Association between Killer Immunoglobulin-like receptor genes and susceptibility to inflammatory bowel disease: An updated meta-analysis.

Background: Several studies have associated members of the KIR genes as susceptibility factors to inflammatory bowel diseases (IBD): ulcerative colitis (UC) and Crohn's disease (CD). Objectives: To assess the association between the presence and absence KIR genes and IBD susceptibility through a meta-analysis. Method: A systematic search was performed through the PubMed, Scopus, and Web of Science databases to obtain relevant articles published before March 2024. Associations between genes and susceptibility to IBDs were estimated by OR with 95 % CI. Results: We found positive associations of the KIR2DS1 and KIR2DS3 genes with susceptibility to UC, while the KIR2DL3 and KIR2DS4 full genes showed a negative association. In addition, the KIR2DS1, KIR2DS3, KIR2DS4, KIR2DS5, and KIR3DS1 genes showed a positive association with susceptibility to CD, whereas the KIR2DL1 gene showed a negative association. Conclusions: Our meta-analysis indicates that individuals carrying the KIR2DS1 and KIR2DS3 genes exhibit increased susceptibility to UC, whereas carriers of the KIR2DS1, KIR2DS3, KIR2DS4, KIR2DS5, and KIR3DS1 genes are more prone to CD. However, further studies are required to clarify the role of the KIR genes and their corresponding ligands in the pathology of IBD.

Baseline Characteristics of Adult Patients Treated and Never Treated with Teduglutide in a Multinational Short Bowel Syndrome and Intestinal Failure Registry.

The Short Bowel Syndrome (SBS) Registry (NCT01990040) is a multinational real-world study evaluating the long-term safety of teduglutide in patients with SBS and intestinal failure (SBS-IF) in routine clinical practice. This paper describes the study methodology and baseline characteristics of adult patients who have (ever-treated) or have never (never-treated) received teduglutide. A total of 1411 adult patients (679 ever-treated; 732 never-treated) were enrolled at 124 sites across 17 countries. The mean (standard deviation [SD]) age at enrollment was 55.4 (15.46) years, and 60.2% of patients were women. Crohn's disease was the most common cause of major intestinal resection in both ever-treated (34.1%) and never-treated patients (20.4%). A similar proportion of ever-treated and never-treated patients had a prior history of colorectal polyps (2.7% vs. 3.6%), whereas proportionally fewer ever-treated patients reported a history of colorectal cancer (1.8% vs. 6.2%) or any malignancy (17.7% vs. 30.0%) than never-treated patients. Never-treated patients received a numerically greater mean (SD) volume of parenteral nutrition and/or intravenous fluids than ever-treated patients (12.4 [8.02] vs. 10.1 [6.64] L/week). Ever-treated patients received a mean teduglutide dosage of 0.05 mg/kg/day. This is the first report of patient baseline characteristics from the SBS Registry, and the largest cohort of patients with SBS-IF to date. Overall, ever-treated and never-treated patients had similar baseline characteristics. Differences between treatment groups may reflect variations in patient selection and degree of monitoring.

Co-occurrence of oral pemphigus vulgaris and herpes simplex virus infection in a young patient with Crohn's disease: report of a rare case of oral lesions during anti-TFN alpha and immunomodulator therapy.

BACKGROUND: Pemphigus vulgaris (PV) is a potentially life-threatening mucocutaneous autoimmune disease that affects desmoglein-1 and desmoglein-3, leading to intraepithelial vesiculobullous lesions. In the oral mucosa, PV lesions can mimic other diseases such as mucous membrane pemphigoid, other forms of pemphigus, recurrent aphthous stomatitis, erythema multiforme, Stevens-Johnson syndrome, and virus-induced ulcers like herpes simplex virus (HSV), making diagnosis challenging. The co-occurrence of PV with Crohn's disease is rare and predominantly seen in younger patients. The therapeutic mainstay for both PV and Crohn's disease usually involves systemic corticosteroids combined with immunosuppressants and immunobiological drugs. Literature indicates that the use of these drugs, particularly TNF-alpha inhibitors, for managing autoimmune diseases like Crohn's can potentially induce other autoimmune diseases known as autoimmune-like syndromes, which include episodes of lupus-like syndrome and inflammatory neuropathies. There are few cases in the literature reporting the development of PV in individuals with CD undergoing infliximab therapy. CASE REPORT: A young female with severe Crohn's disease, treated with the TNF-alpha inhibitor infliximab, developed friable pseudomembranous oral ulcerations. Histopathological and immunofluorescence analyses confirmed these as PV. The treatment included clobetasol propionate and low-level photobiomodulation, which resulted in partial improvement. The patient later experienced severe intestinal bleeding, requiring intravenous hydrocortisone therapy, which improved both her systemic condition and oral lesions. Weeks later, new ulcerations caused by herpes virus and candidiasis were identified, leading to treatment with oral acyclovir, a 21-day regimen of oral nystatin rinse, and photodynamic therapy, ultimately healing the oral infections. To manage her condition, the gastroenterologists included methotrexate (25 mg) in her regimen to reduce the immunogenicity of infliximab and minimize corticosteroid use, as the patient was in remission for Crohn's disease, and the oral PV lesions were under control. CONCLUSION: Young patients with Crohn's disease should be referred to an oral medicine specialist for comorbidity investigation, as oral PV and opportunistic infections can arise during immunosuppressive therapy. The use of TNF-alpha inhibitors in patients treated for inflammatory bowel disease, such as Crohn's, should be carefully evaluated for potential side effects, including oral PV.

Infliximab serum concentrations and disease activity in perianal fistulizing Crohn's disease: a cross-sectional study.

INTRODUCTION: Several studies associate the presence of higher serum concentrations of infliximab (IFX) with fistula healing in perianal Crohn's disease (CD). This study aimed to evaluate serum IFX concentrations in patients with perianal fistulizing CD (PFCD) in the presence or absence of general, clinical, and radiological activities. METHODS: This was a cross-sectional study in patients with PFCD during maintenance treatment with IFX from two centers. Serum IFX concentrations were measured before their next infusion and anal fistulas were evaluated by clinical examination and magnetic resonance imaging (MRI), whenever possible, performed 90 days before or after serum collection. According to clinical scores, radiological activity, and disease markers, patients were classified as in remission or active disease. Mean serum IFX concentrations were compared between the groups. RESULTS: Thirty-eight patients with PFCD were included. Demographic characteristics were similar in patients with remission or active disease. The overall mean serum IFX concentration of the entire sample (n = 38) was 5.21 ± 4.75 µg/mL (median 3.63; IQR 1.44-8.82). Serum IFX levels were 6.25 ± 5.34 µg/mL (median 3.62; IQR 1.95-11.03) in the 23 (60.5%) patients in remission and 3.63 ± 3.24 µg/mL (median 3.63; IQR 1.32-6.43; p = 0.226) in the 15 (39 .5%) who presented active disease. When evaluating general, clinical, and radiological activity of PFCD, and deep remission in isolation, no statistical difference between the groups was observed (p = 0.226, p = 0.418, p = 0.126, and p = 0.232, respectively). The 13 (34.2%) patients with an optimized dose of IFX had significantly higher serum concentrations than the remaining 25 (65.8%) with a standard dose: 8.33 ± 4.41 µg/mL (median 8.36; IQR 3.82-11.20) vs. 3.59 ± 4.13 µg/mL (median 1.97; IQR 1.18-3.85) -p = 0.002. Patients in remission and with an optimized IFX dose had significantly higher serum IFX concentrations than those with a standard dose (p = 0.006), whereas no significant difference was observed among those with active disease (p = 0.083). CONCLUSION: There were no differences in IFX serum concentrations in patients with clinical or radiological active PFCD as compared with those in remission. Patients with an optimized IFX dose had significantly higher serum concentrations than those with a standard dose. Patients in remission and with an optimized IFX dose had significantly higher serum concentrations than those with a standard dose.

Dietary Profile of Patients with Inflammatory Bowel Disease in Clinical Remission-A Preliminary Study.

Imbalanced dietary intake is associated with the development of inflammatory bowel diseases (IBDs) and is often observed during the active phases of Crohn's disease (CD) and ulcerative colitis (UC). Cumulative data also suggest the potential for dietary manipulation in avoiding IBD relapse. However, there is a paucity of dietary data from patients in clinical remission to guide such an approach. Our study aimed to characterize the dietary pattern and adequacy of patients with IBD in clinical remission. Data on dietary intake (three alternate 24 h food records) were collected from 40 patients with IBD (20 CD and 20 UC) and 45 gender-matched healthy controls (HC). Statistical comparisons between patients and controls employed Student's t-test, Mann-Whitney U, chi-squared, and Fisher's exact tests. The adequacy of dietary intake of IBD patients was further studied by assessing the nutrient inadequacy prevalence, estimated using the Dietary Reference Intakes (DRI) framework and the Estimated Average Requirement (EAR) parameter. We observed significant dietary imbalances among patients with IBD compared to the HC group, marked by disparities in both macronutrient and micronutrient intakes. Inadequacies with frequencies >80% were observed for the ingestion of total fiber and 13 micronutrients in IBD patients. Our preliminary findings suggest that imbalanced dietary intake is also characteristic among individuals with IBD during clinical remission, corroborating the need for dietary interventions in this population.

Effect of Curcumin Plus Piperine on Redox Imbalance, Fecal Calprotectin and Cytokine Levels in Inflammatory Bowel Disease Patients: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

The development and course of inflammatory bowel disease (IBD) are significantly influenced by inflammation and oxidative stress. Antioxidant therapy is a promising therapeutic option to enhance the clinical results of these individuals in this particular scenario. The purpose of this study is to assess the impact of curcumin, with or without piperine, on cytokines, fecal calprotectin (CalF), and oxidative stress enzymatic and non-enzymatic indicators in patients with IBD. METHODS: Patients with Crohn's disease (CD) or ulcerative colitis (UC) who were at least 18 years old and had intact liver and kidney function participated in this randomized, double-blind trial (trial registration: ensaiosclinicos.gov.br as RBR-89q4ydz). For 12 weeks, participants were randomly assigned to one of three groups: placebo, curcumin (1000 mg/day), or curcumin plus piperine (1000 mg + 10 mg/day). In order to examine oxidative stress indicators, CalF, and pro-inflammatory cytokines, blood and fecal samples were obtained, both prior to and following the intervention time. RESULTS: After adjusting for age, sex, and type of IBD, the curcumin plus piperine group had substantially higher serum levels of superoxide dismutase (SOD) than the placebo group (4346.9 ± 879.0 vs. 3614.5 ± 731.5; p = 0.041). There were no discernible variations between the groups in CalF, inflammatory markers, or other indicators of oxidative stress. CONCLUSIONS: In patients with inflammatory bowel disease (IBD), our study indicates that a 12-week curcumin plus piperine treatment effectively increases enzymatic antioxidant defense, especially SOD. These results demonstrate the potential therapeutic benefits of managing redox imbalance in individuals with IBD.

After Surgically Induced Remission, Ileal and Colonic Mucosa-Associated Microbiota Predicts Crohn's Disease Recurrence.

BACKGROUND & AIMS: Investigating the tissue-associated microbiota after surgically induced remission may help to understand the mechanisms initiating intestinal inflammation in Crohn's disease. METHODS: Patients with Crohn's disease undergoing ileocolic resection were prospectively recruited in 6 academic centers. Biopsy samples from the neoterminal ileum, colon, and rectosigmoid were obtained from colonoscopies performed after surgery. Microbial DNA was extracted for 16S rRNA gene sequencing. Microbial diversity and taxonomic differential relative abundance were analyzed. A random forest model was applied to analyze the performance of clinical and microbial features to predict recurrence. A Rutgeerts score ≥i2 was deemed as endoscopic recurrence. RESULTS: A total of 349 postoperative colonoscopies and 944 biopsy samples from 262 patients with Crohn's disease were analyzed. Ileal inflammation accounted for most of the explained variance of the ileal and colonic mucosa-associated microbiota. Samples obtained from 97 patients who were in surgically induced remission at first postoperative colonoscopy who went on to develop endoscopic recurrence at second colonoscopy showed lower diversity and microbial deviations when compared with patients who remained in endoscopic remission. Depletion of genus Anaerostipes and increase of several genera from class Gammaproteobacteria at the 3 biopsy sites increase the risk of further recurrence. Gut microbiome was able to predict future recurrence better than clinical features. CONCLUSIONS: Ileal and colonic mucosa-associated microbiome deviations precede development of new-onset ileal inflammation after surgically induced remission and show good predictive performance for future recurrence. These findings suggest that targeted microbial modulation is a plausible modality to prevent postoperative Crohn's disease recurrence.

Distal Ileitis Caused by Diffuse Large B-Cell Lymphoma in an Elderly Patient From Honduras.

Primary gastrointestinal non-Hodgkin lymphoma, while rare, most often presents as diffuse large B-cell lymphoma located in the stomach or ileocecal region. Presenting symptoms include abdominal pain, gastrointestinal bleeding, weight loss, or obstructive symptoms. Imaging can reveal ileitis or obstruction. We report a case of a man from Honduras with latent tuberculosis and chronic hepatitis B who presented with features of Crohn's disease through clinical, radiologic, and endoscopic findings but was ultimately diagnosed with diffuse large B-cell lymphoma by histology. We emphasize the importance of maintaining a broad differential for ileitis and the importance of histologic sampling when evaluating ileitis.

Granulomatous Salpingo-oophoritis Secondary to Crohn's Disease.

Crohn's disease (CD) represents a subtype of inflammatory bowel disease and can affect any portion of the gastrointestinal tract, from the mouth to the anus, with the capacity to affect extraintestinal organs. Salpingo-oophoritis is an uncommon manifestation of CD. There is only a limited number of documented case reports. We present the case of a patient with ileocolonic CD and secondary granulomatous salpingo-oophoritis. We emphasize the significance of clinical suspicion and an interdisciplinary approach as crucial factors in ensuring the effective management of the case.

Contribution of Toxin-Antitoxin Systems to Adherent-Invasive E. coli Pathogenesis.

Pathobionts have been implicated in various chronic diseases, including Crohn's disease (CD), a multifactorial chronic inflammatory condition that primarily affects the gastrointestinal tract, causing inflammation and damage to the digestive system. While the exact cause of CD remains unclear, adherent-invasive Escherichia coli (AIEC) strains have emerged as key contributors to its pathogenesis. AIEC are characterized by their ability to adhere to and invade intestinal epithelial cells and survive and replicate inside macrophages. However, the mechanisms underlying the virulence and persistence of AIEC within their host remain the subject of intensive research. Toxin-antitoxin systems (TAs) play a potential role in AIEC pathogenesis and may be therapeutic targets. These systems generally consist of two components: a toxin harmful to the cell and an antitoxin that neutralizes the toxin's effects. They contribute to bacterial survival in adverse conditions and regulate bacterial growth and behavior, affecting various cellular processes in bacterial pathogens. This review focuses on the current information available to determine the roles of TAs in the pathogenicity of AIEC. Their contribution to the AIEC stress response, biofilm formation, phage inhibition, the maintenance of mobile genetic elements, and host lifestyles is discussed.

Transición en enfermedades inflamatorias intestinales: de la pediatría a la adultez / Transition in inflammatory bowel diseases: from childhood to adulthood

El 25% de los pacientes con Enfermedades Inflamatorias Intestinales (EII) se diagnostican antes de los 20 años. En la mayor parte de los centros del país se lleva a cabo la "transferencia" del paciente desde un centro de atención pediátrico a uno de adultos. La "transición" es un criterio de calidad con beneficios en el control de la EII reduciendo el número de recaídas, de hospitalizaciones y de cirugías. Por tal motivo hemos desarrollado un Programa Interdisciplinario de Transición entre dos hospitales de referencia nacional e internacional en EII. Materiales y métodos: Entre 1/2021 y 12/ 2022 se incorporaron 24 pacientes que ingresaron en 3 fases: Fase 1 Pacientes entre 14 y 16 años asistidos en el Hospital Garrahan (HG) con un abordaje interdisciplinario. Fase 2. A partir de los 17 años se realizaron 2 (dos) encuentros en el HG en conjunto con gastroenterólogos de adultos evaluando adherencia y autonomía y la Fase 3 llevada a cabo en el Hospital B. Udaondo (HBU) sólo con el equipo de adultos luego de 6 meses de realizada la transferencia evaluando adherencia al tratamiento, consultas a emergencias, internación y/o cirugías Resultados: Al inicio del Programa el 66% de los pacientes presentaban una actividad moderada a severa vs el 8% al finalizar la fase 3. Luego de la transferencia el 12,5% necesito ingreso a guardia e internación y un 8% tratamiento quirúrgico. El 83% de los pacientes continúan en seguimiento luego de 6 meses de haber sido transferidos (AU)

Twenty-five percent of patients with inflammatory bowel diseases (IBD) are diagnosed before the age of 20 years. In most centers in the country, the "transfer" of the patient from a pediatric to an adult care center is done. However, "transition" is a quality criterion with benefits in the control of IBD by reducing the number of relapses, hospitalizations, and surgeries. For this reason, we developed an Interdisciplinary Transition Program between two national and international reference hospitals in IBD. Materials and Methods: Between January 2021 and December 2022, we incorporated 24 patients into a three-phase program. Phase 1 involved patients between 14 and 16 years of age seen at Garrahan Hospital (HG) with an interdisciplinary approach. Phase 2 began from 17 years of age, with two meetings held at HG involving adult gastroenterologists to evaluate adherence and autonomy. Phase 3 was conducted at Hospital B. Udaondo (HBU) only with the adult team, six months after the transfer, evaluating adherence to treatment, emergency consultations, hospitalizations, and/or surgeries. Results: At the beginning of the program, 66% of the patients presented with moderate to severe disease activity, compared to 8% at the end of Phase 3. After the transfer, 12.5% of the patients required emergency department visits and hospitalization, and 8% required surgical treatment. Eighty-three percent of the patients continue in the program and are still being followed up six months after the transfer (AU)

Is religiosity/spirituality in patients with Crohn's disease important to their quality of life?

The authors aim to study Religiosity/Spirituality (R/S) and Quality of Life (QoL) in patients with Crohn's disease and their correlation with the disease phenotypes. METHODS: Prospective cross-sectional cohort study with 151 consecutive patients enrolled from March 2021 to October 2021 at the Colorectal IBD Outpatient of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HCFMUSP). Sociodemographic, Religiosity/Spirituality (Duke University Religion Index - Durel) questionnaires and QoL (Inflammatory Bowel Disease Questionnaire - Short IBDQ-S) were applied. When necessary, qualitative variables were evaluated using the chi-square or Fisher's exact test. The Mann-Whitney and Kruskall-Wallis tests were used to analyze quantitative variables and compare more than two groups, both non-parametric statistical techniques. RESULTS: The most frequent location was Ileocolonic followed by Ileal and colonic (41.1 %, 27.2 %, and 25.2 %); only 6.6 % of subjects had a perianal presentation. Inflammatory, stenosing, and penetrating behaviors showed 36.4 %, 19.1 %, and 44.4 % respectively. The majority of the population is Catholic, Evangelical, or Spiritualist (92.4 %). QoL score showed no significant difference in the phenotypes. The scores for DUREL domains were 61.4 % for organizational religiosity, 75 % for non-organizational religiosity, 98.6 %, 93.6 % and 89.3 % for intrinsic spirituality, with high results in all disease phenotypes. CONCLUSIONS: The studied population presented homogeneous sociodemographic results and high religious and spiritual activity. R/S in a positive context were not associated with better QoL or phenotype. R/S is present in the patients' lives and could be seen as an important tool for adherence to treatment and the professional relationship between doctor and patient. The homogeneity of the sample difficult for an appropriate evaluation, which leads us to suggest new studies with more heterogeneous groups.

Patients with Inflammatory Bowel Disease who regularly consume fruits and vegetables present lower prevalence of disease activation: A cross-sectional study.

BACKGROUND: Exclusion diets are common practices among individuals with Inflammatory Bowel Disease (IBD). Reports that certain foods trigger or worsen symptoms are recurrent but lack evidence. The aim of the study was to identify which foods were most frequently avoided by patients with Crohn's Disease (CD) and Ulcerative Colitis (UC) and whether the consumption of any food group was associated with disease activity. METHODS: Cross-sectional study with adult patients seen at an outpatient clinic in a tertiary public hospital. Dietary intake and eating habits were accessed through questionnaires administered via telephone interview. Disease activity and symptoms were assessed using the Harvey-Bradshaw Index (IHB) for CD and the Lichtiger Index (LI) for UC. Poisson regression with a robust variance estimator was used to estimate prevalence ratios. Analyzes were performed using SPSS - Statistical Package for the Social Sciences. RESULTS: The study included 145 patients. Of these, 69.7% avoided certain foods, with citrus fruits and raw vegetables among the most avoided (16.8% and 13.8%, respectively). Regular consumption of fruits (PR = 0.56; CI 95% 0.32-0.97; p = 0.042) and vegetables (PR = 0.56; CI 95% 0.32-0.98; p = 0.045) was associated with a 44% lower prevalence of the active phase of the disease, compared to those who do not consume these foods, adjusted for age, sex and type of disease. Other food items did not present significant associations in the adjusted model. CONCLUSIONS: Fruit and vegetable intake appears to have a protective role in the recurrence of IBD. Excluding foods is a common practice, even among patients in remission, and this should be combated as it can lead to nutritional losses. It is important to reinforce with patients the benefits of a varied and less restrictive diet.

First Mexican Consensus on Crohn's disease.

INTRODUCTION: Crohn's disease (CD) is a subtype of chronic and incurable inflammatory bowel disease. It can affect the entire gastrointestinal tract and its etiology is unknown. OBJECTIVE: The aim of this consensus was to establish the most relevant aspects related to definitions, diagnosis, follow-up, medical treatment, and surgical treatment of Crohn's disease in Mexico. MATERIAL AND METHODS: Mexican specialists in the areas of gastroenterology and inflammatory bowel disease were summoned. The consensus was divided into five modules, with 69 statements. Applying the Delphi panel method, the pre-meeting questions were sent to the participants, to be edited and weighted. At the face-to-face meeting, all the selected articles were shown, underlining their level of clinical evidence; all the statements were discussed, and a final vote was carried out, determining the percentage of agreement for each statement. RESULTS: The first Mexican consensus on Crohn's disease was produced, in which recommendations for definitions, classifications, diagnostic aspects, follow-up, medical treatment, and surgical treatment were established. CONCLUSIONS: Updated recommendations are provided that focus on definitions, classifications, diagnostic criteria, follow-up, and guidelines for conventional medical treatment, biologic therapy, and small molecule treatment, as well as surgical management.

MicroRNAs in inflammatory bowel disease: What do we know and what can we expect?

MicroRNAs (miRNAs), small non-coding RNAs composed of 18-24 nucleotides, are potent regulators of gene expression, contributing to the regulation of more than 30% of protein-coding genes. Considering that miRNAs are regulators of inflammatory pathways and the differentiation of intestinal epithelial cells, there is an interest in exploring their importance in inflammatory bowel disease (IBD). IBD is a chronic and multifactorial disease of the gastrointestinal tract; the main forms are Crohn's disease and ulcerative colitis. Several studies have investigated the dysregulated expression of miRNAs in IBD, demonstrating their important roles as regulators and potential biomarkers of this disease. This editorial presents what is known and what is expected regarding miRNAs in IBD. Although the important regulatory roles of miRNAs in IBD are clearly established, biomarkers for IBD that can be applied in clinical practice are lacking, emphasizing the importance of further studies. Discoveries regarding the influence of miRNAs on the inflammatory process and the exploration of their role in gene regulation are expected to provide a basis for the use of miRNAs not only as potent biomarkers in IBD but also as therapeutic targets for the control of inflammatory processes in personalized medicine.

Interaction between diet and genetics in patients with inflammatory bowel disease.

In this editorial, we comment on the article by Marangoni et al, published in the recent issue of the World Journal of Gastroenterology 2023; 29: 5618-5629, about "Diet as an epigenetic factor in inflammatory bowel disease". The authors emphasized the role of diet, especially the interaction with genetics, in promoting the inflammatory process in inflammatory bowel disease (IBD) patients, focusing on DNA methylation, histone modifications, and the influence of microRNAs. In this editorial, we explore the interaction between genetics, gut microbiota, and diet, in an only way. Furthermore, we provided dietary recommendations for patients with IBD. The Western diet, characterized by a low fiber content and deficiency the micronutrients, impacts short-chain fatty acids production and may be related to the pathogenesis of IBD. On the other hand, the consumption of the Mediterranean diet and dietary fibers are associated with reduced risk of IBD flares, particularly in Crohn's disease (CD) patients. According to the dietary guidance from the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD), the regular consumption of fruits and vegetables while reducing the consumption of saturated, trans, dairy fat, additives, processed foods rich in maltodextrins, and artificial sweeteners containing sucralose or saccharine is recommended to CD patients. For patients with ulcerative colitis, the IOIBD recommends the increased intake of natural sources of omega-3 fatty acids and follows the same restrictive recommendations aimed at CD patients, with the possible inclusion of red meats. In conclusion, IBD is a complex and heterogeneous disease, and future studies are needed to elucidate the influence of epigenetics on diet and microbiota in IBD patients.

Atopic Dermatitis in Early Childhood and Risk of Inflammatory Bowel Disease: A Scandinavian Birth Cohort Study.

OBJECTIVE: To examine the association between early-life atopic manifestations and later risk of inflammatory bowel disease (IBD), for which prospective data are scarce. STUDY DESIGN: The population-based All Babies in Southeast Sweden (ABIS) and Norwegian Mother, Father, and Child (MoBa) cohorts follow children from birth (ABIS 1997-1999; MoBa 2000-2009) to the end of 2021. Based on validated questionnaires, parents prospectively reported information on asthma, food-related allergic symptoms, atopic dermatitis, and allergic rhinitis by age 3. IBD was defined by ≥ 2 diagnostic records in the national health registries. Cox regression estimated hazard ratios adjusted (aHRs) for parental IBD, atopy, education level, smoking habits, and national origin. Cohort-specific estimates were pooled using a random-effects model. RESULTS: We compiled data on 83 311 children (ABIS, n = 9041; MoBa, n = 74 270). In over 1 174 756 person-years of follow-up, 301 participants were diagnosed with IBD. Children with atopic dermatitis at age 3 had an increased risk of IBD (pooled aHR = 1.46 [95% CI = 1.13-1.88]), Crohn's disease (pooled aHR = 1.53 [95%CI = 1.04-2.26]), and ulcerative colitis (pooled aHR = 1.78 [95%CI = 1.15-2.75]). Conversely, any atopic manifestation by age 3 was not associated with IBD (pooled aHR = 1.20 [95%CI = 0.95-1.52]), nor were analyses specifically focused on early-life food-related allergic symptoms, asthma, and allergic rhinitis. CONCLUSION: While atopic manifestations in early childhood were overall not associated with IBD, children with atopic dermatitis specifically were at increased risk of developing IBD, suggesting shared etiologic traits; these findings might be useful in identifying at-risk individuals for IBD.

Leukocyte dysfunction and reduced CTLA-4 expression are associated with perianal Crohn's disease.

Although perianal Crohn's disease (PCD) is highly associated with the exacerbated inflammation, the molecular basis and immunological signature that distinguish patients who present a history of perianal lesions are still unclear. This paper aims to define immunological characteristics related to PCD. In this cross-sectional observational study, we enrolled 20 healthy controls and 39 CD patients. Blood samples were obtained for the detection of plasma cytokines and lipopolysaccharides (LPS). Peripheral blood mononuclear cells (PBMCs) were phenotyped by flow cytometry. Leukocytes were stimulated with LPS or anti-CD3/anti-CD28 antibodies. Our results show that CD patients had augmented plasma interleukin (IL)-6 and LPS. However, their PBMC was characterized by decreased IL-6 production, while patients with a history of PCD produced higher IL-6, IL-8, and interferon-γ, along with decreased tumor necrosis factor alpha (TNF). CD patients had augmented FoxP3 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulatory markers, though the PCD subjects presented a significant reduction in CTLA-4 expression. CTLA-4 as well as IL-6 and TNF responses were able to distinguish the PCD patients from those who did not present perianal complications. In conclusion, IL-6, TNF, and CTLA-4 exhibit a distinct expression pattern in CD patients with a history of PCD, regardless of disease activity. These findings clarify some mechanisms involved in the development of the perianal manifestations and may have a great impact on the disease management.

microRNA-mRNA Networks Linked to Inflammation and Immune System Regulation in Inflammatory Bowel Disease.

The molecular processes linked to the development and progression of Crohn's disease (CD) and ulcerative colitis (UC) are not completely understood. MicroRNAs (miRNAs) regulate gene expression and are indicated as diagnostic, prognostic, and predictive biomarkers in chronic degenerative diseases. Our objectives included the identification of global miRNA expression in CD and UC, as well as miRNA target genes, miRNA-mRNA interaction networks, and biological functions associated with these different forms of inflammatory bowel disease (IBD). METHODS: By performing a comprehensive meta-analysis, we integrated miRNA expression data from nine studies in IBD. We obtained detailed information on significantly deregulated miRNAs (fold change, FC ≥ 2 and p < 0.05), sample type and number, and platform applied for analysis in the training and validation sets. Further bioinformatic analyses were performed to identify miRNA target genes, by using the microRNA Data Integration Portal tool. We also sought to identify statistically enriched pathways of genes regulated by miRNAs using ToppGene Suite. Additional analyses were performed to filter for genes expressed in intestinal tissue using the European Bioinformatics Institute (EBI) database. RESULTS: Our findings showed the upregulation of 15 miRNAs in CD and 33 in UC. Conversely, six miRNAs were downregulated in CD, while seven were downregulated in UC. These results indicate a greater deregulation of miRNAs in UC compared to CD. Of note, miRNA target genes were enriched for immune system regulation pathways. Among significantly deregulated miRNAs with a higher number of miRNA-target gene interactions, we identified miR-199a-5p and miR-362-3p altered in CD, while among UC case patients, miRNA-target gene interactions were higher for miR-155-5p. CONCLUSIONS: The identified miRNAs play roles in regulating genes associated with immune system regulation and inflammation in IBD. Such miRNAs and their target genes have the potential to serve as clinically relevant biomarkers. These findings hold promise for enhancing the accuracy of diagnoses and facilitating the development of personalized treatment strategies for individuals with various forms of IBD.

Clinical factors associated with severity in patients with inflammatory bowel disease in Brazil based on 2-year national registry data from GEDIIB.

The Brazilian Organization for Crohn's Disease and Colitis (GEDIIB) established a national registry of inflammatory bowel disease (IBD). The aim of the study was to identify clinical factors associated with disease severity in IBD patients in Brazil. A population-based risk model aimed at stratifying the severity of IBD based on previous hospitalization, use of biologics, and need for surgery for ulcerative colitis (UC) and Crohn's Disease (CD) and on previous complications for CD. A total of 1179 patients (34.4 ± 14.7y; females 59%) were included: 46.6% with UC, 44.2% with CD, and 0.9% with unclassified IBD (IBD-U). The time from the beginning of the symptoms to diagnosis was 3.85y. In CD, 41.2% of patients presented with ileocolic disease, 32% inflammatory behavior, and 15.5% perianal disease. In UC, 46.3% presented with extensive colitis. Regarding treatment, 68.1%, 67%, and 47.6% received biological therapy, salicylates and immunosuppressors, respectively. Severe disease was associated with the presence of extensive colitis, EIM, male, comorbidities, and familial history of colorectal cancer in patients with UC. The presence of Montreal B2 and B3 behaviors, colonic location, and EIM were associated with CD severity. In conclusion, disease severity was associated with younger age, greater disease extent, and the presence of rheumatic EIM.