on a longitudinal cohort of 213,515 newborns was adopted. Conditional binomial regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) of asthma among children with IBD compared with controls. We found 162 children with IBD and 1620 controls. Overall, childhood onset IBD was associated with increased risks of being affected by asthma (OR: 1.49 95% CI 1.05–2.12), although a significant risk was only present among males (OR: 1.60 95% CI 1.02–2.51). Children with Crohn’s disease and ulcerative colitis had similarly increased risks, although they failed to attain statistical significance. Risks of asthma based on age at IBD onset were inversely related to age, with the lowest non-significant risks for pediatric IBD and EO-IBD, while children affected by VEO-IBD had the highest risk of asthma (OR: 2.75 95% CI 1.26–6.02). Our study suggests the presence of a higher prevalence of asthma among both male children with IBD and children with VEO-IBD. It could be advisable to pay greater attention to possible respiratory symptoms among these categories at higher risk.

Covering the Cover

Covering the Cover

Monogenic Very Early Onset Inflammatory Bowel Disease in Children. A Report of Two Cases and Literature Review

Monogenic Very Early Onset Inflammatory Bowel Disease in Children. A Report of Two Cases and Literature Review

The Role of Gut Microbiota Biomodulators on Mucosal Immunity and Intestinal Inflammation.

Alterations of the gut microbiota may cause dysregulated mucosal immune responses leading to the onset of inflammatory bowel diseases (IBD) in genetically susceptible hosts. Restoring immune homeostasis through the normalization of the gut microbiota is now considered a valuable therapeutic approach to treat IBD patients. The customization of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics and faecal microbiota transplantation, is therefore considered to support current therapies in IBD management. In this review, we will discuss recent advancements in the understanding of host−microbe interactions in IBD and the basis to promote homeostatic immune responses through microbe-targeted therapies. By considering gut microbiota dysbiosis as a key feature for the establishment of chronic inflammatory events, in the near future it will be suitable to design new cost-effective, physiologic, and patient-oriented therapeutic strategies for the treatment of IBD that can be applied in a personalized manner.

Natural History of Very Early Onset Inflammatory Bowel Disease in North America: A Retrospective Cohort Study.

The incidence of very early onset inflammatory bowel disease (VEOIBD) is increasing, yet the phenotype and natural history of VEOIBD are not well described. We performed a retrospective cohort study of patients diagnosed with VEOIBD (6 years of age and younger) between 2008 and 2013 at 25 North American centers. Eligible patients at each center were randomly selected for chart review. We abstracted data at diagnosis and at 1, 3, and 5 years after diagnosis. We compared the clinical features and outcomes with VEOIBD diagnosed younger than 3 years of age with children diagnosed with VEOIBD at age 3 to 6 years. The study population included 269 children (105 [39%] Crohn's disease, 106 [39%] ulcerative colitis, and 58 [22%] IBD unclassified). The median age of diagnosis was 4.2 years (interquartile range 2.9-5.2). Most (94%) Crohn's disease patients had inflammatory disease behavior (B1). Isolated colitis (L2) was the most common disease location (70% of children diagnosed younger than 3 years vs 43% of children diagnosed 3 years and older; P = 0.10). By the end of follow-up, stricturing/penetrating occurred in 7 (6.6%) children. The risk of any bowel surgery in Crohn's disease was 3% by 1 year, 12% by 3 years, and 15% by 5 years and did not differ by age at diagnosis. Most ulcerative colitis patients had pancolitis (57% of children diagnosed younger than 3 years vs 45% of children diagnosed 3 years and older; P = 0.18). The risk of colectomy in ulcerative colitis/IBD unclassified was 0% by 1 year, 3% by 3 years, and 14% by 5 years and did not differ by age of diagnosis. Very early onset inflammatory bowel disease has a distinct phenotype with predominantly colonic involvement and infrequent stricturing/penetrating disease. The cumulative risk of bowel surgery in children with VEOIBD was approximately 14%-15% by 5 years. These data can be used to provide anticipatory guidance in this emerging patient population.