Onset Inflammatory Bowel Disease Research Articles

Labour market participation and income in patients with IBD onset before young adulthood - the role of disease severity and mental health.

Only few studies have examined the socioeconomic consequences of being diagnosed with inflammatory bowel disease (IBD) in childhood or youth. Disease severity has been linked to lower earnings, but little attention has been paid to comorbid mental health conditions. The aim is to examine labour market participation (LMP) and income in patients with IBD-onset in childhood or youth and examine how disease severity and mental health conditions affects LMP. In this register-based cohort study, we included patients with IBD-onset before 25 years of age and matched comparators. We estimated the relative risk (RR) of having low LMP and the median yearly income from ages 26 to 30. RR of low LMP was also assessed in subgroups of patients based on disease severity (severe/non-severe) and mental health conditions (yes/no). A total of 3,398 patients with IBD and 28,207 comparators were included. Overall, patients with IBD more often had low LMP (16.4% vs 14.4% in comparators), but slightly higher income (median yearly income difference at age 30: 1,141 Euro [95% CI: 483-1,798]). In subgroup analyses, only patients with severe IBD had higher risk of low LMP (RR 1.46 [95% CI 1.23-1.72]), not patients with non-severe IBD. Among patients with severe disease and mental health conditions 46% had low LMP (RR 5.03 [95% CI 4.38-5.78]). Patients with IBD more often had low LMP, but their income was not affected. The subgroup of patients with severe disease and mental health conditions had the highest risk of low LMP.

Comprehensive data optimization and risk prediction framework: machine learning methods for inflammatory bowel disease prediction based on the human gut microbiome data.

Over the past decade, the prevalence of inflammatory bowel disease (IBD) has significantly increased, making early detection crucial for improving patient survival rates. Medical research suggests that changes in the human gut microbiome are closely linked to IBD onset, playing a critical role in its prediction. However, the current gut microbiome data often exhibit missing values and high dimensionality, posing challenges to the accuracy of predictive algorithms. To address these issues, we proposed the comprehensive data optimization and risk prediction framework (CDORPF), an ensemble learning framework designed to predict IBD risk based on the human gut microbiome, aiding early diagnosis. The framework comprised two main components: data optimization and risk prediction. The data optimization module first employed triple optimization imputation (TOI) to impute missing data while preserving the biological characteristics of the microbiome. It then utilized importance-weighted variational autoencoder (IWVAE) to reduce redundant information from the high-dimensional microbiome data. This process resulted in a complete, low-dimensional representation of the data, laying the foundation for improved algorithm efficiency and accuracy. In the risk prediction module, the optimized data was classified using a random forest (RF) model, and hyperparameters were globally optimized using improved aquila optimizer (IAO), which incorporated multiple strategies. Experimental results on IBD-related gut microbiome datasets showed that the proposed framework achieved classification accuracy, recall, and F1 scores exceeding 0.9, outperforming comparison models and serving as a valuable tool for predicting IBD onset risk.

Very early onset versus pediatric onset inflammatory bowel disease: a prospective cohort analysis

Very early onset versus pediatric onset inflammatory bowel disease: a prospective cohort analysis

NPSR1 promotes chronic colitis through regulating CD4+ T cell effector function in inflammatory bowel disease

BackgroundNeuropeptide S receptor 1 (NPSR1) has been implicated in the the onset of inflammatory bowel disease (IBD), though its exact mechanism remains unclear. This study investigates the role of NPSR1 in regulating CD4+ T cell effector function in IBD. MethodsPeripheral blood and colonic mucosal biopsies from IBD patients, as well as dextran sodium sulfate (DSS)-induced mouse colitis models, were analyzed to assess the effects of NPSR1 on colitis and CD4+ T cell-mediated immune responses. NPSR1 knockdown was conducted both in vitro and in vivo to elucidate underlying mechanisms. Expression of NPSR1 and CD4+ T cell-related factors was measured using quantitative real-time PCR, immunoblotting, cytometric bead array, immunofluorescence, and immunohistochemistry. CD4 + T cell effector functions were evaluated through flow cytometry, EdU incorporation assay, Annexin V-FITC/PI staining, and transwell assay. ResultsNPSR1 expression was elevated in the intestinal tissues from IBD patients. Its downregulation provided protection in DSS-induced mouse colitis models. NPSR1 correlated positively with CD4 + T cell-mediated inflammation, and its knockdown reduced CD4+ T cell-mediated immune responses and inhibited CD4+ T cell differentiation. Additionally, NPSR1 knockdown decreased CD4+ T cell proliferation, increased apoptosis, and enhanced CCL2-induced migration in vitro, while significantly reducing Th1 cell chemotaxis in vivo. ConclusionsThis study demonstrates that NPSR1 promotes chronic colitis by regulating CD4 + T cell effector functions in IBD, offering potential new therapeutic strategies for IBD treatment.

Air pollution exposure and inflammatory bowel disease: a systematic literature review of epidemiological and mechanistic studies

This systematic literature review investigates the relationship between air pollution exposure and inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC). Despite the growing concern over air pollution's impact on various health outcomes, studies specifically addressing effects on the digestive system, particularly IBD, are relatively rare. This review aims to synthesize the current knowledge on this topic, focusing on the mechanisms underlying these associations and the role of different air pollutants. Following PRISMA guidelines, a systematic literature search of PubMed and Web of Science databases was conducted, yielding 13 epidemiological studies and six mechanistic (toxicological) studies meeting the inclusion criteria. The epidemiological studies examined associations between IBD and various air pollutants, including PM2.5 (particles with an aerodynamic diameter smaller than, or equal to, 2.5 µm), PM10 (particles with an aerodynamic diameter smaller than, or equal to, 10 µm), PM2.5–10 (coarse particles with an aerodynamic diameter in the range of 2.5–10 µm), BC (black carbon), NO2 (nitrogen dioxide), NO (nitrogen monoxide), NOx (nitrogen oxides), N2O (nitrous oxide), CO (carbon monoxide), SO2 (sulfur dioxide), VOC (volatile organic compounds), O3 (ozone), Ox (oxidant capacity), and traffic load. Study methodologies varied among these 13 epidemiological studies, including four cohort studies, two ecological studies, three case-control studies, two studies using two-sample Mendelian randomization, and two longitudinal time-series studies. Eight studies investigated associations with Crohn's disease and ulcerative colitis separately, while five studies analyzed IBD as a whole without distinguishing between CD and UC. Eleven studies found statistically significant associations between air pollution exposure and IBD, although inconsistent results were found in several of these studies. A total number of six mechanistic (toxicological) studies were retrieved. Among these six studies, five were using particulate matter as exposure metric, and one was based on NO2 and O3 as exposure metrics. With a combination of animal, human, and in vitro studies, the results in terms of biological mechanisms indicate that air pollution exposure influences the composition of the gut microbiome, altering metabolic functions within the gut, and creates immunological reactions with inflammation contributing to the development of IBD. Consequently, the results suggest a link between air pollution exposure and both the onset and exacerbation of IBD. However, differences in study design, exposure assessment, and pollutant types make it challenging to draw any firm conclusions. Moreover, the lack of multi-pollutant models in most epidemiological studies makes it difficult to estimate the individual effect of specific air pollutants. This review highlights the need for further research utilizing robust study designs and standardized exposure assessment methods to better understand the impact of air pollution on IBD. By elucidating these associations, policymakers and healthcare professionals can develop effective strategies to mitigate the adverse effects of air pollution on digestive health.

The Role of Diet in Inflammatory Bowel Disease Onset, Disease Management, and Surgical Optimization.

The concept of using diet as therapy in inflammatory bowel disease is of interest to clinicians and patients. Once considered to play a minor role, diet is now known to not only affect disease onset but may also serve as a therapeutic tool for inducing and maintaining remission and improving surgical outcomes. Further research is needed to fully elucidate how, when, and in whom diet therapies may be best applied to improve clinical and disease outcomes. The aim of this review was to summarize current research findings and serve as a tool to help facilitate patient-clinician conversations.

Family reflections: research gives back childhood: a family's experience with very early onset inflammatory bowel disease.

Family reflections: research gives back childhood: a family's experience with very early onset inflammatory bowel disease.

Patients with Inflammatory Bowel Disease Show Fewer Sex-Related Differences in Their Dietary Behavior Than the General Population: A Qualitative Analysis.

Since diet is generally recognized as an important factor directly modulating the gut microbiome, it is also considered a potential environmental triggering factor for the pathogenesis and onset of inflammatory bowel disease (IBD). While the habitual and sex-related dietary behavior of the general population has been the subject of extensive study and reporting, data on IBD patients' dietary behavior and especially its sex-related differences are underrepresented. However, as diet is an important factor in the course of IBD, we hypothesized that men and women with IBD have a different dietary profile than the general population. We performed a cohort analysis of a monocentric, cross-sectional study and compared the sex-related dietary behavior of 82 IBD patients (n = 40 women) to a sex- and age-matched cohort of the general German population [n = 328 (n = 160 women)]. Further on, disease-related quality of life and fecal calprotectin were correlated to the IBD patients' dietary behavior. While sex-related dietary behavior was frequently of statistical difference in the general population within the IBD cohort, only minor numerical differences were observed between the sexes, which were rarely statistically significant. However, correlation analyses of disease-related quality of life (IBDQ) and diet revealed significant differences in male IBD patients but not in female IBD patients (p = 0.007; r = 0.409 for energy intake (kJ/d); p = 0.003, r = 0.449 for adherence to Mediterranean diet). The dietary behavior of IBD patients showed more similarity between the sexes than the general German population. Distinct sex-related trends and differences in correlation with disease parameters demonstrated a significant difference for an adaptive dietary behavior, especially in IBD men.

Dysregulated NOX1-NOS2 activity as hallmark of ileitis in mice

Inflammation of the ileum, or ileitis, is commonly caused by Crohn’s disease (CD) but can also accompany ulcerative colitis (backwash ileitis), infections or drug-related damage. Oxidative tissue injury triggered by reactive oxygen species (ROS) is considered part of the ileitis etiology. However, not only elevated ROS but also permanently decreased ROS are associated with inflammatory bowel disease (IBD). While very early onset IBD (VEO-IBD) is associated with a spectrum of NOX1 variants, how NOX1 inactivation contributes to disease development remains ill-defined. Besides propagating signaling responses, NOX1 provides superoxide for peroxynitrite formation in the epithelial barrier. Here we report that NOX4, an H2O2-generating NADPH oxidase with documented tissue protective effects in the intestine and other tissues, limits the generation of ileal peroxynitrite by NOX1/NOS2. Deletion of NOX4 leads to persistent peroxynitrite excess, hyperpermeability, villus blunting, muscular hypertrophy, chemokine/cytokine upregulation and dysbiosis. Conversely, SAMP1/YitFc mice, a CD-like ileitis model, showed age-dependent NOX1/NOS2 downregulation preventing ileal peroxynitrite formation in homeostasis and LPS-induced acute inflammation. Deficiency in NOX1 correlated with the upregulation of antimicrobial peptides, suggesting that ileal peroxynitrite acts as chemical barrier and microbiota modifier in the ileum.

The use of isotretinoin increases the risk of inflammatory bowel disease. A narrative review

Introduction: Acne vulgaris represents a prevalent dermatological condition capable of exerting a profound impact on an individual's quality of life. Isotretinoin, despite its well-established status as a highly effective remedy for severe acne, concerns surrounding the potential linkage with inflammatory bowel disease (IBD) have led to inquiries about its association. Objective: The primary objective of this review is to critically assess the existing body of evidence pertaining to the efficacy and safety of isotretinoin, with a particular emphasis on its association with IBD. Methods: A literature review was undertaken to examine the utilization of isotretinoin in the management of acne and to evaluate the subsequent risk of inflammatory bowel disease, aiming to determine the relevance of considering this factor when utilizing this treatment. Conclusions: Isotretinoin is widely recognized as the most effective therapeutic approach to treat acne. This compound competently addresses all underlying factors contributing to acne pathogenesis. Over time, extensive deliberation has arisen concerning concerns related to its potential correlation with the onset of IBD. The currently available evidence conveys a paucity of substantial scientific support for a causal relationship between the use of isotretinoin and the development of IBD.

A Novel Case of SHORT Syndrome Presenting with Very Early Onset Inflammatory Bowel Disease (VEO-IBD)

Herein we report a novel case of SHORT syndrome with very early onset inflammatory bowel disease (VEOIBD). He presented with hematochezia since the first months of life for which he was diagnosed with cow milk allergy that did not respond to treatment. He underwent a colonoscopy confirming the diagnosis of ulcerative colitis (UC). His past medical history was also remarkable with delayed growth since 6 months of age and frequent hospitalizations due to recurrent fever, gastroenteritis, and anemia with no history of recurrent infectious episodes. Despite appropriate treatment for UC and partial improvement in his bowel habits and nutrition, there was no improvement in his growth status and he was found to have failure to thrive. The patient further underwent genetic test evaluation and a novel heterozygous missense mutation was detected in the PIK3R1 gene (c.2076A>C, P. Lys692Asn) confirming the diagnosis of SHORT syndrome. He got appropriate treatment and is currently doing well, in good condition and is under regular monthly follow-up.

Self-Compassion in Adolescents and Young Adults With Inflammatory Bowel Disease: Relationship of Self-Compassion to Psychosocial and Physical Outcomes.

Adolescents and young adults (AYAs) diagnosed with inflammatory bowel disease (IBD) are at an increased risk for poor physical and mental health due to the complexity of pediatric onset IBD and the unique developmental challenges of this period of life. Self-compassion is increasingly recognized as having an important role in explaining health outcomes and well-being across a range of populations. This study examines the relationship between self-compassion and psychosocial and physical health outcomes in AYAs with IBD. In this cross-sectional study, AYAs with IBD aged 15 to 25 years completed an online survey between February 2020 and October 2021. Questionnaires included the Self-Compassion Scale-Short Form, Patient-Reported Outcomes Measurement Information System (PROMIS) measures for psychosocial, physical and global health outcomes, and IBD disease activity indices. AYAs with higher levels of self-compassion were found to have better psychosocial (ie, anxiety, depressive symptoms, psychological stress, physical stress, peer relationships), physical (ie, fatigue), and global health outcomes. Self-compassion was a significant independent predictor of anxiety (β = -5.80, P = < .001), depressive symptoms (β = -7.09, P = < .001), psychological stress (β = -4.66, P = < .001), physical stress (β = -3.19, P = < .001), peer relationships (β = 3.39, P = .003), fatigue (β = -2.05, P = .019), and improved global health (β = 5.15, P = < .001). This study offers preliminary support for the importance of self-compassion in AYAs with IBD and demonstrates the need for further research in this area.

Chronic binge drinking-induced susceptibility to colonic inflammation is microbiome-dependent

ABSTRACT Alterations in intestinal permeability and the gut microbiome caused by alcohol abuse are associated with alcoholic liver disease and with worsening of inflammatory bowel diseases (IBD) symptoms. To resolve the direct effects of chronic ethanol consumption on the colon and its microbiome in the absence of acute or chronic alcohol-induced liver disease, we developed a mouse model of chronic binge drinking that uncovers how alcohol may enhance susceptibility to colitis via the microbiota. Employing daily ethanol gavage, we recapitulate key features of binge ethanol consumption. We found that binge ethanol drinking worsens intestinal infection, colonic injury and inflammation, and this effect persists beyond the drinking period. Using gnotobiotics, we showed that alcohol-driven susceptibility to colitis is microbiota-dependent and transferable to ethanol-naïve mice by microbiome transplantation. Allobaculum spp. expanded in binge drinking mice, and administration of Allobaculum fili was sufficient to enhance colitis in non-drinking mice. Our study provides a model to study binge drinking-microbiota interactions and their effects on host disease and reinforces the pathogenic function of Allobaculum spp. as colitogenic bacteria. Our findings illustrate how chronic binge drinking-induced alterations of the microbiome may affect susceptibility to IBD onset or flares.

New Onset Inflammatory Bowel Disease Risk Following Bariatric Surgery: A Systematic Review and Meta-Analysis of Observational Studies

Background: While bariatric surgery may reduce obesity-associated inflammation, alterations in gut microbiome and nutrition could impact inflammatory bowel disease (IBD) risk. This study aimed to investigate the association between bariatric surgery and new onset IBD. Methods: A systematic review and meta-analysis of observational studies was conducted from inception to 31 January 2024. Risk estimates were pooled using a DerSimonian and Laird random-effects model, and adjusted hazards ratios (HRs) with corresponding 95% confidence interval (CI) were reported. The modified Newcastle-Ottawa Quality Assessment Scale (NOS) was used to examine the risk of bias. Results: Of 98 articles screened, four studies comprising 4,727,600 participants were included in the systematic review and two studies in the meta-analysis. Included studies had high quality and low risk of bias according to NOS. The pooled analysis revealed a significant risk of new onset IBD (HR: 1.28, 95% CI: 1.04–1.53, I2 = 74.9%), particularly Crohn’s disease (HR: 1.75, 1.59–1.92, I2 = 0), following bariatric surgery, but no significant risk of ulcerative colitis (HR: 0.93, 0.75–1.11, I2 = 11.5%). Conclusions: This meta-analysis found that bariatric surgery was associated with a higher risk of developing Crohn’s disease. Patients should be counseled on IBD risk pre-surgery, and symptomatic patients should be evaluated post-surgery to enable early diagnosis and management.

Clinicopathologic Features of Primary Immunodeficiency Monogenic Disease-related Very Early Onset Inflammatory Bowel Disease: Focus on Gastrointestinal Histologic Features in IFIH1 Mutations.

Very early onset inflammatory bowel disease (VEO-IBD) is a clinical term referring to IBD-like symptomatology arising in children younger than 6 years. VEO-IBD may be due to polygenic etiology in "pure" IBD (Crohn disease-CD and ulcerative colitis-UC), or it may be caused by primary immunodeficiency underlined by monogenic disease. Primary immunodeficiency monogenic diseases have a Mendelian inheritance and affect the immune system with multiorgan morbidity and possible effects on the gastrointestinal system. Primary Immunodeficiency monogenic diseases differ from "pure" IBD as the latter primarily affect the gastrointestinal tract with mitigated extraintestinal symptomatology. Since their first description, primary immunodeficiency monogenic diseases, although rare, have been the subject of increasing interest due to their dramatic phenotype, difficulty in reaching a timely diagnosis, and specific therapeutic approach. In this paper, we present a brief review of primary immunodeficiency monogenic diseases, focusing on to their clinicopathologic features as well as delving, in greater detail, into monogenic diseases caused by IFIH1 mutations. The clinicopathologic features of 4 patients with IFIH1, a gene involved in interferon pathway deficiency, will be described using a histologic pattern of damage approach confirming the need to avoid the histologic diagnosis of VEO-IBD in children younger than 6 years.

Impact of Helicobacter pylori Eradication on Inflammatory Bowel Disease Onset and Disease Activity: To Eradicate or Not to Eradicate?

Helicobacter pylori infection has significant epidemiological relevance due to the carcinogenic nature of this bacterium, which is potentially associated with cancer. When detected, it should ideally be eradicated using a treatment that currently involves a combination of gastric acid suppressors and multiple antibiotics. However, this treatment raises questions regarding efficacy and safety profiles in patients with specific comorbidities, including inflammatory bowel diseases (IBD). Eradication therapy for H. pylori includes components associated with adverse gastrointestinal events, such as Clostridioides difficile colitis. This necessitates quantifying this risk through dedicated studies to determine whether this antimicrobial treatment could be significantly associated with IBD relapse or exacerbation of pre-existing IBD, as well as whether it could potentially lead to the de novo onset of IBD. Although the available evidence is reassuring about the safety of eradication therapy in patients with IBD, it is limited, and there are no specific recommendations for this particular situation in the leading international IBD and H. pylori guidelines. Therefore, studies need to evaluate the efficacy and safety profiles of the available antimicrobial regimens for H. pylori eradication in patients with IBD, both in clinical trial settings and in real-life studies.

Epidemiology of Elderly Onset IBD: A Nationwide Population-Based Cohort Study

We examined the incidence and natural history of patients with very elderly onset (herein referred to as very late-onset) inflammatory bowel diseases (IBDs) (≥ 70 years of age at diagnosis), compared with patients diagnosed between 60 and 69 years of age in Denmark. In the Danish National Patient Register, between 1980 and 2018, we identified all individuals ≥ 60 years of age with newly diagnosed Crohn's disease (CD) and ulcerative colitis (UC) and examined trends in incidence, cumulative risk of hospitalization, treatment patterns, IBD-related surgery, serious infection, cancer and cardiovascular and venous thromboembolic risks among very late-onset (70-79 years of age or 80+ years) vs late-onset (60-69 years of age) IBD, using nonparametric competing risk analysis treating death as competing risk. We identified 3459 patients with onset of CD at ≥60 years of age (47% ≥ 70 years of age) and 10,774 patients with onset of UC ≥60 years of age (51% ≥ 70 years of age). Over the last 3 decades, incidence changes for very late-onset and late-onset IBD have followed the same patterns. Also, both for CD and UC, cumulative incidence of IBD-related hospitalization and corticosteroid use was comparable in very late-onset vs late-onset patients. However, the burden of disease-modifying therapy, either immunomodulator or tumor necrosis factor antagonist use, and major IBD-related surgery was significantly lower in patients with very late-onset than in late-onset IBD. On the other hand, the 5-year risk of serious infections and cardiovascular events was higher in patients with very late-onset IBD. This nationwide cohort study shows that patients diagnosed with very late-onset (≥ 70 years of age) IBD have a higher relative burden of disease- and aging-related complications, with limited use of steroid-sparing strategies and surgery, compared with late-onset IBD.

Novel Insights into the Interaction between Enteropathogenic Bacteria, Pyroptosis and IBD.

Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease of the intestinal tract. The complex pathophysiological mechanisms of IBD include genetic susceptibility, environmental factors, and abnormal immune response of the gut microbiota. Gut microbiota forms a metabolic organ that contributes to human health by performing various physiological functions. The development of IBD is closely linked to the imbalance of gut microbiota. In IBD patients, this imbalance is mainly characterized by an increased abundance of pro-inflammatory microorganisms, specifically enteropathogenic bacteria. Pyroptosis is a form of programmed cell death that can be initiated by microbial infection or host factors. It occurs mostly after intracellular infection with bacteria or pathogens. Other than cell death, its primary effect is to release inflammatory mediators that trigger an inflammatory response in the host. Pyroptosis is an important component of innate immunity and can protect against intracellular risk factors via the inflammatory response. However, excessive activation can cause disease. Previous studies of IBD have indicated a complex relationship between gut microbiota and pyroptosis. Some enteropathogenic bacteria can activate the host's immune system to clear infected cells. This inhibits the proliferation of enteropathogenic bacteria by inducing pyroptosis and restoring the balance of gut microbiota. However, the initial inflammatory response and damage to the integrity of the intestinal barrier are crucial factors that elicit the onset of IBD and favor its progression. This review summarizes research on the role of several common enteropathogenic bacteria in the development of IBD through their induction of host cell pyroptosis. A better understanding of the complex interactions between gut microbiota and pyroptosis should lead to the identification of new targets and treatment options for IBD.

Infantile and Very Early Onset Inflammatory Bowel Disease: A Multicenter Study.

This study described disease characteristics and long-term outcomes in patients diagnosed with very early onset inflammatory bowel disease (VEOIBD) (diagnosed before 6 years of age) and infantile-IBD (before 2 years). Cases from 21 centers worldwide diagnosed with VEOIBD (2008-2018), with minimum 2 years of follow-up, were retrospectively reviewed. The cohort included 243 patients (52% males, median follow-up of 5.8 [range 2-18] years, including 69 [28%]) with infantile-IBD. IBD subtypes included Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU) in 30%, 59%, and 11%, respectively. Among patients with CD, 94% had colonic involvement, and among patients with UC/IBDU, 75% had pancolitis. Patients with infantile-IBD presented with higher rates of IBDU, lower hemoglobin and albumin levels, and higher C-reactive protein, and had lower response rates to first-induction therapy and corticosteroids therapy (P < .05 for all). Colectomy and diversion surgeries were performed in 11% and 4%, respectively, with no significant differences between age groups. Corticosteroid-free remission rates were 74% and 78% after 3 and 5 years, respectively, and 86% at end of follow-up. Genetic testing was performed in 96 (40%) patients. Among tested population, 15 (16%) were identified with monogenic disease. This group demonstrated lower response rates to induction therapies, higher rates of surgical intervention, and higher rates of major infections (P < .05 for all). Patients with VEOIBD, including infantile-IBD, exhibit low rate of complications and surgical interventions at the long term. Patients with monogenic IBD are at risk for more severe disease course.

MYO5B gene mutations may promote the occurrence of very early onset inflammatory bowel disease: a case report

BackgroundWith recent advances in gene sequencing technology, more than 60 genetic mutations associated with very early onset inflammatory bowel disease (VEO-IBD) have been reported. Most of the genes are associated with immune deficiencies. The Myosin 5B (MYO5B) gene is primarily involved in cell motility and material transport which is associated with congenital intractable diarrhea and cholestasis. No studies have examined the relationship between the MYO5B gene and VEO-IBD. We report a case of a child with a mutation in the MYO5B gene who was diagnosed with VEO-IBD, then we investigated the association between the MYO5B gene and VEO-IBD.Case presentationA 7-month-old baby girl with a chief complaint of “blood in the stool for more than 4 months and vaginal pus and blood discharge for 3 weeks” was diagnosed with VEO-IBD, and her symptoms improved after treatment with mesalazine. The whole-exome sequencing was performed with peripheral blood. Immunohistochemistry was performed on the terminal ileal tissue. Western blotting, quantitative polymerase chain reaction (Q-PCR) and immunofluorescence were performed with cultured organoid tissue from the terminal ileum. Whole-exome sequencing identified heterozygous missense of MYO5B variant of unknown significance (p. [I769N]; [T1546M]). Immunohistochemistry revealed a significant decrease in the expression of MYO5B protein in the terminal ileum of the child with MYO5B mutation; Q-PCR revealed a decrease in the mRNA levels of occludin and ZO-1 and both the mRNA levels and protein levels of MYO5B was downregulated in the patient. Immunofluorescence images showed that MYO5B gene mutation disrupted the apical delivery of transporters SGLT1, NHE3 and AQP7.ConclusionsMYO5B gene mutation leading to the downregulation of MYO5B protein may promote the occurrence of VEO-IBD by decreasing mRNA and protein levels of intestinal tight junction genes and dislocating the apical transporters.