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Background: Inflammatory bowel disease (IBD) is a chronic, systemic condition affecting the gastrointestinal tract. IBD can be severe and are associated with impairment in growth, school absences, abdominal pain, and fatigue. Physical activity (PA) could have an anti-inflammatory effect in addition to other benefits. It is important to address the possible risks, physiological effects of PA, and potential barriers, and facilitators for PA participation in pediatric IBD. However, potential barriers and facilitators to PA have yet to be adequately described. Methods: We conducted a scoping review to map and describe the current literature on PA in pediatric IBD populations between 1980 and April 2022 using Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines for Scoping reviews. Results: Nineteen articles were identified including 10 descriptive, 6 interventional, and 3 physiological responses to PA studies. Patients and healthy controls demonstrated similar responses to exercise. Barriers to participation were low self-esteem, body image, and active IBD symptoms. Facilitators included personal interest, activity with friends, and support from family. Conclusion: This review highlighted that PA participation may reduce in children with IBD-related symptoms. Short- and medium-term impacts of PA on immune modulation require further study; it is possible that regular PA does not negatively affect biomarkers of disease activity. [ABSTRACT FROM AUTHOR]

Background: Our previous study has demonstrated a decreased colonic CD8+CD39+ T cells, enrichment of granzyme A (GZMA), was found in pediatric-onset colitis and inflammatory bowel disease (IBD) characterized by impaired intestinal barrier function. However, the influence of GZMA on intestinal barrier function remains unknown. Methods: Western blotting(WB), real-time PCR (qPCR), immunofluorescence (IF) and in vitro permeability assay combined with intestinal organoid culture were used to detect the effect of GZMA on intestinal epithelial barrier function in vivo and in vitro. Luciferase, immunoprecipitation (IP) and subcellular fractionation isolation were performed to identify the mechanism through which GZMA modulated intestinal epithelial barrier function. Results: Herein, we, for the first time, demonstrated that CD8+CD39+ T cells promoted intestinal epithelial barrier function through GZMA, leading to induce Occludin(OCLN) and Zonula Occludens-1(ZO-1) expression, which was attributed to enhanced CDX2-mediated cell differentiation caused by increased glutathione peroxidase 4(GPX4)-induced ferroptosis inhibition in vivo and in vitro. Mechanically, GZMA inhibited intestinal epithelial cellular PDE4B activation to trigger cAMP/PKA/CREB cascade signaling to increase CREB nuclear translocation, initiating GPX4 transactivity. In addition, endogenous PKA interacted with CREB, and this interaction was enhanced in response to GZMA. Most importantly, administration of GZMA could alleviate DSS-induced colitis in vivo. Conclusion: These findings extended the novel insight of GZMA contributed to intestinal epithelial cell differentiation to improve barrier function, and enhacement of GZMA could be a promising strategy to patients with IBD. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is an idiopathic and heterogeneous large intestine disease, characterized by chronic mucosa and submucosa inflammation. Alteration of the intestinal microbiome in UC may be responsible for modifications in metabolite production. Aim: To investigate the microbiota status and trimethylamine-N-oxide (TMAO) metabolite levels in patients with UC according to clinical and endoscopic activity. Methods: As part of a grant project AP14871959 from September 2022 to October 2023, 31 patients with UC and 15 healthy volunteers over 18 years at the Clinic of NCJSC "KMU" were assessed for blood TMAO level and metagenomic sequencing of fecal microbiome. Results: A significant depletion of the main representatives of Bacteroides, Parabacteroides, Prevotella; and an increase in the relative abundance of the genera Actinomyces, Klebsiella, Limosilactobacillus, Streptococcus, Escherichia-Shigella were detected in patients with UC. The number of p_Actinobacteria (g_Collinsella) and p_Eubacterium (g_Xylanophilum) representatives with genes encoding TMA-trimethylamine conversion is significantly reduced in UC patients. TMAO levels were significantly lower in UC patients than in healthy individuals (0.233 µmol/L, p = 0.004). TMAO decreased with disease severity and significantly differed between patients with different activities (p = 0.034). Conclusions: The composition of the intestinal microbiome changes and the level of TMAO decreases in patients with UC at different activities. [ABSTRACT FROM AUTHOR]

Fibrosis is an important pathological change in inflammatory bowel disease (IBD), but the mechanism has yet to be elucidated. WNT2B high‑expressed fibroblasts are enriched in IBD intestinal tissues, although the precise function of this group of fibroblasts remains unclear. This study investigated whether WNT2B high‑expressed fibroblasts aggravated intestinal tissue damage and fibrosis. Our study provides evidence that WNT2B high‑expressed fibroblasts and NK cells were enriched in colitis tissue of patients with IBD. WNT2B high‑expressed fibroblasts secreted wnt2b, which bound to FZD4 on NK cells and activated the NF-κB and STAT3 pathways to enhance IL-33 expression. TCF4, a downstream component of the WNT/β-catenin pathway, bound to p65 and promoted binding to IL-33 promoter. Furthermore, Salinomycin, an inhibitor of the WNT/β-catenin pathway, inhibited IL-33 secretion in colitis, thereby reducing intestinal inflammation.Knocking down WNT2B reduces NK cell infiltration and IL-33 secretion in colitis, and reduce intestinal inflammation and fibrosis. In conclusion, WNT2B high‑expressed fibroblasts activate NK cells by secreting wnt2b, which activates the WNT/β-catenin and NF-κB pathways to promote IL-33 expression and secretion, potentially culminating in the induction of colonic fibrosis in IBD. Key messages: WNT2B high-expressed fibroblasts and NK cells are enriched in colitis tissue, promoting NK cells secreting IL-33. Wnt2b activates NF-κB and STAT3 pathways promotes IL-33 expression by activating p65 and not STAT3. syndrome TCF4 binds to p65 and upregulates the NF- κB pathway. Salinomycin reduces NK cell infiltration and IL-33 secretion in colitis. Knocking down WNT2B mitigates inflammation and fibrosis in chronic colitis. [ABSTRACT FROM AUTHOR]

The escalating worldwide prevalence of Crohn's disease (CD) among children and adolescents, coupled with a trend toward earlier onset, presents significant challenges for healthcare systems. Moreover, the chronicity of this condition imposes substantial individual burdens. Consequently, the principal objective of CD treatment revolves around rapid inducing remission. This study scrutinizes the impact of age, gender, initial disease localization, and therapy on the duration to achieve disease activity amelioration. Data from the Saxon Pediatric IBD Registry in Germany were analyzed over a period of 15 years. In addition to descriptive methods, logistic and linear regression analyses were conducted to identify correlations. Furthermore, survival analyses and Cox regressions were utilized to identify factors influencing the time to improvement in disease activity. These effects were expressed as Hazard Ratios (HR) with 95% confidence intervals. Data on the clinical course of 338 children and adolescents with CD were available in the registry. The analyses showed a significant correlation between a young age of onset and the severity of disease activity. It was evident that treatment with anti-TNF (Infliximab) was associated with a more favorable prognosis in terms of the time required for improvement in disease activity. Similarly, favorable outcomes were observed with the combination therapies of infliximab with enteral nutrition therapy and Infliximab with immunosuppressants. Conclusion: Our analysis of data from the Saxon Pediatric IBD Registry revealed that the timeframe for improvement of disease activity in pediatric Crohn's disease is influenced by several factors. Specifically, patient age, treatment modality, and initial site of inflammation were found to be significant factors. The study provides important findings that underline the need for individualized treatment. [ABSTRACT FROM AUTHOR]

There has been an increased ability to investigate the human microbiota through next-generation sequencing and functional assessment. This advancement has rapidly expanded our ability to study and manipulate the gastrointestinal microbiome to mitigate disease. Fecal microbiota transplantation, a therapy that broadly transfers the entire intestinal ecosystem, has been explored as a potential therapeutic in a variety of gastrointestinal, hepatic, and extraintestinal conditions. The field, however, continues to evolve, with a movement toward precision microbiome therapeutics, individualizing care for various disorders. This review will describe the use of fecal microbiota transplantation, microbiota restoration, and precision microbiome therapeutics, focusing on gastrointestinal and hepatic diseases. [ABSTRACT FROM AUTHOR]

Background: Cathepsins, key regulators of the pathology of gastrointestinal disorders such as inflammatory bowel disease (IBD), are a target protease that has attracted much attention in recent years. IBD is a chronic and relapsing inflammatory disorder of the gut. Traditional studies have shown a correlation between cathepsin and the risk of IBD, while the causal relationship remains unclear. Methods: This study utilized Mendelian randomization techniques to evaluate the causal relationships between eleven cathepsins and the subtypes of IBD, such as ulcerative colitis (UC) and Crohn's disease (CD). We also performed a series of sensitivity analyses to validate the primary Mendelian randomization (MR) results, including Cochran's Q test, the MR-PRESSO global test, and the MR pleiotropy test. Results: The forward MR analyses showed no significant association between cathepsins and IBD. Reverse Mendelian randomization analyses suggested that UC might lead to elevated cathepsin G levels [inverse-variance weighted (IVW): p = 0.038, b = 9.966], and CD might cause a decrease in cathepsin B levels [IVW: p = 0.002, b = -10.525] and cathepsin L1 levels [IVW: p = 0.045, b = -4.742]. Conclusions: Our findings offer novel and comprehensive evidence on the impact of UC or CD on cathepsins, potentially providing valuable insights into the treatment and prognosis of IBD. [ABSTRACT FROM AUTHOR]

Objective: This study aims to explore the causal relationship between cholecystectomy and inflammatory bowel disease (IBD)/irritable bowel syndrome (IBS) and the role of serum bile acids and gut microbiota in this context. Methods: Utilizing genetic variant data from previous Genome-Wide Association Studies (GWAS), this study employed a two-sample MR approach to assess the causal effect of cholecystectomy on IBD/IBS. Results: The MR analysis suggested a potential negative causal relationship between cholecystectomy and UC (p = 0.0233, OR 0.9773, 95%CI 0.9581–0.9969) and a positive causal relationship between cholecystectomy and IBS (p = 0.0395, OR 4.077, 95%CI 1.0699–15.5362). Various sensitivity analyses reinforced the reliability of the causal relationship. However, the analysis did not find definitive results between serum bile acids or gut microbiota and cholecystectomy or IBD/IBS, possibly due to insufficient statistical power. MVMR find a causal relationship between bile acids and IBS (p = 0.0015, b = 0.4085) and UC (p = 0.0198, b = 0.0029). Conclusion: This study provides evidence of a causal relationship between cholecystectomy and IBD/IBS, highlighting the potential risk reduction for UC and increased risk for IBS following cholecystectomy. The role of bile acids and gut microbiota in this relationship remains unclear, necessitating further research to validate the causality and explore underlying mechanisms. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic disorder associated with inflammation in the gastrointestinal tract, leading to a range of debilitating symptoms. Fecal calprotectin is an established biomarker for ulcerative colitis (UC), one of the main IBD diseases, which provides indications of the presence and severity of inflammation in the digestive tract. Enzyme‐Linked Immunosorbent Assay (ELISA) as a gold standard approach for fecal calprotectin detection is time‐consuming and impractical in point‐of‐care settings. Moreover, obtaining fecal samples from patients is challenging and inhibits longitudinal monitoring. To address these specific problems, we have developed a novel approach for detecting calprotectin which leverages clustered regularly interspaced short palindromic repeats (CRISPR)/Cas technology. We successfully developed a portable tube‐based CRISPR/Cas assay for point‐of‐care testing of calprotectin. This assay showed a detection range from 1 to 10,000 ng/ml (over 4 log units), using both fluorescent and colorimetric analytical techniques. The established assay was further validated through measurements in mucosal samples obtained in an anesthetised preclinical rodent model of UC, with 2–3 times higher calprotectin concentration detected in UC rat samples compared to that of healthy control animals. This point‐of‐care test may provide a rapid, precise, and user‐friendly approach for the diagnosis and monitoring of IBD through mucosal sample testing. [ABSTRACT FROM AUTHOR]

Background: Standardized clinical care processes for patients with Crohn's disease (CD) and a permanent ileostomy (PI) are lacking. The EndOTrial consortium aims to address this gap by developing pathways for care. Methods: In this umbrella review, we searched major databases for relevant systematic reviews (SRs) or scoping reviews (ScR) published until January 5, 2024. Screening, data extraction, and quality appraisal (AMSTAR 2) were performed by two independent reviewers. Results: Of 1349 screened papers, 22 reviews met our inclusion criteria, including 20 SRs (eight with meta-analysis) and 2 ScRs. None exclusively focused on PI. Furthermore, nine reviews did not mention patients with inflammatory bowel disease (IBD), and only two reviews included patients with high-output ileostomy, highlighting a large evidence gap. The identified reviews covered six categories with nine types of interventions, including ostomy care pathways, peristomal skin care, patient education, clinical management of high-output stoma, management and prevention of postoperative ileus, dietary and nutritional support, nursing and supporting care, telemedicine, and self-management interventions. Most SRs including nursing interventions for stoma care highlighted nurses' role in a variety of standard and specialized treatments. Notably, none of the reviews exclusively examined disease recurrence, stoma pouching systems or adhesives, behavioral interventions, or mental health in patients living with ileostomy. Conclusions: Evidence for best practice interventions to treat complications and improve quality of life in patients living with an ileostomy for CD is limited and heterogeneous. These results outline the need for standardized clinical care processes and pathways tailored to the unique needs of this patient population. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Perianal draining tunnels in hidradenitis suppurativa (HS) and perianal fistulizing inflammatory bowel disease (IBD) present diagnostic and management dilemmas.We conducted a retrospective chart review of patients with perianal disease evaluated at Mayo Clinic from January 1, 1998, through July 31, 2021. Patients' demographic and clinical data were extracted, and 28 clinical features were collected. After experimenting with several machine learning techniques, random forests were used to select the 15 most important clinical features to construct the diagnostic prediction model to distinguish perianal HS from fistulizing perianal IBD.A total of 263 patients were included (98 with HS, 100 with IBD, and 65 with both IBD and HS). Patients with HS had a higher mean body mass index, a higher smoking rate, and more commonly showed cutaneous manifestations of tunnels and comedones, while fistulas, abscesses, induration, anal tags, ulcers, and anal fissures were more common in patients with IBD. In addition to having lesions in the perianal area, patients with IBD often had lesions in the buttocks and perineum, while those with HS had additional lesions in the axillae and groin. Among the statistically significant features, the 15 most important were identified by random forest: fistula, tunnel, digestive symptom, knife‐cut ulcer, perineum, body mass index, age, axilla, abscess, tags, smoking, groin, genital cutaneous edema, erythema, and bilateral/unilateral.The results of this study may help differentiate perianal lesions, especially perineal HS and fistulizing perineal IBD, and provide promise for a better therapeutic outcome. [ABSTRACT FROM AUTHOR]

Disrupted cholesterol homeostasis plays a critical role in the development of multiple diseases, such as cardiovascular disease and cancer. However, the role of cholesterol in inflammatory bowel disease (IBD) remains unclear. In the present study, we investigated whether and how high levels of cholesterol in the diet affect experimental colitis in mice. A normal diet supplemented with 1.25% cholesterol (high cholesterol diet) caused more severe colitis and aggravated the disruption of intestinal tight junction structure, accompanied by higher colonic tissue total cholesterol (TC) levels in a dextran sulfate sodium (DSS)‐induced experimental colitis mouse model. Cholesterol aggravated DSS‐induced intestinal epithelial barrier impairment and nuclear sterol regulatory element‐binding protein 2 (nSREBP2) inhibition both in vivo and in vitro. In addition, nSREBP2 overexpression ameliorated cholesterol‐induced intestinal epithelial barrier disruption in Caco2 cells. Interestingly, inhibition of SREBP2 disrupted intestinal epithelial barrier in the absence of cholesterol. Furthermore, SREBP2 regulated the protein expression of tight junction proteins (occludin/Zo‐1) via modulating caveolin‐1‐mediated endocytosis and lysosomal degradation. Analysis of UK Biobank data indicated that, in fully adjusted models, higher serum TC concentrations were an independent protective factor for IBD incidence. The sterol regulatory element‐binding factor 2 (SREBF2) gene rs2228313 (G/C) genetic variant was associated with the incidence of IBD and the CC genotype of SREBF2 rs2228313 was associated with higher serum TC levels and decreased the risk of IBD. In summary, a high cholesterol diet aggravates DSS‐induced colitis in mice by down‐regulating nSREBP2 expression, thereby promoting the endocytic degradation of tight junction proteins. In humans, SREBF2 gene single nucleotide polymorphism rs2228313 and serum TC levels are associated with IBD incidence. [ABSTRACT FROM AUTHOR]

Introduction: Psoriatic arthritis is a chronic disease involving peripheral arthritis, spondylitis, dactylitis (inflammation of the whole digit) and enthesitis. It is a disease equally prevalent in both genders. Psoriatic arthritis coexists with several conditions, including metabolic syndrome, obesity, cardiovascular disease, inflammatory bowel disease, and liver disease. The reciprocal effects of comorbidities with psoriatic arthritis are demonstrated by recent research. There are several risk factors associated with the condition that might hasten or worsen its symptoms. Aim of the Study: The purpose of this paper is to present a thorough analysis of the research that has been done on comorbidities and risk factors for psoriatic arthritis. With an emphasis on changeable elements that might impact the disease's progression, the goal is to illustrate the multifaceted nature of psoriatic arthritis. The intention is also to highlight comorbidities that need to be considered while treating a patient with the illness. Materials and methods: An analysis of papers available in PubMed and Google Scholar was performed using the following key words: psoriatic arthritis, psoriatic arthritis and lifestyle, psoriatic arthritis and comorbidities, psoriatic arthritis and cardiovascular risk, psoriatic arthritis and gastrointestinal diseases, psoriatic arthritis and physical activity, psoriatic arthritis and diet, psoriatic arthritis and alcohol, psoriatic arthritis and smoking. Conclusions: Psoriatic arthritis is a chronic disease that affects many areas of patients' lives. It is critical to consider the connections that exist between this illness and other comorbidities. In order to provide a patient with this ailment with the best care possible, variables that might exacerbate the illness's progression must also be taken into consideration. Patients' mental health should get particular attention, and lifestyle modifications should be promoted. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) is a chronic condition that significantly affects patients' physical, mental, and social health, as well as their overall quality of life. Effective management of the disease demands self-management skills, enabling patients to navigate the daily challenges associated with IBD, such as unpredictable flare-ups, frequent hospitalization, severe symptoms, pain, and physical changes. Objectives: This study examines the motivational aspects of self-management for patients with IBD and focuses on the role of autonomy and directive support from healthcare professionals in enhancing their self-concordance and self-efficacy. Design: From November 2022 to February 2023, a cross-sectional questionnaire study was conducted at the IBD Center of Internal Medicine Clinic in Szeged, Hungary. Methods: A total of 374 adult patients with IBD completed the paper–pencil questionnaire, of whom 241 patients (64.4%) had Crohn's disease, and 133 patients (35.6%) had ulcerative colitis. Results: Based on the findings of the path analysis (χ2 (8) = 18.914, p = 0.01, comparative fit index = 0.935, TLI = 0.837, root mean squared error of approximation = 0.06), autonomy support positively predicted self-concordance (β = 0.48) and self-efficacy (β = 0.02), particularly during disease relapse. In addition, self-concordance and self-efficacy predicted more positive (βs = 0.28 and 0.35) and fewer negative emotional experiences (βs = −0.09 and −0.20). The model's associations varied between the relapse and remission groups, indicating distinct impacts on different states of the disease. Conclusion: Overall, autonomy support from healthcare professionals has been shown to enhance self-management in patients with IBD, particularly during disease relapse. Meanwhile, self-concordance and self-efficacy act as positive internal factors, thus reducing negative emotional experiences, especially during remission. In sum, this study underscores the need for further exploration of the motivational aspects of self-management and provides insights into developing interventions that promote the health behaviors of patients with IBD. Plain language summary: Self-management of inflammatory bowel disease patients Autonomy support from healthcare professionals has been shown to significantly improve the effectiveness of self-management in patients with inflammatory bowel disease (IBD) (especially during disease relapse), by enhancing their self-concordance and self-efficacy. In this case, the interplay between disease activity, positive and negative emotions, and self-regulatory mechanisms underscores the importance of examining the motivational aspects for developing interventions that promote health behaviors in patients with IBD. [ABSTRACT FROM AUTHOR]

Subcutaneous infliximab is now approved and available in France based on a pivotal trial demonstrating its non-inferiority to its intravenous (IV) formulation according to a pharmacological endpoint. In France, the acceptance rate for the switch is around 75%. It seems important to ensure the absence of inflammatory activity by an objective tool to tailor the treatment before switching to SC infliximab. In patients treated at standard IV dose (5 mg/kg every 8 weeks) or 10 mg/kg every 8 weeks, the switch (at SC dose of 120 mg every 2 weeks) does not expose to an increased risk of relapse (13.7% to 21.2%). Patients treated at 10 mg/kg every 6 weeks had no increased risk of relapse (at 120 mg SC every 2 weeks) at 6 months compared to the standard dose (17.6% at 6 months), but a slight increase at 18 months (37.5%). On the other hand, the relapse rate was significantly higher at 120 mg SC every 2 weeks for patients at highly intensified doses (10 mg/kg every 4 weeks): 66.7% at 6 months and 92.9% at 18 months. However, the fact that the intensification of SC treatment at a dose of 240 mg every 2 weeks makes it possible to obtain clinical remission again in 93.3% of cases, associated with the fact that the treatment discontinuation rate for relapse is not increased in patients initially treated at 10 mg/kg every 4 weeks advocate for switching to intensified SC regimen (240 mg every 2 weeks or 120 mg every week) in these highly intensified patients. Patients suffering from obesity or with active or previous perianal lesions do not seem to have an increased risk of relapse after the switch. The clinical meaning of infliximab serum levels for a patient treated with SC infliximab is not the same as that in IV formulation, particularly in terms of thresholds and their interpretation. Intuitively and based on the design of real-life studies (REMSWITCH, PEREM), SC therapy should be started on the theoretical date of the next intravenous infusion. The data synthesized in this review confirm that the switch from IV to SC infliximab is well accepted, well tolerated and exposed to a low risk of relapse leading us to suggest a practical algorithm to guide IBD physicians in daily practice. [ABSTRACT FROM AUTHOR]

Background: Dogs with chronic inflammatory enteropathy (CIE) are typically classified into food‐responsive enteropathy (FRE), antibiotic‐responsive enteropathy (ARE), immunomodulator‐responsive enteropathy (IRE), and nonresponsive enteropathy (NRE) based on response to therapy(ies). Reassessment of initial categorization (especially IRE and NRE) is lacking. Objectives: Investigate validity of categorization scheme when reassessed at least 1 year after diagnosis. Animals: Sixty client‐owned dogs with CIE. Methods: Retrospective study. Clinical information was gathered from records and owners from time of diagnosis (TD), time of initial response (TIR), and at least 1 year after diagnosis (T≥1y). Category change was defined as a switch between groups. Results: Median disease activity index (CIBDAI) at TD was 9 and reduced significantly to 1 at T≥1y (P <.0001). At TIR, dogs were categorized as: FRE 27/60 (45%, 95% binomial confidence intervals [CI], 0.32‐0.58), IRE 30/60 (50%, CI 0.37‐0.63), ARE 0/60 (0%), NRE 3/60 (5%, CI −0.01 to 0.11). Seventeen of 27 (63%) FRE dogs had previously had at least 1 unsuccessful diet trial. At T≥1y, categorization changed to FRE 44/60 (73%, CI 0.62‐0.85), IRE 14/60 (23%, CI 0.13‐0.34), ARE 0/60 (0%), NRE 2/60 (3%, CI −0.01 to 0.08). Group changes were found for 24/60 (40%) dogs, largest change was from IRE to FRE (19/24, 79%). Immunosuppressive dosages were administered as sole treatment in 1/30 (3%) IRE dogs at TIR. Conclusions and Clinical Importance: Chronic inflammatory enteropathy categorization based on initial response to therapy needs reassessment after 1 year. Frequent change from IRE to FRE suggests that dogs initially categorized as IRE might have been initially categorized as FRE if multiple dietary trials had been performed. In our study, antibiotics were not needed to achieve satisfying clinical responses. [ABSTRACT FROM AUTHOR]

Background: Infectious bursal disease (IBD) is a viral infectious disease that affects young chicks. A cross‐sectional study was conducted from October 2020 to June 2021 to determine seroprevalence and associated risk factors of IBD on backyard chickens of purposively selected three districts of Buno Bedelle Zone, Southwestern Ethiopia. Methods: The study was carried out via a collection of serum samples, questionnaire surveys, and a total of 768 serum samples were collected from randomly selected backyard chickens of the study areas and examined for the presence of IBD virus. These serum samples were processed by using an indirect enzyme‐linked immunosorbent assay test procedure in laboratories. SPSS version 20 was used for data analysis and descriptive statics techniques were used. Results: Out of a total serum samples collected, 361 of them were found positive for the disease with an overall seroprevalence of 47%. Different seroprevalence rates of IBD with 55.9%, 43.3% and 41.2% were recorded in Didessa, Chora and Gechi districts, respectively. The result indicated that there was statistically significant difference (p < 0.05) of the disease among the three districts. Among the nine Peasant Associations (PAs) observed for seroprevalence of IBD, highest (62.9%) and lowest (34.20%) seroprevalence of the disease was recorded in Yembero and Shengela PAs, respectively. However, IBD was statistically significant in only Shengela PA of Chora district (p = 0.04, OR = 1.93 and 95% CI 1.04–3.58) and Seko PA of Gechi district (p = 0.05, OR = 1.79 and 95% CI 1.01–3.16). Even though sex, breed, age, source and management‐based seroprevalence was observed in the present study, the result indicated that there was only statistical significant difference (p = 0.004, OR = 0.62 and 95% CI 0.45–0.86) seen in which higher seroprevalence of IBD was determined in exotic (50.3%) than in local (38.6%) chickens breeds of the study areas. Conclusion: Generally, higher seroprevalence of IBD in the present study indicates a widely distribution of the disease and one of the potential threats for poultry production in the study areas. So, chicken vaccination and improved management system should be warranted in order to control the disease effectively. [ABSTRACT FROM AUTHOR]

Inflammatory Bowel Diseases (IBD), which encompass ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic inflammation and tissue damage of the gastrointestinal tract. This study aimed to uncover novel disease-gene signatures, dysregulated pathways, and the immune cell infiltration landscape of inflamed tissues. Eight publicly available transcriptomic datasets, including inflamed and non-inflamed tissues from CD and UC patients were analyzed. Common differentially expressed genes (DEGs) were identified through meta-analysis, revealing 180 DEGs. DEGs were implicated in leukocyte transendothelial migration, PI3K-Akt, chemokine, NOD-like receptors, TNF signaling pathways, and pathways in cancer. Protein–protein interaction network and cluster analysis identified 14 central IBD players, which were validated using eight external datasets. Disease module construction using the NeDRex platform identified nine out of 14 disease-associated genes (CYBB, RAC2, GNAI2, ITGA4, CYBA, NCF4, CPT1A, NCF2, and PCK1). Immune infiltration profile assessment revealed a significantly higher degree of infiltration of neutrophils, activated dendritic cells, plasma cells, mast cells (resting/activated), B cells (memory/naïve), regulatory T cells, and M0 and M1 macrophages in inflamed IBD tissue. Collectively, this study identified the immune infiltration profile and nine disease-associated genes as potential modulators of IBD pathogenesis, offering insights into disease molecular mechanisms, and highlighting potential disease modulators and immune cell dynamics. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic non-specific intestinal inflammatory disease that affects millions of people worldwide, and current treatment methods have certain limitations. This study aimed to explore the therapeutic potential and mechanism of action of lemairamin (Wgx-50) in inflammatory bowel disease (IBD). We used dextran sulfate sodium (DSS)-treated zebrafish as an inflammatory bowel disease model, and observed the effect of Wgx-50 on DSS-induced colitis inflammation. The results of the study showed that Wgx-50 could reduce the expression of pro-inflammatory cytokines induced by DSS and inhibit the recruitment of neutrophils to the site of intestinal injury. Further experiments revealed that Wgx-50 exerted its anti-inflammatory effect by regulating the activation of the Akt pathway. These research findings indicate that Wgx-50 possesses anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

Aims: Use of infliximab (IFX) has improved outcomes in children with inflammatory bowel disease (IBD). However, a proportion of patients does not respond to IFX or loses response over time. Population pharmacokinetic (PopPK) modelling is a promising approach for IFX dose optimization, but with the increasing number of PopPK models in literature, model evaluation is essential. The aims of this study are: (i) to validate the predictive performance of existing IFX PopPK models using a cohort of children with IBD; and (ii) to perform a Bayesian estimation of the most suitable model to predict the next IFX concentrations. Methods: PubMed was searched for IFX PopPK models in children. Selected models were rebuilt and analysed using R. Model performance was assessed through goodness‐of‐fit‐plots, residuals against time, prediction error and prediction‐corrected visual predictive checks. The validation cohort consisted of 73 children with IBD who were treated with IFX in our centre between 2017 and 2023 (340 IFX measurements). Results: We identified 9 PopPK models. Model bias for individual predicted values ranged from −9.29% to 8.01% compared to bias for population predicted values. The model by Vande Casteele et al. demonstrated superior performance (individual predicted bias 2.13, population predicted bias −6.11); upon Bayesian estimation, it predicted induction trough levels with median error of 12.95% but had a median error of −69% predicting maintenance concentrations. Conclusion: The model by Vande Casteele et al. displayed superior performance in initial evaluations but had a high error in estimating next IFX levels and can only be used in practice to predict induction levels. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease [IBD] is associated with various immune-mediated disorders including spondylarthritis, pyoderma gangrenosum, primary sclerosing cholangitis, and uveitis. Chronic kidney disease [CKD] is defined by a reduction in kidney function (estimated glomerular filtration rate [eGFR] less than 60 ml/min/1.73m2] and/or damage markers that are present for at least 3 months, regardless of the aetiology. Case reports and cohort studies suggest that IBD is associated with CKD. The extent and magnitude of a potential association is unknown. A comprehensive search was conducted in EMBASE, MEDLINE, Web of Science, the Cochrane database, and SCOPUS. Two separate reviewers were involved in the process of article selection and evaluation. Odds ratios were calculated in those papers with a comparison between an IBD population and a non-IBD control population, the Mantel Haenszel test was employed, using a random effect model. The systematic review was registered in PROSPERO [RD42023381927]. A total of 54 articles was included in the systematic review. Of these, eight articles included data on prevalence of CKD in IBD patients [ n  = 102 230] vs healthy populations [ n  = 762 430]. Of these, diagnosis of CKD was based on International Classification of Diseases [ICD] codes in five studies vs on eGFR in three studies. The overall odds ratio of developing CKD in the IBD population is 1.59, [95% CI 1.31-1.93], without any difference between studies using diagnostic coding (odds ratio [OR] 1.70, 95% CI 1.33-2.19] vs diagnosis based on eGFR [OR 1.36, 95% CI 1.33-1.64]. IBD is associated with a clinically meaningful increased CKD prevalence. We provide recommendations on diagnostic evaluation, as well as suggestions for future research. [ABSTRACT FROM AUTHOR]

The proper differentiation and reorganization of the intestinal epithelial cell population is critical to mucosal regeneration post injury. Label retaining cells (LRCs) expressing SRY-box transcription factor 9 (SOX9) promote epithelial repair by replenishing LGR5+ intestinal stem cells (ISCs). While, LRCs are also considered precursor cells for enteroendocrine cells (EECs) which exacerbate mucosal damage in inflammatory bowel disease (IBD). The factors that determine LRC-EEC differentiation and the effect of intervening in LRC-EEC differentiation on IBD remain unclear. In this study, we investigated the effects of a natural anthraquinone called aloe emodin (derived from the Chinese herb rhubarb) on mucosal healing in IBD models. Our findings demonstrated that aloe emodin effectively interfered with the differentiation to EECs and preserved a higher number of SOX9+ LRCs, thereby promoting mucosal healing. Furthermore, we discovered that aloe emodin acted as an antagonist of free fatty acid receptors (FFAR1), suppressing the FFAR1-mediated G βγ /serine/threonine-protein kinase (AKT) pathway and promoting the translocation of forkhead box protein O1 (FOXO1) into the nucleus, ultimately resulting in the intervention of differentiation fate. These findings reveal the effect of free fatty acid accessibility on EEC differentiation and introduce a strategy for promoting mucosal healing in IBD by regulating the FFAR1/AKT/FOXO1 signaling pathway. Aloe emodin acted as an antagonist of FFAR1, inhibiting the AKT-phosphorylated FOXO1 and promoting SOX9 expression, which eventually interrupted LRCs differentiation to EECs and promoted mucosal healing in colitis. [Display omitted] [ABSTRACT FROM AUTHOR]

Innate lymphoid cells (ILCs) are a group of lymphocytes that are devoid of antigen-specific receptors and are mainly found in tissues. The subtypes ILC1, 2, and 3 mirror T-cell functionality in terms of cytokine production and expression of key transcription factors. Although the majority of ILCs are found in tissue (tILCs), they have also been described within the circulation (cILCs). As a result of their better accessibility and putative prognostic value, human cILCs are getting more and more attention in clinical research. However, cILCs are in many aspects functionally distinct from their tILC counterparts. In fact, from the 3 ILC subsets found within the circulation, only for cILC2s could a clear functional correspondence to their tissue counterparts be established. Indeed, cILC2s are emerging as a major driver of allergic reactions with a particular role in asthma. In contrast, recent studies revealed that cILC1s and cILC3s are predominantly in an immature state and constitute progenitors for natural killer cells and ILCs, respectively. We provide an overview about the phenotype and function of the different cILC subtypes compared to tILCs in health and disease, including transcriptomic signatures, frequency dynamics, and potential clinical value. Furthermore, we will highlight the dynamics of the NKp44+ ILC3 subset, which emerges as prognostic marker in peripheral blood for inflammatory bowel disease and leukemia. [ABSTRACT FROM AUTHOR]

The enteric nervous system (ENS) interacts bidirectionally with the local immune system, responding to inflammation within the gastrointestinal (GI) tract. In a previous study using the same samples, several gene targets were identified as being differentially expressed in the inflamed colonic tissue of pigs challenged with dextran sodium sulphate (DSS). Additionally, animals in the basal DSS group, exhibited reduced growth and increased fecal and pathology scores, while the relative abundance of beneficial taxa was reduced and harmful bacteria increased. While changes in the innate immune response and barrier function are widely cited regarding inflammatory bowel disease (IBD), the effects of inflammation on the local structures of the enteric nervous system (ENS) are less well understood. Hence, the objectives of this study were to: (1) evaluate the expression of a range of functionally diverse neuroactive receptors, transporters and neurotrophic factors in RNA derived from the colonic tissue from the same pigs; (2) examine associations with these neuroactive components and inflammatory, barrier function and matrix remodeling targets. Mature pigs were split into two experimental groups: (1) basal diet (n = 10); (2) basal diet + DSS (n = 11). The pigs were orally challenged with DSS once daily for four days and sacrificed humanely. Colonic tissue was collected for gene expression analysis. Most of the targets evaluated in this study were present at low levels or in some cases were undetectable by QPCR, including the dopamine receptor DRD5 and the serotonin receptor HTR3A. The dopamine receptors (DRD1, DRD3, DRD4), serotonin receptor (HTR4), and other selected neuroactive receptors (GRM7, GABRA2) were down-regulated in the DSS-challenged animals relative to the basal group (p < 0.05). Most notably, DRD2, was up-regulated four-fold, suggesting an active process involving this receptor (p < 0.05). Relationships with (previously published) gene expression data from the same samples suggest that DRD1 and DRD2 are influenced by different pathways and may also be interlinked with matrix remodeling and, more specifically, genes relevant to the epithelial to mesenchymal transition (CDH1, CDH2, IL6, IL13, IL10, MMP1, MMP2) an important fibrotic process in the pathogenesis of IBD. [ABSTRACT FROM AUTHOR]

Alterations to intestinal microbiota are assumed to occur in the pathogenesis of inflammatory bowel disease (IBD). This study aims to analyze the association of fecal microbiota composition, body composition, and lipid characteristics in patients with Crohn's disease (CD). In our cross-sectional study, patients with CD were enrolled and blood and fecal samples were collected. Clinical and endoscopic disease activity and body composition were assessed and laboratory tests were made. Fecal bacterial composition was analyzed using the shotgun method. Microbiota alterations based on obesity, lipid parameters, and disease characteristics were analyzed. In this study, 27 patients with CD were analyzed, of which 37.0% were obese based on visceral fat area (VFA). Beta diversities were higher in non-obese patients (p < 0.001), but relative abundances did not differ. C. innocuum had a higher abundance at a high cholesterol level than Bacillota (p = 0.001, p = 0.0034). Adlercreutzia, B. longum, and Blautia alterations were correlated with triglyceride levels. Higher Clostridia (p = 0.009) and B. schinkii (p = 0.032) and lower Lactobacillus (p = 0.035) were connected to high VFA. Disease activity was coupled with dysbiotic elements. Microbiota alterations in obesity highlight the importance of gut microbiota in diseases with a similar inflammatory background and project therapeutic options. [ABSTRACT FROM AUTHOR]

A prevalent symptom among Inflammatory Bowel Disease (IBD) patients is fatigue, characterized by a persistent sense of energy depletion that affects all aspects of daily life. This review aims to evaluate nursing interventions reported in the literature to alleviate fatigue in IBD patients. A comprehensive search was conducted across four electronic databases—PubMed, CINAHL, Cochrane, and Scopus—and four scientific journals: "Gastroenterology", "Inflammatory Bowel Disease", "Journal of Crohn's and Colitis", and "United European Gastroenterology Journal". Inclusion criteria were clinical trials involving adult IBD patients in remission or mild disease activity. Out of 234 studies, 2 were selected for review. These studies assess the effectiveness of Solution-Focused Therapy (SFT) that emphasizes solving problems and developing strategies for improvement, and Problem-Solving Therapy (PST) that focuses on identifying problems and coping strategies. SFT showed a positive impact on fatigue with a significant improvement in the Checklist Individual Strength after three months: 45.5% in the control group, 85.7% in the SFT group, and 60% in the PST group, but its impact declined over time. Additionally, SFT demonstrated potential for reducing healthcare costs compared to standard of care and PST. Further research is needed to provide nurses interventions for managing fatigue in IBD patients. The review protocol has been registered at OSF.io. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease is a chronic inflammatory condition of the gut. It has two major subtypes Crohn's disease and ulcerative colitis. The follow-up consists of radiologic, molecular, endoscopic, and histological assessments. Intestinal ultrasound (IUS) is a noninvasive measure that provides future hope in guiding the management of IBD patients. This study is to assess the effectiveness of IUS in IBD patients' follow-up in our tertiary center during the pandemic. This is a prospective observational study during the COVID-19 pandemic. We used IUS to assess activity of IBD at baseline and at 6-month follow-up of patients on maintenance biological therapy using the following parameters: bowel haustrations, stratification, bowel wall thickness (BWT), Doppler sign (Limberg classification), presence of lymph nodes, or fibrofatty infiltration, echogenicity of the bowel, and presence of fistulae or abscesses. We compared the IUS with other radiologic parameters, histologic, and endoscopic scores at baseline before therapy, while we compared IUS with clinical scores and laboratory parameters before and after 24 weeks of biological treatment. Results: The cohort included 50 known IBD patients from June 2021 to January 2022. The laboratory studies showed a significant improvement in the hemoglobin indices, CRP, and fecal calprotectin from baseline and after 24 weeks. BWT, lumen diameter, lymph node presence, inflammatory signs, and Doppler activity signs were the most significant parameters in detecting improvement. However, there was no significant correlation between fecal calprotectin levels and ultrasound parameters. There was a positive correlation between MR and CT enterography, endoscopic parameters, and IUS parameters at baseline. Conclusions: IUS is an effective tool for follow-up of IBD patients especially during the pandemic periods. [ABSTRACT FROM AUTHOR]

Like TNFα, IL-6 is upregulated in Crohn's disease (CD) especially in patients associated with Mycobacterium avium paratuberculosis (MAP) infection, and both cytokines have been targeted as a therapeutic option for the treatment of the disease despite the accepted partial response in some patients. Limited response to anti-IL-6 receptor-neutralizing antibodies therapy may be related to the homeostatic dual role of IL-6. In this study, we investigated the effects and the signaling mechanism of IL-6 involved in intestinal epithelial integrity and function during MAP infection using an in vitro model that consists of THP-1, HT-29 and Caco-2 cell lines. Clinically, we determined that plasma samples from MAP-infected CD patients have higher IL-6 levels compared to controls (P-value < 0.001). In CD-like macrophages, MAP infection has significantly upregulated the secretion of IL-6 and the shedding of (IL-6R) from THP-1 macrophages, P-value < 0.05. Intestinal cell lines (Caco-2 and HT-29) were treated with the supernatant of MAP-infected THP-1 macrophages with or without a neutralizing anti-IL-6R antibody. Treating intestinal Caco-2 cells with supernatant of MAP-infected macrophages resulted in significant upregulation of intestinal damage markers including claudin-2 and SERPINE1/PAI-1. Interestingly, blocking IL-6 signaling exacerbated that damage and further increased the levels of the damage markers. In HT-29 cells, MAP infection upregulated MUC2 expression, a protective response that was reversed when IL-6R was neutralized. More importantly, blocking IL-6 signaling during MAP infection rescued damaged Caco-2 cells from MAP-induced apoptosis. The data clearly supports a protective role of IL-6 in intestinal epithelia integrity and function especially in CD patients associated with MAP infection. The findings may explain the ineffective response to anti-IL6 based therapy and strongly support a therapeutic option that restores the physiologic level of IL-6 in patient's plasma. A new treatment strategy based on attenuation of IL-6 expression and secretion in inflammatory diseases should be considered. [ABSTRACT FROM AUTHOR]

Chronic pain is a debilitating symptom with a significant negative impact on the quality of life and socioeconomic status, particularly among adults and the elderly. Major Depressive Disorder (MDD) stands out as one of the most important comorbid disorders accompanying chronic pain. The kynurenine pathway serves as the primary route for tryptophan degradation and holds critical significance in various biological processes, including the regulation of neurotransmitters, immune responses, cancer development, metabolism, and inflammation. This review encompasses key research studies related to the kynurenine pathway in the context of headache, neuropathic pain, gastrointestinal disorders, fibromyalgia, chronic fatigue syndrome, and MDD. Various metabolites produced in the kynurenine pathway, such as kynurenic acid and quinolinic acid, exhibit neuroprotective and neurotoxic effects, respectively. Recent studies have highlighted the significant involvement of kynurenine and its metabolites in the pathophysiology of pain. Moreover, pharmacological interventions targeting the regulation of the kynurenine pathway have shown therapeutic promise in pain management. Understanding the underlying mechanisms of this pathway presents an opportunity for developing personalized, innovative, and non-opioid approaches to pain treatment. Therefore, this narrative review explores the role of the kynurenine pathway in various chronic pain disorders and its association with depression and chronic pain. [ABSTRACT FROM AUTHOR]

Introduction: Ulcerative Colitis (UC) is an Inflammatory Bowel Disease (IBD). Surgery is required in cases of severe acute colitis, massive hemorrhage, toxic megacolon, and perforation; in such cases colectomy and JpouchIleoanal anastomosis (IPAA) are performed. The aim of this study was to evaluate functional outcome, and patient satisfaction and Quality of Life (QoL) after surgery. Material and methods: Questionnaires were administered to 24 patients with UC undergoing surgery from 2011 to 2022. Results: Mean age at IPAA was 10.8 years. Twenty patients underwent IPAA in 3 operations, 4 patients in 2. All patients underwent laparoscopic surgery. 6 months after surgery mean level of satisfaction was 8.7/10, perception of health status was 7.4. Twenty-three patients (95.8%) recommended IPAA. For 20 patients (83.3%) surgery did not cause delay in education, while 14 patients (58.3%) played sport. The lowest number of evacuations was 9.2 per day, the highest 13.3. Seventeen patients (70.8%) had no incontinence and 15 patients (62.5%) were not affected by pouchitis. After 12 months mean satisfaction level raised up to 9.2/10, perception of health status to 8.5. School absences decreased and no other patients showed any delay in education. Seventeen (70.8%) patients played sports. The number of evacuations decreased: the lowest number was 5.1 per day, the highest 7.5. Twenty patients (83.3%) were continent and 12 (50%) did not use antibiotics. Conclusion: Most patients show a good functional outcome in defecation frequency and continence, which has improved through time, number of pouchitis episodes has increased. Patients appear satisfied after surgery. [ABSTRACT FROM AUTHOR]

The mechanism underlying intestinal fibrosis, the main complication of inflammatory bowel disease (IBD), is not yet fully understood, and there is no therapy to prevent or reverse fibrosis. We evaluated, in in vitro cellular models, the ability of different classes of drugs currently used in IBD to counteract two pivotal processes of intestinal fibrosis, the differentiation of intestinal fibroblasts to activated myofibroblasts using CCD-18Co cells, and the epithelial-to-mesenchymal transition (EMT) of intestinal epithelial cells using Caco-2 cells (IEC), both being processes induced by transforming growth factor-β1 (TGF-β1). The drugs tested included mesalamine, azathioprine, methotrexate, prednisone, methylprednisolone, budesonide, infliximab, and adalimumab. The expression of fibrosis and EMT markers (collagen-I, α-SMA, pSmad2/3, occludin) was assessed by Western blot analysis and by immunofluorescence. Of the drugs used, only prednisone, methylprednisolone, budesonide, and adalimumab were able to antagonize the pro-fibrotic effects induced by TGF-β1 on CCD-18Co cells, reducing the fibrosis marker expression. Methylprednisolone, budesonide, and adalimumab were also able to significantly counteract the TGF-β1-induced EMT process on Caco-2 IEC by increasing occludin and decreasing α-SMA expression. This is the first study that evaluates, using in vitro cellular models, the direct antifibrotic effects of drugs currently used in IBD, highlighting which drugs have potential antifibrotic effects. [ABSTRACT FROM AUTHOR]

OCTN1 and OCTN2 are membrane transport proteins encoded by the SLC22A4 and SLC22A5 genes, respectively. Even though several transcripts have been predicted by bioinformatics for both genes, only one functional protein isoform has been described for each of them. Both proteins are ubiquitous, and depending on the physiopathological state of the cell, their expression is regulated by well-known transcription factors, although some aspects have been neglected. A plethora of missense variants with uncertain clinical significance are reported both in the dbSNP and the Catalogue of Somatic Mutations in Cancer (COSMIC) databases for both genes. Due to their involvement in human pathologies, such as inflammatory-based diseases (OCTN1/2), systemic primary carnitine deficiency (OCTN2), and drug disposition, it would be interesting to predict the impact of variants on human health from the perspective of precision medicine. Although the lack of a 3D structure for these two transport proteins hampers any speculation on the consequences of the polymorphisms, the already available 3D structures for other members of the SLC22 family may provide powerful tools to perform structure/function studies on WT and mutant proteins. [ABSTRACT FROM AUTHOR]

Background: Current therapy for patients suffering from inflammatory bowel diseases (IBD) is focused on inflammatory mechanisms exclusively and not the dysbiotic microbiota, despite growing evidence implicating a role for intestinal microbes in disease. Main body: Ongoing research into the intestinal microbiota of IBD patients, using new technologies and/or deeper application of existing ones, has identified a number of microorganisms whose properties and behaviors warrant consideration as causative factors in disease. Such studies have implicated both bacteria and fungi in the pathogenesis of disease. Some of these organisms manifest mechanisms that should be amenable to therapeutic intervention via either conventional or novel drug discovery platforms. Of particular note is a deeper characterization of microbial derived proteases and their destructive potential. Conclusion: Given the steady progress on the mechanistic role of the microbiota in inflammatory diseases, it is reasonable to anticipate a future in which therapeutics targeting microbial derived pathogenic factors play an important role in improving the lives of IBD patients. [ABSTRACT FROM AUTHOR]

The aim of the study was to determine long-term outcome in Crohn's disease patients hospitalised for acute abdominal pain. Retrospective chart review was made of consecutive Crohn's disease patients hospitalised for acute abdominal pain at the tertiary referral centre in Eastern Europe. Between 2015 and 2020, 65 patients with Crohn's disease were admitted at least once to the emergency room because of acute abdominal pain. Thirteen were admitted twice, eight — three times, three — four times, and three — five times. Most patients had ileal involvement. There were two intra-abdominal abscesses. Fifty-three of 65 underwent abdominal imaging. Forty-five were treated with antibiotics (65%), 17 with steroids (26%), eight received a nasogastric tube and three — parenteral nutrition. Six underwent an intestinal resection during the initial hospitalisation (9%). The hospitalisation length median was eight days and significantly longer in those who underwent surgery (28 vs. 9, p = 0.003). The median follow-up time was 42.8 months. During the follow-up period, 26 (40%) readmitted for abdominal emergencies, 14 underwent surgery — either at the initial or later hospitalisation (21%). Thirteen of 14 surgeries were emergencies, and three were concluded by ostomy formation (21%). One developed postoperative intra-abdominal complication, and two died postoperatively (14%). Complicated disease was associated with hospital readmission (HR, 5.8, 95% CI:1.4–23.3; p = 0.013) and enhanced probability to undergo intestinal surgery (HR, 10.3, 95% CI: 2.4–44.1; p = 0.002). An elevated CRP was associated with decreased risk of hospital readmission (HR, 0.08, 95% CI: 0.01–0.55; p = 0.010). Ileocolic disease was the main cause of hospitalisation for acute abdominal pain. Complicated (stricturing or penetrating) disease should be diagnosed early and surveilled closely. [ABSTRACT FROM AUTHOR]

Purpose: Paraprobiotics are a non-viable form of probiotics that are reported to provide significant health benefits. Nevertheless, little is known about the beneficial effects of paraprobiotics on inflammatory bowel disease. Although probiotics show potential as therapeutic agents for a range of diseases, including inflammatory bowel disease (IBD), there are certain risks associated with their use. These risks include toxin production, hemolytic potential, antibiotic resistance, and the need to analyze metabolic activities. Hence Using paraprobiotic with the lower aforementioned risk would therefore be the preferable option. Here, we conducted an in vivo study to evaluate the preventive effect of our native paraprobiotic cocktail against dextran sulfate sodium (DSS)-induced murine colitis by affecting the autophagy signaling pathway. Methods: Four-week-old male C57Bl/6 mice were randomly divided into three groups after a two-week acclimation period with normal standard laboratory food diet. Mice were administered PBS (PBS group as control), PBS along with DSS (DSS group, as a control), and a cocktail of paraprobiotics along with DSS (Para group). The severity of colitis, length and histopathology of the colon were evaluated. In addition, the expression of autophagy was assessed using real-time PCR. Results: The results showed that administration of the paraprobiotic cocktail to DSS-treated mice inhibited the severity of colitis symptoms, as evidenced by the inhibition of weight loss and DAI, as well as histopathological scores in the study colon, as well as shortening of colon length caused by DSS. In contrast to the DSS group, the cocktail was able to modulate inflammation through upregulation of autophagy-related genes (becline 1, atg5, atg7, atg12, and atg13). Conclusion: Although there are some limitations in our investigation, such as the dosage and duration of treatments, our native paraprobiotic blend effectively prevented the advancement of colitis. This suggests that it plays a vital role in regulating inflammation and preventing colitis by promoting the autophagy mechanism in cases where the consumption of probiotics may have negative consequences. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Inflammatory bowel diseases (IBD) are frequently diagnosed between the ages of 20 and 40, i.e. the most fertile period for women. The potential impact of IBD on pregnancy is therefore a frequent issue. Study objective: To determine the impact of disease activity during pregnancy on the obstetric prognosis of women with IBD. Methods: Gastroenterological and obstetric data were collected for patients for all consecutive patients with IBD and pregnancy followed up at Amiens University Hospital (Amiens, France) between 2007 and 2021. Obstetrics outcome of patients with and without active disease were compared. Results: One hundred patients were included (81 with Crohn's Disease for 198 pregnancies, 19 with Ulcerative Colitis for 37 pregnancies). Patients with active IBD (21 patients, 24 pregnancies) were more likely to be admitted to hospital during pregnancy (66.6, vs. 5.2% in the inactive IBD group; p < 0.001), to give birth prematurely (mean term: 36.77 weeks of amenorrhoea (WA) vs. 38.7 WA, respectively; p = 0.02) and to experience very premature delivery (before 32 WA: 12.5 vs. 1.4%, respectively; p = 0.02). Patients with active disease had a shorter term at birth (38.4 WA, vs. 39.8 WA in the inactive disease group; p < 0.0001), a lower birth weight (2707 g vs. 3129 g, respectively; p = 0.01) and higher caesarean section rate (54.2 vs. 16.9%, respectively; p = 0.03). Conclusion: Women with IBD patients are at risk of pregnancy related complications, especially when IBD is active. Controlling disease activity at conception and close monitoring of the pregnancy is essential to improve both gastroenterological and obstetric outcome. [ABSTRACT FROM AUTHOR]

Several studies have provided interesting evidence about the role of the bidirectional communication between the gut and brain in the onset and development of several pathologic conditions, including inflammatory bowel diseases (IBDs), neurodegenerative diseases, and related comorbidities. Indeed, patients with IBD can experience neurologic disorders, including depression and cognitive impairment, besides typical intestinal symptoms. In parallel, patients with neurodegenerative disease, such as Parkinson disease and Alzheimer disease, are often characterized by the occurrence of functional gastrointestinal disorders. In this context, enteric glial cells and brain astrocytes are emerging as pivotal players in the initiation/maintenance of neuroinflammatory responses, which appear to contribute to the alterations of intestinal and neurologic functions observed in patients with IBD and neurodegenerative disorders. The present review was conceived to provide a comprehensive and critical overview of the available knowledge on the morphologic, molecular, and functional changes occurring in the enteric glia and brain astroglia in IBDs and neurologic disorders. In addition, our intent is to identify whether such alterations could represent a common denominator involved in the onset of comorbidities associated with the aforementioned disorders. This might help to identify putative targets useful to develop novel pharmacologic approaches for the therapeutic management of such disturbances. [ABSTRACT FROM AUTHOR]

Peach (Prunus persica), a significant economic fruit tree in the Rosaceae family, is extensively cultivated in temperate and subtropical regions due to its abundant genetic diversity, robust adaptability, and high nutritional value. Originating from China over 4000 years ago, peaches were introduced to Persia through the Silk Road during the Han Dynasty and gradually spread to India, Greece, Rome, Egypt, Europe, and America. Currently grown in more than 80 countries worldwide, the expansion of peach cultivation in Egypt is mainly due to the development and utilization of peach varieties with low chilling requirements. These varieties exhibit unique phenotypic characteristics such as early maturity, reduced need for winter cold temperatures, low water requirements, and high economic value. In this study, a systematic analysis was conducted on the genetic characteristics and kinship relationships of peaches with low chilling requirements in Egypt. We conducted a comprehensive evolutionary and Identity-by-Descent (IBD) analysis on over 300 peach core germplasm resources, including Egyptian cultivars with low chilling requirements, to investigate their origin and genetic characteristics. The evolutionary analysis revealed that 'Bitter almond' is closely related to China's wild relative species Prunus tangutica Batal, while 'Early grand' shares one branch with Chinese ornamental peach cultivars, and 'Nemaguard' clusters with some ancient local varieties from China. The IBD analysis also indicated similar genetic backgrounds, suggesting a plausible origin from China. Similarly, the analysis suggested that 'Swelling' may have originated from the Czech Republic while 'Met ghamr' has connections to South Africa. 'Desert red', 'Early swelling', and 'Florida prince' are likely derived from Brazil. These findings provide valuable insights into the genetic characteristics of Egyptian peach cultivars. They offer a significant foundation for investigating the origin and spread of cultivated peaches worldwide and serve as a valuable genetic resource for breeding low chilling requirement cultivars, which is of considerable significance for the advancement of peach cultivation in Egypt. [ABSTRACT FROM AUTHOR]

Cyclic nucleotide phosphodiesterases (PDEs) consist of a family of enzymes expressed in several types of cells, including inflammatory cells, that play a pivotal role in inflammation. Several studies have demonstrated that the inhibition of PDE4 results in a reduced inflammatory response via PKA and CREB signaling. Hence, PDE4 suppression improves the inflammatory feedback typical of several diseases, such as inflammatory bowel disease (IBD). In our previous studies, we have demonstrated that miR-369-3p regulates inflammatory responses, modulating different aspects of the inflammatory process. The aim of this study was to demonstrate an additional anti-inflammatory effect of miR-369-3p targeting PDE4B, one of the widely expressed isoforms in immune cells. We found that miR-369-3p was able to reduce the expression of PDE4B, elevating the intracellular levels of cAMP. This accumulation increased the expression of PKA and pCREB, mitigating the release of pro-inflammatory cytokines and promoting the release of anti-inflammatory cytokines. To prove that PDE4B is a good therapeutic target in IBD, we also demonstrate that the expression of PDE4B was increased in UC patients compared to healthy controls, affecting the immune infiltrate. PDE4B is considered an important player in inflammatory progression; hence, our results show the ability of miR-369-3p to ameliorate inflammation by targeting PDE4B, supporting its future application as a new therapeutic approach in IBD. [ABSTRACT FROM AUTHOR]

Background: This study sought to explore the effect of electroacupuncture (EA) intervention at Zusanli (ST36) acupoint on modulating the NLRP3 inflammasome pathway for treating inflammatory bowel disease (IBD). Methods: C57BL/6 mice were administrated with 3% dextran sulfate sodium (DSS) to construct the IBD model. DSS mice were then administrated with EA (10 Hz, 1.5 mA) at ST36 for 7 days or intragastric administration of sulfasalazine (SASP) each day during the entire course. The control group animals were administered with distilled water. Then, partial least squares discriminant analysis revealed differences in the relative content of metabolites. The pathological changes of colon and spleen tissues were observed by H&E and immunohistochemistry (IHC) staining. qPCR determined the mRNA expression levels, while ELISA and western blot analysis determined the protein expression. Results: Compared with the control groups, DSS‐induced decreases of body weight were reversed after EA stimulation at ST36 or SASP treatment. The DAI of DSS mice was significantly higher relative to the control groups, whereas the DAI of DSS mice were decreased after EA stimulation at ST36 or SASP treatment. The intestinal weight/length ratio increased significantly in DSS groups; however, EA at ST36 significantly improved the macroscopic/microscopic characteristics and the weight and length of the colon. EA reversed inflammation and leukocyte infiltration and normalized the elevated levels of IL‐1β, IL‐18, and NLRP3. Furthermore, EA improved the expression levels of ZO‐1, occludin, and claudin 1, exhibiting normalization of the colon's tight junctions. Conclusions: EA at Zusanli acupoint of colon tissue significantly improved the pathological phenotype, showing a therapeutic effect on IBD. [ABSTRACT FROM AUTHOR]

Inflammation is an important pathophysiological process in many diseases; it has beneficial and harmful effects. When exposed to various stimuli, the body triggers an inflammatory response to eliminate invaded pathogens and damaged tissues to maintain homeostasis. However, uncontrollable persistent or excessive inflammatory responses may damage tissues and induce various diseases, such as metabolic diseases (e.g. diabetes), autoimmune diseases, nervous system‐related diseases, digestive system‐related diseases, and even tumours. Aldo‐keto reductase 1B10 (AKR1B10) is an important player in the development and progression of multiple diseases, such as tumours and inflammatory diseases. AKR1B10 is upregulated in solid tumours, such as hepatocellular carcinoma (HCC), non‐small cell lung carcinoma, and breast cancer, and is a reliable serum marker. However, information on the role of AKR1B10 in inflammation is limited. In this study, we summarized the role of AKR1B10 in inflammatory diseases, including its expression, functional contribution to inflammatory responses, and regulation of signalling pathways related to inflammation. We also discussed the role of AKR1B10 in glucose and lipid metabolism and oxidative stress. This study provides novel information and increases the understanding of clinical inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background and Aims Anti-tumour necrosis factor [TNF] treatment failure in patients with inflammatory bowel disease [IBD] is common and frequently related to low drug concentrations. In order to identify patients who may benefit from dose optimisation at the outset of anti-TNF therapy, we sought to define epigenetic biomarkers in whole blood at baseline associated with anti-TNF drug concentrations at week 14. Methods DNA methylation from 1104 whole blood samples from 385 patients in the Personalised Anti-TNF Therapy in Crohn's disease [PANTS] study were assessed using the Illumina EPIC Beadchip [v1.0] at baseline and weeks 14, 30, and 54. We compared DNA methylation profiles in anti-TNF-treated patients who experienced primary non-response at week 14 if they were assessed at subsequent time points and were not in remission at week 30 or 54 [infliximab n = 99, adalimumab n = 94], with patients who responded at week 14 and when assessed at subsequent time points were in remission at week 30 or 54 [infliximab n = 99, adalimumab n = 93]. Results Overall, between baseline and week 14, we observed 4999 differentially methylated positions [DMPs] annotated to 2376 genes following anti-TNF treatment. Pathway analysis identified 108 significant gene ontology terms enriched in biological processes related to immune system processes and responses. Epigenome-wide association [EWAS] analysis identified 323 DMPs annotated to 210 genes at baseline associated with higher anti-TNF drug concentrations at Week 14. Of these, 125 DMPs demonstrated shared associations with other common traits [proportion of shared CpGs compared with DMPs] including body mass index [23.2%], followed by C-reactive protein [CRP] [11.5%], smoking [7.4%], alcohol consumption per day [7.1%], and IBD type [6.8%]. EWAS of primary non-response to anti-TNF identified 20 DMPs that were associated with both anti-TNF drug concentration and primary non-response to anti-TNF with a strong correlation of the coefficients [Spearman's rho = -0.94, p <0.001]. Conclusion Baseline DNA methylation profiles may be used as a predictor for anti-TNF drug concentration at week 14 to identify patients who may benefit from dose optimisation at the outset of anti-TNF therapy. [ABSTRACT FROM AUTHOR]

Background We aimed to explore the epidemiology of inflammatory bowel diseases [IBD] in association with the COVID-19 pandemic in two countries with different lockdown policies. Methods We utilized nationwide IBD cohorts in Israel and Sweden to explore the incidence of IBD during the pandemic compared to 3 years prior [2017–2019]. We examined temporal trends through the presence of inflection points by Joinpoint regression analysis and reported average monthly percentage changes [AMPC]. Results A total of 155 837 patients with IBD were included [Israel, 58 640; Sweden, 97 197]. The annual incidence of IBD was stable until 2019 in both countries but then decreased in Israel (AAPC −16.6% [95% confidence interval, CI, −19.9% to −10.0%]) and remained stable in Sweden (AAPC −3.5% [95% CI −11.6% to 3.7%]). When exploring the monthly incidence during the pandemic, in Israel the rate remained stable until November 2020 (AMPC 2.3% [95% CI −13.4% to 29.9%]) and then decreased sharply (AMPC –6.4% [95% CI –20.8% to 17.0%] until February 2021 and to −20.1% [95% CI –38.9% to –4.7%] from February 2021), while in Sweden, which had a less stringent lockdown policy, it decreased slightly until July 2020 (AMPC −3.3% [95% CI −21.6% to 20.3%]), but increased thereafter (AMPC 13.6% [95% CI –12.6% to 27.0%]). The change of incidence rate in Sweden occurred mainly in elderly-onset patients, the only population with significant restrictions during the pandemic. Conclusion The incidence of IBD decreased during the pandemic in association with lockdowns, more so in Israel, which had more stringent policies. Future studies are needed to determine the long-term effect of the pandemic on IBD. [ABSTRACT FROM AUTHOR]

Most animals have large amounts of the special substance melatonin, which is controlled by the light/dark cycle in the suprachiasmatic nucleus. According to what is now understood, the gastrointestinal tract (GIT) and other areas of the body are sites of melatonin production. According to recent studies, the GIT and adjacent organs depend critically on a massive amount of melatonin. Not unexpectedly, melatonin's many biological properties, such as its antioxidant, anti-inflammatory, pro-apoptotic, anti-proliferative, anti-metastasis, and antiangiogenic properties, have drawn the attention of researchers more and more. Because melatonin is an antioxidant, it produces a lot of secretions in the GIT's mucus and saliva, which shields cells from damage and promotes the development of certain GIT-related disorders. Melatonin's ability to alter cellular behavior in the GIT and other associated organs, such as the liver and pancreas, is another way that it functions. This behavior alters the secretory and metabolic activities of these cells. In this review, we attempted to shed fresh light on the many roles that melatonin plays in the various regions of the gastrointestinal tract by focusing on its activities for the first time. [ABSTRACT FROM AUTHOR]

Nutritional epidemiological studies have evolved from a focus of single nutrients to diet patterns to capture the protective role of healthy diets on chronic disease development. Similarly, in inflammatory bowel disease (IBD), a healthy diet may be protective against its development in individuals with genetic susceptibility, but the definitions of the optimal diet pattern deserve further exploration. Hence, this review article presents evidence, mainly from prospective cohort studies, for the role of diet quality based on adherence to dietary guidelines, traditional and modern diet patterns in the prevention of IBD. Findings from a limited number of studies on diet quality suggest that high diet quality scores are associated with lower risk of developing Crohn's disease, but the data are inconsistent for ulcerative colitis (UC). There are signals that a Mediterranean diet pattern reduces the risk of Crohn's disease but, again, the data are inconsistent and further studies are much needed. Finally, the evidence is conflicting regarding the role of food additives, with difficulties in the assessment of their intake, namely non‐nutritive sweeteners and emulsifiers, precluding accurate assessment of a relationship with IBD risk. In contrast, emerging evidence for a role of ultra‐processed food in the development of Crohn's disease but not UC is identified. Given the potential influence of diet quality, a Mediterranean diet and ultra‐processed food intake on the risk of Crohn's disease, assessment and implementation of dietary advice for these patients need to be tailored. The search for an optimal diet for UC remains elusive and further research for increasing the evidence in the area is greatly needed. [ABSTRACT FROM AUTHOR]

Background: Keratoconus is a diseased corneal dilation of unknown etiology. Studies have shown that inflammation may play a role in keratoconus. Inflammatory enteritis (IBD), including ulcerative colitis (UC), is a chronic, systemic inflammatory disease. We used Mendelian randomization to assess the causal relationship among IBD, UC and keratoconus. Methods: The instrumental variable of IBD and UC was selected, the information of the instrumental variable in keratoconus outcome was extracted, and the causal relationship was assessed by the inverse variance weighted method by primary analysis, and its relevant sensitivity analysis. Results: A causal relationship between IBD and keratoconus was observed significantly (P = 0.017, OR = 1.21, 95% CI = 1.03-1.41), and same as to UC and keratoconus (P = 0.038, OR = 1.25, 95% CI = 1.01-1.54). Conclusion: IBD may play a causal role in the development of keratoconus, but the mechanism needs to be further elucidated. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chronic granulomatous disease (CGD) is caused by defects in any 1 of the 6 subunits forming the nicotinamide adenine dinucleotide phosphate oxidase complex 2 (NOX2), leading to severely reduced or absent phagocyte-derived reactive oxygen species production. Almost 50% of patients with CGD have inflammatory bowel disease (CGD-IBD). While conventional IBD therapies can treat CGD-IBD, their benefits must be weighed against the risk of infection. Understanding the impact of NOX2 defects on the intestinal microbiota may lead to the identification of novel CGD-IBD treatments. OBJECTIVE: We sought to identify microbiome and metabolome signatures that can distinguish individuals with CGD and CGD-IBD. METHODS: We conducted a cross-sectional observational study of 79 patients with CGD, 8 pathogenic variant carriers, and 19 healthy controls followed at the National Institutes of Health Clinical Center. We profiled the intestinal microbiome (amplicon sequencing) and stool metabolome, and validated our findings in a second cohort of 36 patients with CGD recruited through the Primary Immune Deficiency Treatment Consortium. RESULTS: We identified distinct intestinal microbiome and metabolome profiles in patients with CGD compared to healthy individuals. We observed enrichment for Erysipelatoclostridium spp, Sellimonas spp, and Lachnoclostridium spp in CGD stool samples. Despite differences in bacterial alpha and beta diversity between the 2 cohorts, several taxa correlated significantly between both cohorts. We further demonstrated that patients with CGD-IBD have a distinct microbiome and metabolome profile compared to patients without CGD-IBD. CONCLUSION: Intestinal microbiome and metabolome signatures distinguished patients with CGD and CGD-IBD, and identified potential biomarkers and therapeutic targets.

Abstract Background Our previous study has demonstrated a decreased colonic CD8+CD39+ T cells, enrichment of granzyme A (GZMA), was found in pediatric-onset colitis and inflammatory bowel disease (IBD) characterized by impaired intestinal barrier function. However, the influence of GZMA on intestinal barrier function remains unknown. Methods Western blotting(WB), real-time PCR (qPCR), immunofluorescence (IF) and in vitro permeability assay combined with intestinal organoid culture were used to detect the effect of GZMA on intestinal epithelial barrier function in vivo and in vitro. Luciferase, immunoprecipitation (IP) and subcellular fractionation isolation were performed to identify the mechanism through which GZMA modulated intestinal epithelial barrier function. Results Herein, we, for the first time, demonstrated that CD8+CD39+ T cells promoted intestinal epithelial barrier function through GZMA, leading to induce Occludin(OCLN) and Zonula Occludens-1(ZO-1) expression, which was attributed to enhanced CDX2-mediated cell differentiation caused by increased glutathione peroxidase 4(GPX4)-induced ferroptosis inhibition in vivo and in vitro. Mechanically, GZMA inhibited intestinal epithelial cellular PDE4B activation to trigger cAMP/PKA/CREB cascade signaling to increase CREB nuclear translocation, initiating GPX4 transactivity. In addition, endogenous PKA interacted with CREB, and this interaction was enhanced in response to GZMA. Most importantly, administration of GZMA could alleviate DSS-induced colitis in vivo. Conclusion These findings extended the novel insight of GZMA contributed to intestinal epithelial cell differentiation to improve barrier function, and enhacement of GZMA could be a promising strategy to patients with IBD.

Purpose: to characterize changes in the colon crypts in colitis and to assess their significance in the morphological diagnosis of inflammatory bowel diseases (IBD). Materials and methods: colon biopsies were retrospectively reviewed in patients with IBD (30 patients with ulcerative colitis (UC) and 30 patients with Crohn's disease (CD)) and in 30 patients where the diagnosis of IBD was not confirmed (self-limiting colitis not related to IBD (non-IBD)). The age of the patients ranged from 19 to 53 years. In all cases, the diagnosis was established based on a combination of clinical, laboratory, and instrumental diagnostic methods. Multiple biopsies were obtained from all patients during colonoscopy. The processing of the material was carried out according to generally accepted methodology. All cases were scanned using the Aperio TC histological preparation scanner (Leica, Germany) and re-examined with an emphasis on crypt changes. Results: the crypt characteristics found during the study were divided into the following groups. The most frequently detected changes included inflammatory and destructive changes (98% of cases of IBD and 80% of cases of non-IBD). Atrophic changes in crypts were more often found in patients with non-IBD colitis compared with cases of IBD (30% in IBD and 53.3% in non-IBD; p=0.03). Significant differences in frequency were observed when dysregenerative changes in crypts were detected (76.7% of cases of colitis in IBD and 13.3% of cases in non-IBD; p

Purpose: To provide a morphological characterization of dysplasia occurring against the background of inflammatory bowel disease (IBD), considering the new classification of dysplasia. Materials and methods. A retrospective analysis was conducted, and biopsies were reviewed from 257 patients with IBD treated at Sechenov University clinics from 2018 to 2023. Patients' ages ranged from 19 to 63 years. Diagnosis was based on a combination of clinical, laboratory, and instrumental methods. Multiple biopsies were taken during colonoscopy, processed using standard metods. Results. Non-traditional dysplasia was diagnosed in 5 patients, accounting for 1.95% of cases over a 6-year period. Two cases involved hypermucinous dysplasia in patients aged 35 and 43 with ulcerative colitis, with disease durations of 12 and 9 years, respectively. crypt cell atypia/dysplasia was diagnosed in two patients aged 40 and 30, with ulcerative colitis durations of 5 and 10 years, respectively. In a 51- year-old patient with Crohn's disease for over 15 years, dysplasia resembling a dentate lesion was found in the ascending intestine. Dysplasia diagnosis was confirmed using immunohistochemical (IHC) staining with TP53 antibodies (clone DO-7 Leica RTU, Germany), showing positive staining of tumor cell nuclei, indicating TP53 gene mutation. Two out of five cases exhibited total colon involvement in inflammatory process, and one ulcerative colitis case was combined with primary sclerosing cholangitis. Conclusion. Before the appearance of the latest classifications of dysplasia in IBD, we rarely diagnosed dysplasia in biopsies from IBD patients. We now understand that the spectrum of potential neoplastic precursor lesions of colorectal cancer in IBD patients is much wider and this understanding can ensure that clinically important but rare lesions will not be undiagnosed. Future studies of their natural course may eventually determine that some lesions are more clinically important than others.