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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]

Herbal medicines are used by patients with IBD despite limited evidence. We present a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating treatment with herbal medicines in active ulcerative colitis (UC). A search query designed by a library informationist was used to identify potential articles for inclusion. Articles were screened and data were extracted by at least two investigators. Outcomes of interest included clinical response, clinical remission, endoscopic response, endoscopic remission, and safety. We identified 28 RCTs for 18 herbs. In pooled analyses, when compared with placebo, clinical response rates were significantly higher for Indigo naturalis (IN) (RR 3.70, 95% CI 1.97-6.95), but not for Curcuma longa (CL) (RR 1.60, 95% CI 0.99-2.58) or Andrographis paniculata (AP) (RR 0.95, 95% CI 0.71-1.26). There was a significantly higher rate of clinical remission for CL (RR 2.58, 95% CI 1.18-5.63), but not for AP (RR 1.31, 95% CI 0.86-2.01). Higher rates of endoscopic response (RR 1.56, 95% CI 1.08-2.26) and remission (RR 19.37, 95% CI 2.71-138.42) were significant for CL. CL has evidence supporting its use as an adjuvant therapy in active UC. Research with larger scale and well-designed RCTs, manufacturing regulations, and education are needed.

Background: Children with inflammatory bowel disease (IBD) experience extraintestinal side effects including altered body composition, impaired muscle strength, and aerobic capacity. Exercise training may remedy these issues. Purpose: To assess the feasibility, safety, participant satisfaction, and efficacy of a training program for youth with IBD. Methods: Children with IBD completed 16 weeks of training (2 supervised + 1 home sessions per week). Feasibility was assessed by tracking recruitment, adherence, and compliance rates. Safety was assessed by tracking symptoms and adverse events. Posttraining interviews gauged satisfaction. Circulating inflammatory markers, body composition, muscle strength, aerobic fitness, and habitual physical activity were measured at baseline, midtraining (8 wk), and posttraining. Results: Eleven youth were recruited and 10 completed the study. Participants adhered to 28 (1) of 32 prescribed supervised sessions and 8 (4) of 16 prescribed home sessions. There were no adverse events, and overall feedback on training was positive. Posttraining, we observed an increase in lean mass (+2.4 [1.1] kg), bone density (+0.0124 [0.015] g·cm−2), aerobic fitness (+2.8 [5.7] mL·kg LM−1· min−1), and vigorous physical activity levels (+13.09 [8.95] min·h−1) but no change in inflammation or muscle strength. Conclusion: Supervised exercise training is feasible, safe, and effective for youth with IBD and should be encouraged. [ABSTRACT FROM AUTHOR]

A plant-based diet has a wealth of pro-health properties. These have been typically attributed to the beneficial effects associated with fruits, vegetables, juices and spices and the various properties of their phytochemical constituents, such as polyphenols. Inflammatory bowel diseases (IBD) are chronic disorders with an unknown etiology; however, an important component of IBD is colon damage, known to be caused by the inflammatory response, oxidative stress or disturbances of the gut microbiota. This review summarizes the current state of knowledge concerning the effects of polyphenol-rich extracts on IBD and assesses their utility. Most of the presented evidence suggests that polyphenol-rich extracts have various beneficial anti-inflammatory and anti-oxidative effects, enhancing the epithelial barrier and restoring disturbances in the gut microbiota. These effects may result from the modulation of multiple cellular signalling pathways. Based on these findings, new dietary strategies supporting the treatment of IBD may be created. [ABSTRACT FROM AUTHOR]

Background: Histology has prognostic value in ulcerative colitis (UC). However, direct comparisons of histological endpoints are lacking. Aim: To perform a network meta‐analysis (NMA) to compare histological endpoints with biologics and small molecules. Methods: We searched four databases up until July 2024 for randomised controlled trials (RCTs) on advanced therapies for moderate‐to‐severe UC reporting histological endpoints. Outcomes included histological improvement or remission, and histo‐endoscopic improvement after induction or during maintenance. We used a random‐effects frequentist model and have reported outcomes as relative risk and 95% confidence interval. We estimated relative drug efficacy with the P‐score. We conducted subgroup analysis by trial phase and evaluated risk of bias and evidence certainty. Results: We included 24 RCTs (15 therapies, 8874 patients). Nineteen provided data on induction and 10 on maintenance; outcome definitions were similar. Etrasimod 2 mg/day ranked highest in achieving histologic improvement (P‐score 0.98) and remission (P‐score 0.90) following induction. Globally, guselkumab 200–400 mg ranked first for histo‐endoscopic improvement, while etrasimod 2 mg/day and upadacitinib 45 mg/day were superior in the subgroup analysis. During maintenance, upadacitinib 30 mg/day was superior in achieving histologic improvement and remission (P‐score 0.88 for both) and histo‐endoscopic improvement (P‐score 0.94). Etrasimod 2 mg/day ranked second for histologic remission (P‐score 0.70) and histo‐endoscopic improvement (P‐score 0.73), while mirikizumab 200 mg/month ranked second for histologic improvement. Conclusion: These results support the ability of small molecules to achieve stringent endpoints in moderate‐to‐severe UC. Histological outcome data for biologics was sparser, particularly during maintenance. Head‐to‐head RCTs are imperative to better inform clinical practice. [ABSTRACT FROM AUTHOR]

Summary: Background: There are inconsistencies in the results of the studies investigating the association between inflammatory bowel disease (IBD) and lymphoma. Aims: The aim of this study is to systematically appraise the risk of lymphoma development in patients with IBD. Methods: We searched Embase, PubMed and Scopus from inception to 30 April 2024 to identify population‐based cohort studies that evaluated the risk of lymphoma in patients with IBD in comparison with those without IBD. We carried out random‐effects meta‐analyses and estimated pooled relative risks (RRs) with 95% confidence intervals (CIs). Results: We identified 23 eligible studies reporting 2078 lymphoma events in 656,731 patients with IBD. Patients with IBD had 30% higher odds of lymphoma (RR = 1.30 [95% CI: 1.21–1.40]). The risk of developing both Hodgkin's lymphoma (nine studies, RR = 1.29 [95% CI: 1.06–1.53]) and non‐Hodgkin's lymphoma (16 studies, RR = 1.31 [95% CI: 1.20–1.42]) was increased in patients with IBD (p for interaction = 0.881). The increased risk of lymphoma was observed in both Crohn's disease (17 studies, RR = 1.54 [95% CI: 1.27–1.80]) and ulcerative colitis (20 studies, RR = 1.22 [95% CI: 1.09–1.35]) (p for interaction = 0.026). Meta‐regression demonstrated that mean age of patients, study year, mean study follow‐up duration, and percentages of immunomodulators and biologics use did not influence study outcome. Conclusions: The risk of lymphoma is only modestly increased in patients with IBD, with Crohn's disease having a slightly higher risk than ulcerative colitis. In IBD, there appears to be no difference between the risks of Hodgkin's and non‐Hodgkin's lymphoma. [ABSTRACT FROM AUTHOR]

Summary: Background: Previous studies highlighted a more extensive phenotype for paediatric‐onset than adult‐onset inflammatory bowel disease (IBD). However, most lacked long‐term follow‐up, and some were conducted before the era of biologics. Aims: The aim of this study is to compare disease characteristics and treatment exposures between paediatric‐onset and adult‐onset IBD. Methods: From a registry that periodically and uniformly retrieves demographics, disease characteristics/phenotype, and treatments, we compared the characteristics of paediatric‐onset (diagnosed at ≥6 and <18 years) and adult‐onset IBD, diagnosed during 2000–2022 and with ≥12 months follow‐up. Results: Of the 2837 patients with Crohn's disease and 1332 with ulcerative colitis, 3316 had adult‐onset and 853 paediatric‐onset IBD. The median follow‐up was 6 years. Patients with paediatric‐onset presented with more extensive disease and received more intensified therapies, including biologics and JAK inhibitors than those with adult‐onset IBD. Paediatric‐onset ulcerative colitis showed a higher prevalence of E3 extensive colitis including pancolitis and a greater requirement for systemic steroids, immunomodulators, and biologics than adult‐onset ulcerative colitis. Paediatric‐onset versus adult‐onset Crohn's disease exhibited greater L3 ileocolonic involvement and perianal disease phenotype, and higher exposure to immunomodulators and biologics. Kaplan–Meier curve and Cox proportional hazards analyses showed significantly lower 15‐year biologic‐free survival from diagnosis among those with paediatric‐onset IBD than with adult‐onset IBD (p = <0.001), indicating greater and earlier use of biologics in the former. Conclusions: Paediatric‐onset presents with more extensive disease with higher exposures to immunomodulators and biologic therapies than adult‐onset IBD. [ABSTRACT FROM AUTHOR]

Summary: Background: To prevent complications of paediatric ulcerative colitis (UC), it is critical to understand their predictors. The Paediatric Inflammatory Bowel Disease Ahead (PIBD Ahead) program identified the relevant outcomes and their potential predictors. However, external validation of these results in larger cohorts is required. Aims: The aim of this study is to investigate these outcomes and their predictors. Methods: We included 743 patients aged under 18 years with UC from the multicentre German‐Austrian CEDATA‐GPGE registry. We performed Cox regressions, Kaplan–Meier estimator, and receiver operating characteristics curve analyses to analyse predictors of poor outcomes. Results: Older age at diagnosis was associated with relapse, hospitalisation, the use of immunomodulators, use of biologics, and therapy escalation. Higher disease activity, as in acute severe colitis in the first 3 months, was significantly associated with further acute severe colitis and the need for biologics. Upper gastrointestinal tract involvement was a risk factor for the need of intravenous corticosteroids and biologics. A faecal calprotectin of >685 μg/g was associated with a higher risk of subsequent acute severe colitis with a sensitivity of 79.0% and a specificity of 59.1%. A lower haematocrit at diagnosis was predictive of the use of biologics. Colectomy was rare. Conclusions: This study validates predictors of poor outcomes in paediatric patients with UC. Our results might help physicians to anticipate poor outcomes and initiate appropriate treatment strategies at an early stage. [ABSTRACT FROM AUTHOR]

Summary: Background: Ustekinumab is approved for ulcerative colitis (UC). Aims: To assess the durability of ustekinumab in patients with UC and its short‐term effectiveness, durability and tolerability in clinical practice. Methods: Retrospective, multicentre study of patients who had received their first ustekinumab dose at least 16 weeks before inclusion. Patients were followed until treatment discontinuation or last visit. Only patients with active disease at the start of ustekinumab treatment were considered in the effectiveness analysis. Patients who stopped ustekinumab before their last visit were considered not to be in subsequent remission. Results: We included 620 patients; 155 (25%) discontinued ustekinumab during follow‐up (median 12 months). Rate of discontinuation was 20% per patient‐year of follow‐up. Anaemia at baseline (hazard ratio, HR 1.5; 95% confidence interval [CI] 1.1–2.1), steroids at baseline (HR 1.5; 95% CI 1.06–2.08) and more severe clinical activity at baseline (HR 1.5; 95% CI 1.09–2.06) were associated with higher risk of discontinuation. At the end of induction, 226 (40%) patients were in steroid‐free clinical remission. Moderate–severe vs mild disease activity at baseline (odds ratio [OR] 0.3; 95% CI 0.2–0.5), male sex (OR 0.5; 95% CI 0.4–0.8), and increased number of previous biologics (OR 0.6; 95% CI 0.6–0.8) were associated with lower likelihood of steroid‐free clinical remission at week 16. One hundred and seventy‐six patients (28%) had at least one adverse event. We observed no negative impact of ustekinumab on extraintestinal manifestations and/or immune‐mediated diseases. Conclusions: Ustekinumab durability in UC was relatively high, and treatment was effective in highly refractory patients. The safety profile was consistent with previous studies. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is associated with the shedding of the gut mucus. Decellularized porcine small intestinal submucosa (SIS‐ECM) contains numerous active forms of extracellular matrix as well as growth factors. Herein, a mucus‐mimetic hydrogel (MAG) is designed as a barrier therapy by integrating SIS‐ECM with hyaluronic acid and epigallocatechin‐3‐gallate. MAG not only presented the viscoelastic behaviors with G' of 4000 Pa but also good thixotropy. Moreover, MAG as a physical shielding is effective to hinder E. coli invasion. Besides, the good repairing effect on the injured Caco‐2 cells is presented by MAG. When MAG as a biomimetic mucus is rectally administrated to colitis mouse, it alleviated effectively the colitis symptoms and improved the colonic shorting. Moreover, expression of IL‐1β, IL‐6, and TNF‐α at the laminae propria is substantially inhibited by MAG. Besides, the colonic epitheliums are well rearranged, and the tight junction proteins (ZO‐1, Occludin‐1, Claudin‐5) between them are greatly upregulated after MAG treatment. Meanwhile, the mucus secretion of goblets cells is effectively repaired by MAG treatment. The repairing mechanism of intestinal mucosa barriers is associated with promoting the proliferation and differentiation of intestinal stem cells. Collectively, MAG might be a promising strategy of barrier therapy for UC. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor alpha inhibitors (TNFi) are biological drugs used worldwide to treat various autoimmune disorders. Paradoxically, TNF‐α antagonists can also induce autoimmune diseases being systemic vasculitis, systemic lupus erythematosus, and psoriasis, the most common. We present a 22‐year‐old woman with ulcerative colitis (UC) who was started on adalimumab 40 mg subcutaneously every 2 weeks. After two doses of adalimumab, she developed gangrene of all toes and acute kidney injury requiring hemodialysis. Skin biopsy showed thrombi in the small vessels of the dermis. Renal biopsy disclosed diffuse proliferative glomerulonephritis (GN) and acute tubulointerstitial nephritis. Serologic work‐up showed positive IgG anticardiolipin (ACL) antibodies and low C3 levels. Antinuclear, anti‐dsDNA, anti‐Smith, anti‐SSA, anti‐SSB, anti‐RNP, antineutrophil cytoplasmic antibodies, ACL (IgA and IgM), and anti‐β2‐glycoprotein I (IgG, IgM, and IgA) antibodies were not elevated. Lupus anticoagulant test and cryoglobulins were negative. Adalimumab was discontinued, and she was treated with enoxaparin, intravenous (IV) methylprednisolone pulse, IV cyclophosphamide, and plasmapheresis followed by maintenance therapy with warfarin, prednisone, azathioprine, and hydroxychloroquine. She did not have further thrombotic events, and the acute kidney injury completely resolved. ACL IgG antibodies decreased to normal levels, and repeated tests were negative. After 7 years, anticoagulation and immunosuppressive drugs were discontinued. During a follow‐up of 24 months, she remained in complete clinical remission. This report highlights the occurrence of autoimmune disorders induced by TNFi. Thus, careful monitoring of adverse immune reactions to TNFi is highly recommended. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Tofacitinib and aminosalicylic acid (5‐ASA) are commonly used to treat ulcerative colitis (UC). However, evidence on the effect of concomitant 5‐ASA use in patients receiving tofacitinib is limited. This study investigated the effects of 5‐ASA combined with tofacitinib in UC patients.This retrospective cohort study used data from the Medical Data Vision database, including patients with UC treated with tofacitinib from May 2018 to April 2022. Patients were grouped according to tofacitinib dosage and assessed for the efficacy of concomitant 5‐ASA use. The primary endpoint was clinical relapse.A total of 1213 patients with UC were included in the analysis, with 416 in the 5 mg BID group and 797 in the 10 mg BID group. In the 5 mg BID group, the cumulative relapse‐free rate was significantly higher in patients receiving concomitant 5‐ASA (P < 0.0001). Multivariate Cox regression analysis confirmed that concomitant 5‐ASA use significantly reduced the risk of clinical relapse (adjusted hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.31–0.70). In the 10 mg BID group, no significant difference was noted in the cumulative relapse‐free rate between patients treated with and without 5‐ASA (P = 0.445). Similarly, multivariate Cox regression analysis indicated that concomitant 5‐ASA use did not significantly affect relapse risk (adjusted HR, 0.97; 95% CI, 0.71–1.32).Concomitant 5‐ASA use reduced the risk of relapse in patients on 5 mg tofacitinib BID, suggesting benefits at lower doses. However, no significant benefit was observed with 5‐ASA use in those 10 mg tofacitinib BID. [ABSTRACT FROM AUTHOR]

Introduction: Scutellarein (Scu) is a natural occurring flavonoid found in multiple traditional Chinese medicines such as Oroxylum indicum (L.) Kurz and Scutellaria baicalensis , with various pharmacological activities including anti-inflammation, anti-oxidation and myocardial protection. Here, we investigated the therapeutic efficacy of Scu on ulcerative colitis (UC) and the underlying mechanism. Methods: Efficacy of Scu on UC was evaluated in dextran sulfate sodium (DSS) induced colitis mouse model. Inflammation in colonic tissues was assessed by myeloperoxidase activity assay and RT-qPCR. Barrier proteins expression was examined using immunostaining and Western blot. IL-1β-treated HT-29 cells was used for mechanical investigation. Results: Gavage of Scu significantly decreased the DAI score, improved colon shortening, ameliorated the pathological score in DSS-treated mice with better efficacy than the positive drug, 5-aminosalicylic acid. Scu also inhibited the expression levels of cytokines (Il-1β , Tnf-α , Il-1α , Il-6 , and Cxcl1) as well as barrier proteins (E-cadherin, Occludin, and ZO-1) in colon tissues of DSS mice. In intestinal epithelial HT-29 cells, Scu attenuated the IL-1β-downregulated expression levels of E-cadherin, occludin, and ZO-1, while reduced IL-1β-upregulated IL-6 and IL-8 mRNA levels. Moreover, Scu inhibited the phosphorylation and nuclear translocation of NF-κB and suppression of NF-κB phosphorylation abolished IL-1β-disrupted epithelial barrier integrity and IL-1β-upregulated proinflammatory mediators expression in HT-29 cells. Conclusion: These data demonstrate that Scu is an efficacious therapeutic agent to treat UC. Inhibition of inflammatory responses and maintenance of epithelial barrier integrity through NF-κB signaling pathway underlines Scu therapeutic effect on UC. [ABSTRACT FROM AUTHOR]

Introduction: Observational studies have discovered a contradictory phenomenon between Helicobacter pylori (H. pylori) infection and inflammatory bowel disease (IBD). The study aimed to confirm the causal association between H. pylori and IBD, including ulcerative colitis (UC) and Crohn's disease (CD). Methods: We conducted a Mendelian randomization (MR) study with two sample Genome-Wide Association Studies (GWAS) to determine whether there is a causal relationship between H. pylori infection and IBD, as well as the possible pathogenic factors that may be involved. The reliability of the main MR assumptions was examined through a series of sensitivity analyses. Results: Two genetic variants (SNPs) previously identified were employed as instrumental variables (IVs) for H. pylori infection. GWAS data for IBD, UC, and CD were obtained from the recent DF10 release10 of the FinnGen study. Our findings indicated a significant association between H. pylori seropositivity and an increased risk of IBD and UC (IBD: OR: 1.16, 95% CI, 1.03–1.31, P < 0.05; UC: OR: 1.22, 95% CI, 1.08–1.37, P < 0.001) while no causal relationship with CD (P > 0.05). Analysis of the main virulence pathogenic factors revealed a causal relationship between cytotoxin-associated protein A (CagA) and IBD and UC (IBD: OR: 1. 06, 95% CI, 1.001–1.11, P < 0.05; UC: OR: 1.07, 95% CI, 1.004–1.14, P < 0.05), while no correlation was found for vacuolar cytotoxin A (VacA) (P > 0.05). After applying the False Discovery Rate (FDR) correction, the causal relationship between CagA and the risk of IBD or UC was no longer statistically significant. Conclusion: This study suggests a potential causal relationship between H. pylori infection and IBD, particularly UC. The effect may be more pronounced in individuals with previous H. pylori infections. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study is to compare different information retrieval methods that can be used to identify utility inputs for health economic models. Methods: The usual practice of using systematic review methods was compared with two alternatives (iterative searching and rapid review), using a health technology assessment (HTA) case study in ulcerative colitis (UC). We analysed whether there were differences in the utility values identified when using the alternative search methods. Success was evaluated in terms of time, burden and relevance of identified information. The identified utility values were tested in an executable health economic model developed for UC, and the model results were compared. Results: The usual practice of using systematic review search approaches identified the most publications but was also the least precise method and took longest to complete. The inclusion of data from the different search methods in the model did not lead to different conclusions across search methods. Conclusions: In this case study, usual practice was less efficient and resulted in the same health economic model conclusions as the alternative search methods. Further case studies are required to examine whether this conclusion might be generalisable. [ABSTRACT FROM AUTHOR]

Background: Overlapping clinical manifestations of irritable bowel syndrome (IBS) and IBS-like symptoms in patients with inflammatory bowel disease (IBD-IBS) present challenges in diagnosis and management. Both conditions are associated with alterations in metabolites, but few studies have described the lipid profiles. Our aim was to pinpoint specific lipids that contribute to the pathogenesis of IBS and IBD-IBS by analyzing multiple biologic samples. Methods: Diarrhea-predominant IBS (IBS-D) patients (n = 39), ulcerative colitis in remission with IBS-like symptoms patients (UCR-IBS) (n = 21), and healthy volunteers (n = 35) were recruited. IBS-D patients meet the Rome IV diagnostic criteria, and UCR-IBS patients matched mayo scores ≤ two points and Rome IV diagnostic criteria. Serum, feces, and mucosa were collected for further analysis. Lipid extraction was carried out by ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Results: Lipidomics of mucosa and serum samples significantly differed among the three groups. Feces showed the most altered lipid species, and the enrichment analysis of 347 differentially abundant metabolites via KEGG pathway analysis revealed that alpha-linolenic acid metabolism was significantly altered in the two groups (P < 0.01). The ratio of omega-6/omega-3 fatty acid were imbalance in serum samples. Conclusions: This study revealed a comprehensive lipid composition pattern between IBS-D patients and UCR-IBS patients. We found several distinctive lipids involved in alpha-linolenic acid metabolism, reflecting an imbalance in the omega-6/omega-3 fatty acid ratio. Compared to mucosa and serum samples, fecal samples might have more advantages in lipidomics studies due to the convenience of sample collection and effectiveness in reflecting metabolic information. [ABSTRACT FROM AUTHOR]

Background and Aims: Subcutaneous (SC) formulations of infliximab (IFX) and vedolizumab (VDZ) are approved for the treatment of inflammatory bowel diseases (IBDs). Our aim was to evaluate the effectiveness of switching from intravenous (IV) to SC formulations of IFX and VDZ in IBDs. Methods: This multicentre, retrospective study collected data of adult patients with Crohn's disease (CD) or ulcerative colitis (UC) switched to SC IFX or VDZ. The primary endpoint was clinical remission at 12 months stratified based on timing of switch. A composite endpoint consisting of therapy discontinuation, reverse‐switch, need for steroids, and drug optimization was evaluated. A multivariate analysis investigated the association between patients' characteristics and outcomes. Results: Two hundred and thirty‐one patients (59% UC, 53% male, mean age 44 ± 15 years, 68% IFX) from 13 centres were included. The switch occurred at Week 6 in a third of cases (36%). Median time to switch was 13 months. Most patients switched to SC IFX and VDZ were in clinical remission at 3 (87% and 77%), 6 (86% and 83%) and 12 (63% and 60%) months. In the multivariate analysis, there was no difference in clinical remission rate at 12 months; however, patients switched at Week 6 had a higher rate of experiencing any therapeutic changes at 3 (false discovery rate (FDR) =.002), 6 (FDR <1 × 10−10) or 12 months (FDR =.08). Clinical disease activity at baseline (only in UC) (FDR =.07) and previous exposure to biologics (FDR =.001) were risk factors for composite endpoint at 6 and 12 months. Conclusion: SC IFX and VDZ are effective in daily clinical practice in IBD patients. Switching patients in remission reduces the risk of negative outcomes. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), poses a significant challenge to health care systems because of its chronic nature and increasing global prevalence. Effective management of IBD requires accurate diagnostic tools and biomarkers. This systematic review and meta‐analysis aimed to evaluate the relationship between bilirubin concentrations and IBD activity and outcomes. Methods: A comprehensive search of electronic databases identified 11 studies that included 2606 subjects with IBD and 3607 healthy controls. Results: Bilirubin concentrations were significantly lower in subjects with IBD when compared to controls (SMD = −0.96, 95% CI −1.21 to −0.70; p <.001). Although substantial heterogeneity was observed, sensitivity analysis confirmed the robustness of the results. Publication bias was detected, but subgroup analyses did not significantly alter the results. Meta‐regression showed that age was a significant factor influencing the association between bilirubin concentrations and IBD. Subgroup analyses showed a more pronounced reduction in bilirubin concentrations in subjects with CD than those with UC. Conclusion: This study supports the potential utility of bilirubin as a biomarker in IBD, emphasizing the need for further research to validate its clinical significance. [ABSTRACT FROM AUTHOR]

The global burden of Inflammatory bowel disease (IBD) has been rising over the last decades. IBD is an intestinal disorder with a complex and largely unknown etiology. The disease is characterized by a chronically inflamed gastrointestinal tract, with intermittent phases of exacerbation and remission. This compromised intestinal barrier can contribute to, enhance, or even enable the toxicity of drugs, food-borne chemicals and particulate matter. This review discusses whether the rising prevalence of IBD in our society warrants the consideration of IBD patients as a specific population group in toxicological safety assessment. Various in vivo, ex vivo and in vitro models are discussed that can simulate hallmarks of IBD and may be used to study the effects of prevalent intestinal inflammation on the hazards of these various toxicants. In conclusion, risk assessments based on healthy individuals may not sufficiently cover IBD patient safety and it is suggested to consider this susceptible subgroup of the population in future toxicological assessments. [ABSTRACT FROM AUTHOR]

Background: Kidney function can be impaired in patients with inflammatory bowel diseases (IBD), including Crohn's diseases (CD) and ulcerative colitis (UC). However, the causal relationship between IBD and chronic kidney diseases (CKD) remains unclear. Methods: We determined the causal association between IBD and CKD by performing two‐sample bidirectional mendelian randomization (MR) analyses. Independent genetic variants were selected as instrumental variables (IVs) of the exposure from open‐access genome‐wide association studies (GWAS) among European ancestry. IVs–outcome estimates were extracted from three separate GWAS for IBD and two for CKD, respectively. Inverse‐variance‐weighted model was used as the primary MR method. The pleiotropic effect and heterogeneity were evaluated. For either direction, analyses were performed per outcome database and were subsequently meta‐analysed. Results: Genetically predicted IBD was associated with higher risk of CKD (OR: 1.045, 95% CI: 1.016–1.073, P = 0.002) by including 42 344 IBD cases and 229 164 controls. Further analyses showed genetic liability to CD increased the risk of CKD (OR: 1.057, 95% CI: 1.027–1.087, p < 0.001) whereas UC did not (OR: 0.999, 95% CI:0.969–1.031, p = 0.970). In contrast, genetically predicted CKD was not associated with IBD (OR: 1.010, 95% CI: 0.965–1.056, p = 0.676), UC (OR: 1.011, 95% CI: 0.948–1.078, p = 0.746) and CD (OR: 1.024; 95% CI: 0.963–1.089, p = 0.447). Conclusions: We concluded that CD, but not UC, can increase the risk of CKD causally. CD, but not UC, can increase the risk of chronic kidney disease causally. These findings enhance our understanding of the differential impact of IBD subtypes on CKD. It may be necessary to monitor kidney function regularly in patients with CD. Summary at a Glance: Crohn's diseases, but not ulcerative colitis, can increase the risk of chronic kidney diseases (CKD) causally.CKD were not associated with the risk of inflammatory bowel diseases casually. [ABSTRACT FROM AUTHOR]

Aim(s): This article explores the application of mesalazine-loaded nanoparticles (MLZ-NPs) encapsulated in Abelmoschus esculentus plant polysaccharide-based pellets (MLZ-NPs-Pellets) for ulcerative colitis. Methods: MLZ-NPs were prepared and evaluated for diameter, PDI, and entrapment efficiency. In-vitro efficacy study was conducted on Caco-2 cells. MLZ-NPs were encapsulated in polysaccharides to form MLZ-NPs-Pellets and characterised for efficacy in animals and targeting efficiency in human volunteers. Results: Optimised batch of MLZ-NPs were characterised for diameter, PDI, zeta potential and entrapment efficiency which was found to be 145.42 ± 6.75 nm, 0.214 ± 0.049, −31.63 mV and 77.65 ± 2.33(%w/w) respectively. ROS, superoxide and NF-kβ were well controlled in Caco-2 cells when treated with MLZ-NPs. In-vivo data revealed that some parameters (body weight, colon length, lipid peroxidase, and glutathione) recovered significantly in the DSS-induced mice model treated with oral MLZ-NPs-Pellets. Gamma scintigraphy revealed that the formulation can effectively target the colon within 600 min. Conclusion: MLZ-NPs-Pellets can be effectively used for microbial-triggered colon targeting approach in treating ulcerative colitis. [ABSTRACT FROM AUTHOR]

Organic nanocrystals, particularly those composed of conjugated molecules, hold immense potential for various applications. However, their practical utility is often hindered by the challenge of achieving stable aqueous dispersions, which are essential for biological compatibility and effective delivery. This study introduces a novel and versatile strategy for preparing stable aqueous organic nanocrystals using a modified reprecipitation method. We demonstrate the broad applicability of this approach by successfully preparing a diverse library of nanocrystals from 27 conjugated molecules. Our findings reveal a charge-balanced aggregation mechanism for nanocrystal formation, highlighting the crucial role of surface charge in controlling particle size and stability. Based on this mechanism, we establish a comprehensive molecular combination strategy that directly links molecular properties to colloidal behaviour, enabling the straightforward prediction and preparation of stable aqueous dispersions without the need for excipients. This strategy provides a practical workflow for tailoring the functionality of these nanocrystals for a wide range of applications. To illustrate their therapeutic potential, we demonstrate the enhanced efficacy of these nanocrystals in treating acute ulcerative colitis, myocardial ischemia/reperfusion injury, and cancer in mouse models. This work paves the way for developing next-generation nanomaterials with tailored functionalities for diverse biomedical applications. [Display omitted] • Bridging Disciplines: This research bridges crystal engineering and colloid science by achieving aqueous stability of organic nanocrystals. • New Design Rules: Charge-balanced aggregation links molecular properties to colloidal behaviour for stable nanocrystals. • Predictive Strategy: A strategy for identifying suitable molecular combinations for aqueous organic nanocrystals. • Practical Workflow: A practical workflow for preparing diverse aqueous organic nanocrystals. • Functional Control & Applications: Diverse molecular combinations enable control over nanocrystal functionality for bioapplications. [ABSTRACT FROM AUTHOR]

Summary: Background: Several new treatments including small molecules and biologics have been approved for the treatment of inflammatory bowel diseases in recent years. Clinicians and patients now have a wide variety of therapeutic options to choose from and these novel therapies provide several advantages including oral administration, lower immunogenicity, better selectivity and arguably better safety profiles. An increase in treatment options has increased the complexity of decision‐making. Both patients and clinicians have had to become rapidly familiar with efficacy of new medications balanced against a range of pre‐initiation requirements, dosing schedules and adverse event profiles. Aims: To provide a simple guide to practising clinicians on recently approved and emerging therapies and address key challenges around treatment strategies such as optimal sequencing and timing of treatment. Methods: We comprehensively searched the published literature and major conference abstracts to identify phase III placebo‐controlled and active comparator trials for Crohn's disease and ulcerative colitis. Results: Data for recently approved therapies including selective Janus kinase inhibitors, sphingosine‐1 receptor modulators and p19 interleukin (IL)‐23 inhibitors have demonstrated improved patient outcomes in both Crohn's disease and ulcerative colitis. Further comparative head‐to‐head studies have improved our understanding of when and how to optimally use newer therapies, specifically for IL‐23 inhibitors. Data for emerging treatment options and novel treatment strategies such as early effective treatment, combinations of treatments and implications for sequencing are continuing to transform IBD care continually. Conclusions: Recently approved novel therapies have expanded the range of medical options available to treat IBD. However, further data from long‐term extension studies, real‐world studies and head‐to‐head trials are warranted to better inform the long‐term safety and optimal sequencing of treatments for patients living with IBD. [ABSTRACT FROM AUTHOR]

Summary: Background: Inflammatory bowel disease (IBD) follows a heterogenous disease course and predicting a patient's prognosis is challenging. There is a wide burden of illness in IBD and existing tools measure disease activity at a snapshot in time. Comprehensive assessment of IBD severity should incorporate disease activity, prognosis, and the impacts of disease on a patient. This review investigates the concept of disease severity in adults with IBD to highlight key components contributing to this. Methods: To perform this narrative review, a Medline search was conducted for full‐text articles available at 1st March 2024 using search terms which encompassed disease activity assessment, disease severity, prognosis, natural history of Crohn's disease (CD) and ulcerative colitis (UC), and the burden of IBD. Results: Current methods of disease assessment in IBD have evolved from a focus on the burden of symptoms to one that includes inflammatory targets, genetic, serological, and proteomic profiles, and assessments of quality‐of‐life (QoL), disability, and psychosocial health. Longitudinal studies of IBD suggest that the burden of illness is driven by disease phenotype, clinical markers of complicated disease course (previous intestinal resection, corticosteroid use, perianal disease in CD, recent hospitalisations in UC), gut inflammation, and the impact of IBD on the patient. Conclusions: Disease severity in IBD can be difficult to conceptualise due to the multitude of factors that contribute to IBD outcomes. Measurement of IBD severity may better encapsulate the full burden of illness rather than gut inflammation alone at a single timepoint and may be associated with longitudinal outcomes. [ABSTRACT FROM AUTHOR]

Diallyl trisulfide (DATS), a sulphur‐containing compound isolated from the medicinal food plant garlic, has been previously reported to attenuate experimental colitis induced by either dextran sodium sulphate (DSS) or 2,4,6‐trinitrobenzenesulfonic acid (TNBS) in mice; however, the underlying mechanism remains to be identified. In this study, we deciphered the key mechanism by which DATS alleviates ulcerative colitis (UC). We showed that oral administration of DATS for 10 consecutive days greatly restrained the infiltration of macrophages and the pathological changes in colonic tissues of mice with DSS‐induced colitis. DATS treatment notably dampened the content of IL‐1β and IL‐18 and suppressed NLRP3 inflammasome activation in colon. Mechanistically, DATS effectively diminished the generation of ROS in macrophages. The suppressive effect of DATS on the activation of NLRP3 inflammasome and downregulation of IL‐18 and IL‐1β levels was blunted by xanthine oxidase. Further studies revealed that DATS inhibited NF‐κB pathway activation by suppressing the expression of Trx‐1, thereby inhibiting NLRP3 inflammasome activation. Trx‐1 overexpression and interference in macrophages promoted and diminished NLRP3 inflammasome activation, respectively. In summary, garlic and its main active ingredient DATS have potentials to prevent and treat UC, and DATS functions by inhibiting NLRP3 inflammasome activation via Trx‐1/ROS pathway. [ABSTRACT FROM AUTHOR]

Background: Crohn's disease (CD) and ulcerative colitis (UC) are prevalent in adult and pediatric populations, but their differences are not well studied using national data. We compared the clinical outcomes of these patients using the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) databases.Methods: Colectomy cases for CD and UC, the 2 major forms of inflammatory bowel disease (IBD), were compared between adult and pediatric patients using the 2017-2019 ACS NSQIP databases. Various clinical factors were analyzed, with postoperative complications being the primary outcome of interest.Results: We identified 542 pediatric and 5174 adult CD patients and 360 pediatric and 1292 adult UC patients. Adults with CD or UC were more likely to be on steroids preoperatively (CD: 60.15% vs 24.54%; UC: 65.63% vs 51.39%). Children with IBD were more likely to have preoperative transfusions (CD: 1.48% vs .33%; UC: 8.33% vs .62%), systemic inflammatory response syndrome (CD: 3.51% vs .93%; UC: 12.78% vs 3.10%), or sepsis (CD: 1.85% vs .66%; UC: 1.39% vs .31%). Unplanned reoperations were more common among pediatric patients in both disease states compared to adults (CD: 6.27% vs 4.10%; UC: 11.11% vs 4.26%), with P-values for all factors described as ≤.02. Multivariate logistic regression found pediatric age to be associated with higher odds of needing a reoperation among UC patients but not CD patients.Conclusion: Pediatric patients were sicker at the time of surgery, and those with either disease were more likely to require a reoperation within 30 days. [ABSTRACT FROM AUTHOR]

Purpose: To study the risk for eye diseases in individuals with Ulcerative Colitis (UC), and to assess whether silica dust‐exposure could contribute to the development of inflammatory eye diseases. Methods: A case–control study was conducted using a patient register processed by the National Board of Health and Welfare (NBHW) and Statistics Sweden. Cases were diagnosed with UC between 2007 and 2016. Matching was done with two random controls having the same age, sex and county of residence, without a systemic inflammatory disease. Using a job‐exposure matrix, cases and controls were assessed for work‐related silica dust exposure. The risk for eye disease was estimated by Cox regression analysis with calculation of Hazard Ratio (HR). Results: A total of 58 989 individuals were included, comprising 19 663 cases and 39 326 controls. The sex distribution was similar. Overall, individuals with UC had an increased risk for eye disease, specified in ICD 10 chapter VII (H00‐H59) with HR 1.25 (CI 1.20–1.32). The highest HR on block‐level for cases was 1.52 (CI 1.36–1.70), (H15‐H22), which includes episcleritis, keratitis and anterior uveitis. The risk for ocular disease was higher in silica dust‐exposed than non‐exposed with a HR of 1.44 (CI 1.16–1.78) and 1.25 (CI 1.19–1.31), respectively. Among cases, the risk for iridocyclitis (H20) was further elevated by silica dust exposure, with HR of 3.84 (CI 1.64–8.97) in exposed compared to 1.94 (1.57–2.41) in non‐exposed. Conclusion: UC is associated with an increased risk for eye diseases, including inflammatory conditions. Our findings highlight that silica dust‐exposure may be of importance in the pathogenesis of uveitis. [ABSTRACT FROM AUTHOR]

Ulcerative colitis has been associated with psychological distress and an aberrant immune response. The immunomodulatory role of systemic cytokines produced during experimental intestinal inflammation in tonic immobility (TI) defensive behavior remains unknown. The present study characterized the TI defensive behavior of guinea pigs subjected to colitis induction at the acute stage and after recovery from intestinal mucosa injury. Moreover, we investigated whether inflammatory mediators (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-8, IL-10, and prostaglandins) act on the mesencephalic nucleus, periaqueductal gray matter (PAG). Colitis was induced in guinea pigs by intrarectal administration of acetic acid. The TI defensive behavior, histology, cytokine production, and expression of c-FOS, IBA-1, and cyclooxygenase (COX)-2 in PAG were evaluated. Colitis reduced the duration of TI episodes from the first day, persisting throughout the 7-day experimental period. Neuronal c-FOS immunoreactivity was augmented in both columns of the PAG (ventrolateral (vlPAG) and dorsal), but there were no changes in IBA-1 expression. Dexamethasone, infliximab, and parecoxib treatments increased the duration of TI episodes, suggesting a modulatory role of peripheral inflammatory mediators in this behavior. Immunoneutralization of TNF-α, IL-1β, and IL-8 in the vlPAG reversed all effects produced by colitis. In contrast, IL-10 neutralization further reduced the duration of TI episodes. Our results reveal that peripherally produced inflammatory mediators during colitis may modulate neuronal functioning in mesencephalic structures such as vlPAG. [ABSTRACT FROM AUTHOR]

The disorder of group 3 innate lymphoid cells (ILC3) subgroup, such as the predominance of NCR-ILC3 but the depletion of NCR+ILC3, is unfavorable to damaged intestinal barrier repair, which leads to the prolongations and obstinacy of ulcerative colitis (UC). Our previous studies had shown that luteolin promoted NCR−ILC3 differentitating into NCR+ILC3 to improving the depletion of NCR+ILC3 in UC mice, while the mechanism is unclear. This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR+ILC3. UC mice model was established with 2% DSS and Notch signaling was blocked, then luteolin was used to intervene. The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice, including inhibiting the weight loss, reducing the pathological damage of colon mucosa, etc. , was diminished with blocking Notch signaling pathway. In addition, luteolin increased the proportion of NCR+ILC3, NCR+MNK3 and IL-22+ILC3, decreased intestinal permeability, promoted mucin secretion, and promoted ZO-1 and Occludin expression, the above effect of luteolin was neutralized by Notch inhibitor LY-411575. Luteolin activated the abnormally blocked Notch signaling pathway in UC mice. And molecular docking predicted the affinity of luteolin for RBPJ to be −7.5 kcal·mol−1 in mouse, respectively; the affinity of luteolin for Notch1 and RBPJ was respectively scored to be −6.4 kcal·mol−1 and −7.7 kcal·mol−1 homo sapiens. These results proved that luteolin is positive for enhancing the proportion of NCR+ILC3 via Notch signaling, and it provides a basis for targeting NCR+ILC3 for restoring intestinal barrier function to alleviating ulcerative colitis. [ABSTRACT FROM AUTHOR]

Purpose: Interest in the quality of life (QoL) of patients with inflammatory bowel disease (IBD) has recently increased. Although measurement tools have been devised for IBD in general, there is no specific tool for measuring the QoL of patients with ulcerative colitis (UC). Therefore, we developed a QoL questionnaire specifically for patients with UC. Materials and Methods: The Korean Ulcerative Colitis-Specific Questionnaire (K-UCSQ) was developed through item generation, raw-scale construction, focus group meetings, and multi-center field tests. Two hundred patients with UC were recruited for a field test of the K-UCSQ, and subsequent responses to the Inflammatory Bowel Disease Questionnaire (IBDQ) were also obtained. After performing factor analyses to ensure construct validity, the K-UCSQ was finalized as a four-domain, 28-item questionnaire. Subsequent analyses evaluated the reliability of the K-UCSQ in terms of Cronbach’s alpha, concurrent validity in comparison with the pre-established IBDQ, and predictive validity of the area under the ROC curve (AUC) for clinically relevant QoL outcomes. Results: A Cronbach’s alpha of 0.94 showed excellent reliability. Furthermore, correlation analyses demonstrated the concurrent validity of the K-UCSQ in comparison with the IBDQ. The K-UCSQ also showed high validity in predicting the perceived overall health (AUC of 0.812 vs. 0.797 using the IBDQ) and past 2-week QoL (AUC of 0.864 vs. 0.859 using the IBDQ). Conclusion: The newly developed K-UCSQ is concise, bathroom problem-emphasizing, and UC-specific, suggesting that it could be a valid and reliable UC-specific instrument for QoL measurement. [ABSTRACT FROM AUTHOR]

Endoscopic scoring systems evaluate the severity of inflammation and provide objectivity, uniformity, and standardization of reporting of mucosal appearances in patients with inflammatory bowel disease; thus, they have been advised for assessing the efficacy of medical treatment and prognosis. This American Gastroenterological Association (AGA) Clinical Practice Update Expert Commentary aims to review the utilized endoscopic scoring systems and their role in assessing mucosal healing in inflammatory bowel disease and the practical challenges in their applications, as well as to discuss the future of endoscopic scoring systems. This expert commentary was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This expert commentary incorporates essential studies in this field and reflects the authors' expertise in the endoscopic evaluation of inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

The impact of patient sex on the presentation of inflammatory bowel disease (IBD) has been poorly evaluated. Our aims were to assess potential disparities in IBD phenotype and progression between sexes. We performed an observational multicenter study that included patients with Crohn's disease (CD) or ulcerative colitis from the Spanish Estudio Nacional en Enfermedad Inflamatoria intestinal sobre Determinantes genéticos y Ambientales registry. Data extraction was conducted in July 2021. A total of 51,595 patients with IBD were included, 52% were males and 25,947 had CD. The median follow-up period after diagnosis was 9 years in males and 10 years in females. In CD, female sex was an independent risk factor for medium disease onset (age, 17–40 y) (relative risk ratio, 1.45; 95% CI, 1.31–1.62), later disease onset (age, >40 y) (relative risk ratio, 1.55; 95% CI, 1.38–1.73), exclusive colonic involvement (odds ratio, 1.24; 95% CI, 1.14–1.34), inflammatory behavior (odds ratio, 1.14; 95% CI, 1.07–1.21), and extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.38–1.59). However, female sex was a protective factor for upper gastrointestinal involvement (odds ratio, 0.84; 95% CI, 0.79–0.90), penetrating behavior (odds ratio, 0.76; 95% CI, 0.70–0.82), perianal disease (odds ratio, 0.77; 95% CI, 0.71–0.82), and complications (odds ratio, 0.73; 95% CI, 0.66–0.80). In ulcerative colitis, female sex was an independent risk factor for extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.26–1.61). However, female sex was an independent protective factor for disease onset from age 40 onward (relative risk ratio, 0.76; 95% CI, 0.66–0.87), left-sided colonic involvement (relative risk ratio, 0.72; 95% CI, 0.67–0.78), extensive colonic involvement (relative risk ratio, 0.59; 95% CI, 0.55–0.64), and abdominal surgery (odds ratio, 0.78; 95% CI, 0.69–0.88). There is sexual dimorphism in IBD. The patient's sex should be taken into account in the clinical management of the disease. [Display omitted] [ABSTRACT FROM AUTHOR]

This meta-analysis aimed to ascertain whether small molecule drugs increase the risk of infection or malignancy in adult IBD patients. A comprehensive search of eight databases was conducted from their inception to November 2023. The risk of infections or malignancies in adult IBD patients treated with JAK inhibitors and S1P receptor modulators was compared. Fixed-effects or random-effects models were performed, and relative risk (RR) and 95 % confidence interval (CI) were calculated. 27 RCTs from 14 studies were included (n = 10,623). The evidence indicates that small molecule drugs increase the risk of any infections (RR: 1.23, 95 %CI: 1.05–1.44) and herpes zoster (RR: 2.23, 95 %CI: 1.39–3.57). Specifically, UC patients on Filgotinib and Tofacitinib, and CD patients on Upadacitinib, showed elevated risks of any infections (RR: 1.27, 95 % CI: 1.04–1.56; RR: 1.42, 95 % CI: 1.16–1.75; RR: 1.57, 95 % CI: 1.11–2.22). CD patients on Upadacitinib also had a significantly higher risk of herpes zoster (RR: 2.64, 95 %CI: 1.16–5.99). No infections were associated with S1P receptor modulators, and similarly, no malignancies were linked to small molecule drugs. JAK inhibitors increase the risk of any infections and herpes zoster Over a one-year follow-up period in IBD patients. Continuous monitoring of their long-term safety is necessary. [ABSTRACT FROM AUTHOR]

Objective: Despite being reported safety, the advantages of transanal minimally invasive proctocolectomy (TAMIP) are controversial, and comparative studies on postoperative defecation function between ileal pouch‐anal anastomosis (IPAA) using laparoscopic transanal manipulation (TAMIP‐IPAA) and without this technique (traditional IPAA) are lacking. This study analyzed TAMIP's impact on short‐term and postoperative defecation function in patients with ulcerative colitis (UC) to evaluate its safety and feasibility. Methods: Inclusion criteria comprised patients with UC undergoing minimally invasive proctocolectomy at our hospital from May 2014 to May 2023. The TAMIP‐IPAA approach involved precise rectal mucosa removal while preserving the sphincter muscle during laparoscopic transanal manipulation. Results: In the evaluation of short‐term outcomes for 71 patients undergoing proctocolectomy, the TAMIP group (37 patients) outperformed the non‐TAMIP group in operative time (395 vs. 289 min, p < 0.001) and postoperative hospital stay (12 vs. 8 days, p < 0.001). Additionally, TAMIP‐IPAA demonstrated advantages over traditional IPAA (seven patients), in operative time (443 vs. 289 min, p = 0.006), intraoperative blood loss (392 vs. 130 mL, p = 0.001), postoperative hospital stay (18 vs. 8 days, p = 0.003), anastomotic leakage (42.9% vs. 8.1%, p = 0.041), and re‐admission within 30 days (57.1% vs. 8.1%, p = 0.009). Wexner scores were significantly superior in the TAMIP‐IPAA group at 6 months (14.5 vs. 8.0 points, p = 0.029) and 1 year post stoma closure (14.0 vs. 7.0 points, p = 0.020), indicating enhanced short‐term outcomes and defecation function compared to traditional IPAA. Conclusions: TAMIP‐IPAA for UC has the potential to offer promising benefits, including the enhancement of short‐term outcomes and the improvement of defecation function. [ABSTRACT FROM AUTHOR]

Introduction: Nocturia is a common symptom of lower urinary tract syndrome (LUTS). In previous studies, a close association between LUTS and colorectal inflammation has been reported. However, evidence regarding the association between nighttime urinary frequency and ulcerative colitis (UC) is limited. Herein, we investigated the association between nighttime urinary frequency and clinical outcomes of UC. Methods: We surveyed 287 Japanese patients with UC. A self‐administered questionnaire was used to collect the information on the variables studied. Patients were divided into three groups based on nighttime urinary frequency: (1) no voids, (2) one void, and (3) two or more voids. The assessment of clinical outcomes was based on mucosal healing (MH) and clinical remission (CR). The association between nighttime urinary frequency and prevalence of MH and CR was evaluated using multivariate logistic regression analyses. Results: The prevalence of one nighttime frequency and two or more nighttime frequency in this cohort was 35.5% and 26.8%, respectively. The percentage of MH and CR was 24.7% and 59.2%, respectively. Two or more nighttime frequency (adjusted odds ratio [OR]: 0.31, 95% confidence interval [CI]: 0.13–0.73) was independently and inversely associated with MH. In nonelderly patients (<70 years) and patients in CR, an association between two or more nighttime frequency and MH remained significant (non‐elderly: adjusted OR: 0.27, 95% CI: 0.09–0.72 and only CR: adjusted OR: 0.34, 95% CI: 0.12–0.90). Conclusion: Nighttime urinary frequency was independently and inversely associated with MH in Japanese patients with UC. Nighttime urinary frequency may serve as a complementary physical sign of MH in patients with UC. [ABSTRACT FROM AUTHOR]

Objective: To review the pharmacologic and clinical profile of mirikizumab in the treatment of moderate to severe ulcerative colitis (UC). Data sources: A PubMed search was performed from inception to December 2023 using keywords mirikizumab, interleukin-23 inhibitor, and UC. Information was also obtained from package inserts as well as published abstracts. Study selection and data extraction: Phase 3 studies plus relevant literature on mirikizumab pharmacologic and clinical profile were reviewed. Data synthesis: Mirikizumab approval was based on LUCENT-1 and LUCENT-2. In the phase 3 studies involving patients with moderate to severe UC, mirikizumab, when compared to placebo, resulted in clinical remission in a significantly higher proportion of patients in both the induction and maintenance phase. In addition, mirikizumab met the secondary endpoints of alternate definition of clinical remission, endoscopic remission, glucocorticoid-free clinical remission, histologic-endoscopic mucosal remission, and improvement in bowel urgency status, bowel-urgency remission, and maintenance of clinical remission. Common adverse events noted include infection (15.1%), injection-site reaction (8.7%), nasopharyngitis (7.2%), and headache (3.3%). Relevance to patient care and clinical practice in comparison to existing agents: Mirikizumab is the first selective interleukin 23 (IL-23) inhibitor approved for UC. Additional studies are required to determine how to position mirikizumab in both biologic-naïve and biologic-experienced patients with moderate to severe UC. Conclusion: Mirikizumab provides a novel mechanism of action for the treatment of moderate to severe UC and is another welcomed treatment advance in the treatment arsenal, providing a more selective mechanism of action while maintaining a comparable safety profile. [ABSTRACT FROM AUTHOR]

Background: Clinicopathological differences exist between ulcerative colitis-associated colorectal cancer (UC-CRC) and sporadic colorectal cancer (S-CRC). However, differences in the prognosis remain controversial, and the reason for these differences remains unclear. We therefore assessed the differences between patients with UC-CRC and S-CRC. Patients and Methods: This was a matched-pair analysis of the clinicopathological characteristics and prognosis of patients with UC-CRC and S-CRC who underwent colorectal resection between January 2000 and December 2021 at two institutions. Patients were matched according to age, sex, date of surgery, tumor location, and Union for International Cancer Control (UICC) stage. Results: A total of 5992 patients underwent surgery for CRC at the two institutions, and 288 patients (48 with UC-CRC and 240 with S-CRC) were matched in this study. Patients with UC-CRC underwent more invasive surgery and had a longer operative time than those with S-CRC, but there was no marked difference in postoperative complications or perioperative mortality. Long-term outcomes showed a similar 5-year overall survival (OS) for UC-CRC and S-CRC (86.5% versus 88.8%, p = 0.742); however, in stage 3 patients, patients with UC-CRC had a poorer 5-year OS than those with S-CRC (51.4% versus 83.8%, p = 0.032). The first recurrence sites in stage 3 UC-CRC were peritoneal dissemination followed by the bones, while those in S-CRC were the liver and pulmonary system. Conclusions: Despite no significant differences in surgical outcomes, patients with UC-CRC had a poorer prognosis than those with S-CRC at stage 3. The recurrence patterns in UC-CRC differed from those in S-CRC, suggesting a possible prognostic difference. [ABSTRACT FROM AUTHOR]

Chronic systemic inflammation caused by diseases such as ulcerative colitis (UC) and Crohn's disease (CD) increases the risk of developing colorectal cancer (CRC). Recent evidence indicates that patients with UC are more susceptible to prostate cancer (PCa), and individuals with PCa may also be at a higher risk of developing CRC. However, these relationships are not well defined. A better understanding of this phenomenon could improve the identification of high-risk populations. In this study, we characterized these relationships with experiments using preclinical mouse models of dextran sulfate sodium (DSS)-induced colitis (DSS-UC) and DSS/azoxymethane (AOM)-induced CRC (DSS/AOM-CRC) in wild-type and conditional transgenic mice of PCa. We showed that DSS-induced UC was more severe in mice with PCa and resulted in the development of CRC in the absence of AOM. We further showed that PCa-free mice that developed DSS-induced UC also showed histological changes in the normal prostate that resembled proliferative inflammatory atrophy. Finally, we used immunohistochemical immune profiling to show that mice with PCa-induced chronic systemic inflammation accumulated Gr1+ myeloid cells in the normal colon and exposure to DSS further enriched these cells in active colitis regions and colon tumors. Our study provides evidence to support a link between systemic chronic inflammation and cancer. [ABSTRACT FROM AUTHOR]

Amauroderma rugosum (Blume and T. Nees) Torrend (Ganodermataceae) (A.rugosum) has been found to have anti-inflammatory ability in previous studies. The present study aimed to verify the therapeutic benefits of A.rugosum in the treatment of ulcerative colitis and to investigate its underlying mechanism of action. Acute experimental ulcerative colitis was induced by feeding the mice drinking water supplemented with dextran sodium sulfate (DSS). The findings indicated that the ethanolic extract of domesticated A.rugosum exhibited therapeutic efficacy comparable to Salazosulfapyridine (SASP) in mitigating clinical symptoms and the pathological score of the colon. Furthermore, A.rugosum exhibited the capacity to enhance the expression of tight junction (TJ) proteins, while concurrently decreasing the levels of TNF-ɑ and IL-6. A noteworthy finding is that it exhibited the capability to diminish the nuclear translocation of NF-κB p65. In conclusion, A.rugosum attenuates DSS-induced ulcerative colitis by enhancing intestinal barrier function and inhibiting mucosal inflammation. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Gut microbiome‐targeted therapies (MTTs), including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation (FMT), have been widely used in inflammatory bowel diseases (IBD), but the best MTTs has not yet been confirmed. We performed a network meta‐analysis (NMA) to examine this in ulcerative colitis (UC) and Crohn's disease (CD).We searched for randomized controlled trials (RCTs) on the efficacy and safety of MTTs as adjuvant therapies for IBD until December 10, 2023. Data were pooled using a random effects model, with efficacy reported as pooled relative risks with 95% CIs, and interventions ranked according to means of surfaces under cumulative ranking values.Thirty‐eight RCTs met the inclusion criteria. Firstly, we compared the efficacy of MTTs in IBD patients. Only FMT and probiotics were superior to placebo in all outcomes, but FMT ranked best in improving clinical response rate and clinical and endoscopic remission rate, and probiotics ranked second in reducing clinical relapse rate showed significant efficacy, while prebiotics ranked first showed nonsignificant efficacy. Subsequently, we conducted NMA for specific MTT formulations in UC and CD separately, which revealed that FMT, especially combined FMT via colonoscopy and enema, showed significant efficacy and was superior in improving clinical response and remission rate of active UC patients. As for endoscopic remission and clinical relapse, multistrain probiotics based on specific genera of Lactobacillus and Bifidobacterium showed significant efficacy and ranked best in UC. In CD, we found that no MTTs were significantly better than placebo, but synbiotics comprising Bifidobacterium and fructo‐oligosaccharide/inulin mix and Saccharomyces ranked best in improving clinical remission and reducing clinical relapse, respectively. Moreover, FMT was safe in both UC and CD.FMT and multistrain probiotics showed superior efficacy in UC. However, the efficacy of MTTs varies among different IBD subtypes and disease stages; thus, the personalized treatment strategies of MTTs are necessary. [ABSTRACT FROM AUTHOR]

Ulcerative colitis is a chronic pathology characterized by relapsing–remitting phases of intestinal inflammation. Additionally, some patients develop neuropsychiatric disorders, such as depression and anxiety, or cognitive deficits. We aimed to investigate whether the development of chronic colitis elicits memory, locomotion, and mood impairments. It further examined whether these impairments are influenced by the relapsing–remitting phases of the colitis or by sex. Here, we used a chronic colitis model in male and female rats, induced with sodium dextran sulfate, mirroring the phases of human ulcerative colitis. Our results revealed that the severity of colitis was slightly higher in males than females. Chronic colitis triggered motor and short‐term memory deficits and induced anxiety‐ and depression‐like behaviors that remained throughout the development of the disease. There are also sex differences under control or inflammatory conditions. Therefore, in both situations, females compared to males displayed: (i) slightly lower locomotion, (ii) increased anxiety‐like behaviors, (iii) similar depression‐like behaviors, and (iv) similar short‐term memory deficit. Additionally, under control conditions, the mRNA levels of IL‐1β, IL‐6, and TNF‐α were higher in the female hippocampus. In both sexes, when chronic colitis was established, the neuroinflammation was evidenced by increased mRNA levels of these three cytokines in the hippocampus and in the motor and prefrontal cortices. Interestingly, this neuroinflammation was slightly greater in males. In summary, we show that the development of chronic colitis caused persistent behavioral abnormalities, highlighting sex differences, and that could be a consequence, at least in part, of the increase in IL‐1β, IL‐6, and TNF‐α in the brain. [ABSTRACT FROM AUTHOR]

Introduction: Several current therapies for autoimmune diseases do not provide sustained remission. Therapies that focus on the restoration of homeostasis within the immune system (i.e., immune resolution) could overcome the limitations of current therapies and provide more durable remission. However, there is no established consensus on appropriate clinical trial designs and endpoints to evaluate such therapies. Therefore, we conducted a systematic literature review (SLR) focusing on five index diseases (asthma, atopic dermatitis, rheumatoid arthritis, systemic lupus erythematosus [SLE], and ulcerative colitis) to explore published literature on 1) expert opinion on immune-resolution outcomes that should be measured in clinical trials; and 2) quantification of immune resolution in previous clinical trials. Methods: The SLR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Embase and MEDLINE databases were systematically searched (2013–2023) for published English language articles. Conference proceedings (2020–2022) from American Academy of Dermatology, American College of Rheumatology, Digestive Disease Week, European Alliance of Associations for Rheumatology, and European Academy of Dermatology and Venereology were searched to include relevant abstracts. The study protocol was registered in PROSPERO (CRD42023406489). Results: The SLR included 26 publications on 20 trials and 12 expert opinions. Expert opinions generally lacked specific recommendations on the assessment of immune resolution in clinical trials and instead suggested targets or biomarkers for future therapies. The targets included thymic stromal lymphopoietin (TSLP) in asthma; T helper (Th)2 and Th22 cells and their respective cytokines (interleukin [IL]-4R and IL-22) in atopic dermatitis; inhibitory/regulatory molecules involved in T-cell modulation, and protein tyrosine phosphatase, non-receptor type 22 (PTPN22) in rheumatoid arthritis; low-dose IL-2 therapy in SLE; and pro-resolution mediators in ulcerative colitis and asthma. In the interventional studies, direct biomarker assessments of immune resolution were the number/proportion of regulatory T-cells (Treg) and the ratio Th17/Treg in SLE and rheumatoid arthritis; the number of T follicular helper cells (Tfh), Th1, Th2, Th17, and Th22 in atopic dermatitis, rheumatoid arthritis, and SLE; and mucosal proinflammatory gene signatures (tumor necrosis factor [TNF], interleukin 1 alpha [IL1A], regenerating family member 1 alpha [REG1A], IL8, interleukin 1 beta [IL1B], and leukocyte immunoglobulin-like receptors A [LILRA]) in ulcerative colitis. Several studies reported a statistically significant relationship between clinical remission and immune-resolution biomarkers, suggesting a link between T-cell homeostasis, cytokine production, and disease activity in autoimmune diseases. Discussion: Existing literature does not offer clear guidance on the evaluation of immune resolution in interventional studies. Further research and consensus are needed to assess a treatment’s ability to induce long-term remission or low disease activity [ABSTRACT FROM AUTHOR]

Objective: Ulcerative colitis (UC) and Hashimoto's thyroiditis frequently cooccur in patients with multiple autoimmune conditions, but the specific association between UC and hypothyroidism is unknown. We used Mendelian randomization (MR) methods to determine the causal relationship between UC and hypothyroidism. Methods: We obtained single nucleotide polymorphisms (SNPs) related to ulcerative colitis (UC) and hypothyroidism from genome-wide association studies (GWAS) available in the public database of the Integrated Epidemiology Unit (IEU). To assess the causal relationship between UC and hypothyroidism, we employed MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode methods. Sensitivity analyses were performed using Cochran's Q test, the horizontal pleiotropy test, and the leave-one-out (LOO) method to assess the reliability of the MR data. The genes corresponding to instrumental variables (IVs) were subjected to Gene Ontology (GO) functional annotation, Kyoto Encyclopedia of the Genome (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) analysis to explore the mechanisms behind the causal relationships at the gene level. Results: Forward MR analysis indicated that hypothyroidism was associated with an increased risk of UC (IVW: P = 0.02, OR = 9.71, 95% confidence interval (CI) = 1.36–69.46). In contrast, reverse MR did not demonstrate a causal relationship between UC and hypothyroidism (IVW: P = 0.53). Sensitivity analysis proved the reliability of the results. The PPI network revealed CD247, CD80, and STAT4 as central genes. GO and KEGG analyses revealed significant enrichment of the T cell, gamma interferon (IFN-γ), and programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways. Conclusion: Hypothyroidism was a risk factor for UC. The balance of T-cell differentiation played an important role in the process of hypothyroidism-induced UC, and IL-21 might be the key to finding a cure. Enrichment of PD-1/PD-L1 might attenuate inflammation by suppressing the immune action of T cells. [ABSTRACT FROM AUTHOR]

AbstractObjectivesMaterial and methodsResultsConclusionsColectomy and subsequent bowel reconstruction in women with ulcerative colitis (UC) is associated with decreased fertility, this survey aims to investigate possible reasons for this.Women with UC aged 18–44 years at colectomy 2000–2020 were identified and data were retrieved from the Swedish inflammatory bowel disease register (SWIBREG). Additional information was obtained using a study-specific questionnaire.The survey was completed by 214 (72.8%) out of 294 eligible women. Mean age at disease onset was 22.9 years (standard deviation 0.5). No reconstruction was made in 67 (31.3%) women, whereof 24 (35.8%) had a completion proctectomy. Reconstruction was performed with ileorectal anastomosis (IRA) in 66 (30.8%) women and ileal pouch anal anastomosis (IPAA) in 81 (37.9%). Included women had on average 1.67 children (95% confidence interval 1.53–1.81) at the end of follow-up. The desire to have children was negatively affected by disease onset (59.4%), colectomy (44.9%) and reconstruction (36.7%). Altogether, 39.4% estimated that they had fewer children and 9.5% restrained completely from having children because of the disease. Difficulties to conceive were reported by 36.5% including 18.9% who expressed that they could not conceive at all. Difficulties to conceive was more common after reconstruction with IPAA (Odds Ratio [OR] 5.54) than IRA (OR 2.57).A majority of women with UC and colectomy expressed that the disease affected their desire to have children, more often limiting the number of children than completely refraining. For childless patients, difficulties to conceive was more common than voluntary childlessness. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammation is a significant driver in the development of various diseases, including cancer. Colitis-associated colorectal cancer (CA-CRC) refers to the increased risk of colorectal cancer in individuals with chronic inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease. Methods: This narrative review examines the link between chronic inflammation and CA-CRC. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science, focusing on studies published between 2000 and 2024. Studies were selected based on relevance to the role of inflammation in CA-CRC, specifically targeting molecular pathways and clinical implications. Both clinical and mechanistic studies were reviewed. Conclusion: Sustained inflammation in the colon fosters a pro-tumorigenic environment, leading to the initiation and progression of CA-CRC. Prevention strategies must focus on controlling chronic inflammation, optimizing IBD management, and implementing regular screenings. Emerging therapies targeting key inflammatory pathways and immune responses, along with microbiome modulation, hold promise for reducing CA-CRC risk. Understanding these molecular mechanisms provides a path toward personalized treatment and better outcomes for patients with IBD at risk of colorectal cancer. [ABSTRACT FROM AUTHOR]

In this study, a dextran sodium sulfate‐induced ulcerative colitis model in C57BL/6 mice was used to explore the effect of acceptable daily intake (ADI) of aspartame on inflammation in colonic tissues. The effects of aspartame on the inflammatory state of the colon in mice were comprehensively evaluated by comparing the body weight, colon length/colon length index, splenic index, disease activity index (DAI) score, histological activity index (HAI) score, the expression levels of tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6, claudin‐3, and occludin, the infiltration characteristics of macrophage and neutrophil and the composition of the gut microbiota in the control group, aspartame group, ulcerative colitis model group, and aspartame + ulcerative colitis group. We demonstrated that, in a mouse model of dextran sulfate‐induced ulcerative colitis, ADI of aspartame caused a significant decrease in body weight, colon length/colon length index, DAI scores, and expression levels of the proteins claudin‐3 and occludin. Moreover, ADI of aspartame caused an increase in the splenic index, HAI scores, the levels of proinflammatory factors TNF‐α, IL‐1β, and IL‐6 both in intestinal tissue and serum and infiltration of macrophages and neutrophils in colon tissues. These results showed that ADI of aspartame promoted intestinal pathology and systemic inflammation in a mouse model of colitis. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Methods Results Conclusions Variant‐adapted COVID‐19 vaccines are recommended for patients with inflammatory bowel disease (IBD). However, many patients rely on pre‐existing immunity by original vaccines or prior infections.To assess whether such immunity sufficiently combats the highly immune‐evasive SARS‐CoV‐2 JN.1 variant.Utilising two longitudinal cohorts, we evaluated immunity against JN.1 induced by original vaccines (IBD: n = 98; healthy: n = 48), omicron breakthrough infection (IBD: n = 55; healthy: n = 57) or XBB.1.5‐adapted vaccines (IBD: n = 18). Neutralisation and anti‐receptor‐binding domain (RBD) IgG levels against wild‐type SARS‐CoV‐2 and JN.1 were assessed using multiplex immunoassays. Study outcomes were wild‐type and JN.1 neutralisation following three doses of original mRNA vaccines, stratified by immunosuppressive therapy (primary outcome), and JN.1 neutralisation following third‐dose breakthrough infection or a fourth dose of XBB.1.5‐adapted mRNA vaccines (secondary outcomes).Following original vaccines, JN.1 neutralisation was lower than wild‐type neutralisation in all study groups (healthy, anti‐TNF and non‐anti‐TNF; each p < 0.001); most individuals lacked JN.1 neutralisation (healthy: 97.9%; anti‐TNF: 98.3% and non‐anti‐TNF: 92.3%). Confounder‐adjusted multivariable modelling strongly associated anti‐TNF therapy with low levels of anti‐JN.1‐RBD IgG (fold‐change 0.48 [95% CI 0.39–0.59]). JN.1 neutralisation was similar in patients with or without breakthrough infection (anti‐TNF, non‐anti‐TNF; each p > 0.05); neutralisation failure was 100% despite breakthrough infection. XBB.1.5‐adapted vaccines enhanced JN.1 neutralisation (p < 0.001) and reduced neutralisation failure rates in patients with IBD (94.4% pre‐vaccination vs. 44.4% post‐vaccination; p = 0.003).Only variant‐adapted vaccines protect against emerging SARS‐CoV‐2 variants. Patients with IBD and healthy individuals without recent vaccination may lack protection against the JN.1 subvariant KP.3 which causes current COVID‐19 surges. [ABSTRACT FROM AUTHOR]

The complexity of the gastrointestinal system plays a crucial role in coordinating essential processes such as digestion, nutrient absorption, and waste elimination. inflammatory bowel diseases (IBD) pose significant treatment challenges due to their complex aetiology and varied symptoms. Conventional therapeutic approaches often involve pharmacological interventions, which may have side effects and limited efficacy. Photobiomodulation (PBM), also known as low-level light therapy, has emerged as a promising therapeutic or adjunctive alternative in the treatment of intestinal diseases. The search was conducted in the MEDLINE database via PubMed, SCOPUS, covering the period from 1990 to 2024. A total of 72 studies were selected, of which 9 focused on inflammatory bowel diseases IBD, including ulcerative colitis (UC) and Crohn's disease (CD). Among these studies, 1 was clinical protocol while eight experimental. The results showed that PBM has a significant positive effect in IBD studies in rats, with reduction of intestinal inflammation, improvement of mucosal integrity, and modulation of the immune response. However, no clinical studies were found necessary to obtain results and establish effective and safe treatment protocols. Nevertheless, PBM holds potential as a non-invasive and complementary therapeutic approach for managing IBD, offering new perspectives for the treatment of chronic intestinal diseases. Therefore, this brief review emphasizes the need to transition from preclinical research to clinical research on this topic and highlights the scarcity of clinical studies. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aims Methods Results Conclusion Childhood antibiotic use has been associated with inflammatory bowel disease (IBD), although the potential contribution of infection frequency remains uncertain.To explore the association between early‐life infections, antibiotics and IBD development.We used population‐based data from ABIS (Sweden) and MoBa (Norway) cohorts following children from birth (1997–2009) until 2021. Prospectively collected questionnaires identified infection frequency (any, gastrointestinal and respiratory) and antibiotics (any, penicillin and non‐penicillin) until age 3. IBD diagnosis required ≥ 2 records in national health registries. Cohort‐specific hazard ratios (aHR), adjusted for parental education, smoking and IBD were estimated and pooled using a random‐effects model. Antibiotic analyses were adjusted for infection frequency.There were 103,046 children (11,872 ABIS and 91,174 MoBa), contributing to 1,663,898 person‐years of follow‐up, during which 395 were diagnosed with IBD. The frequency of any infection at 0 to < 1 and 1 to < 3 years showed a pooled aHR of 1.01 (95% confidence interval [CI] = 0.96–1.07) and 1.00 (95% CI = 0.99–1.01) per additional infection for IBD. Adjusting for infections, any versus no antibiotics in the first year was associated with IBD (pooled aHR = 1.33 [95% CI = 1.01–1.76]). The aHR for additional antibiotic course was 1.17 (95% CI = 0.96–1.44), driven by penicillin (per additional course, aHR = 1.28 [95% CI = 1.02–1.60]). Although antibiotics at 1 to < 3 years did not show an association with IBD or Crohn's disease, non‐penicillin antibiotics were associated with ulcerative colitis (per additional course, aHR = 1.95 [95% CI = 1.38–2.75]).Early‐life antibiotic use was, a significant risk factor for childhood and early adult‐onset IBD, independent of infection frequency. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a debilitating inflammatory bowel disease characterized by intestinal inflammation, barrier dysfunction, and dysbiosis, with limited treatment options available. This study systematically investigates the therapeutic potential of a synbiotic composed of galactooligosaccharides (GOS) and Limosilactobacillus reuteri in a murine model of colitis, revealing that GOS and L. reuteri synergistically protect against intestinal inflammation and barrier dysfunction by promoting the synthesis of pentadecanoic acid, an odd-chain fatty acid, from Bacteroides acidifaciens. Notably, the synbiotic, B. acidifaciens, and pentadecanoic acid are each capable of suppressing intestinal inflammation and enhancing tight junction by inhibiting NF-κB activation. Furthermore, similar reduction in B. acidifaciens and pentadecanoic acid levels are also observed in the feces from both human UC patients and lipopolysaccharide-induced intestinal inflammation in pigs. Our findings elucidate the protective mechanism of the synbiotic and highlight its therapeutic potential, along with B. acidifaciens and pentadecanoic acid, for UC and other intestinal inflammatory disorders. Here, Yujun Wu and colleagues report that a synbiotic composed of galactooligosaccharides and Limosilactobacillus reuteri alleviates gut inflammation in animals by enriching pentadecanoic acid synthesis from Bacteroides acidifaciens, showing potential for treating ulcerative colitis. [ABSTRACT FROM AUTHOR]