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Abstract Background In inflammatory bowel disease (IBD) of humans, nutrient malabsorption can result in fat‐soluble vitamin deficiency, especially of vitamin D. In veterinary species, decreased concentrations of vitamin D are relatively common in dogs with chronic enteropathy (CE), but data on the status of other fat‐soluble vitamins (FSVs) is lacking. Objectives Determine the serum concentrations of retinol, vitamin D, and α‐tocopherol in dogs with CE compared with healthy dogs and compare clinical, clinicopathologic variables between CE and healthy dogs to detect associations with decreased FSVs concentrations. Animals Eighteen client‐owned dogs with CE and 33 healthy dogs. Methods Serum 25‐hydroxyvitamin D (25[OH]D), serum retinol and α‐tocopherol concentrations were compared between groups. Correlations and multiple regression modeling were used to examine the relationship between serum 25(OH)D, retinol, and α‐tocopherol concentrations and clinical and clinicopathological variables. Results Dogs with low serum albumin concentrations were more likely to have lower 25(OH)D concentrations than dogs with normal serum albumin concentration. Dogs with CE had higher serum concentrations of retinol, and variable α‐tocopherol concentrations. The cause of these dysregulated vitamin concentrations is unclear and requires further study. Conclusion and Clinical Importance Dogs with severe forms of CE should be monitored for decreased concentrations of 25(OH)D. Additional studies are needed to evaluate the clinical relevance and the possible benefit of vitamin D supplementation in these patients.

Abstract Carvacrol and thymol (CAT) have been widely recognized for their antimicrobial and anti‐inflammatory properties, yet their specific effects on colitis and the mechanisms involved remain insufficiently understood. This study establishes a causative link between CAT administration and colitis mitigation, primarily through the enhancement of Bifidobacterium pseudolongum abundance in the colon. This increase promotes the production of secondary bile acids, particularly hyodeoxycholic acid (HDCA) and 12‐ketodeoxycholic acid (12‐KCAC), which exert anti‐inflammatory effects. Notably, CAT does not alleviate colitis symptoms in germ‐free mice, indicating the necessity of gut microbiota. This research uncovers a novel regulatory mechanism where HDCA and 12‐KCAC inhibit colonic inflammation by reducing the expression of transmembrane guanylate cyclase 1A in the colonic epithelium. This downregulation elevates intracellular Ca2+ and cGMP levels, activating protein kinase G (PKG). Activated PKG subsequently suppresses the mTOR signaling pathway, thereby ameliorating dextran sulfate sodium (DSS)‐induced colonic damage. These findings highlight potential metabolites and therapeutic targets for preventing and treating colitis. Bifidobacterium pseudolongum, HDCA, and 12‐KCAC emerge as promising candidates for therapeutic interventions in colitis and related disorders characterized by impaired tight junction function.

Abstract Background and Aim Inflammatory bowel disease (IBD) is a progressive condition where ongoing inflammation in the gastrointestinal tract can lead to complications such as strictures, and fistulae. The long‐term outcomes of newly diagnosed patients under current medical therapy can be used to plan health service provision and guide patients. Methods Prospective population‐based data on all incident patients diagnosed with IBD in Canterbury was gathered in 2014 (n = 205). The medical records of these patients were followed for medication use, disease progression, hospitalization, surgery and mortality, in the 10 years since their diagnosis. Survival analysis and cox regression determined characteristics associated with earlier time to these outcomes. Results Medical records of 184 IBD patients were able to be retrieved. Immunomodulators were used by 62% and biologics by 35%; hospitalization occurred for 42% and surgery for 15%. Montreal phenotype progression occurred for 21 and 7% of the cohort died. Younger age at diagnosis hazard ratio (HR) 2.1 (95% confidence interval [CI] 1.1–4.0) and Crohn's disease HR 1.7 (95% CI 1.1–2.6) was associated with immunomodulator use. Younger age was also associated with biologic use HR 2.9 (95% CI 1.2–6.9). Male gender was associated with surgery HR 2.8 (95% CI 1.2–6.4). Perianal disease at diagnosis (14.7%) was associated with immunomodulator use HR 2.58 (95% CI 1.44–4.59) and Montreal phenotype progression HR 2.93 (95% CI 1.10–7.77). Conclusion In the 10 years since diagnosis disease progression and treatment escalation occurred for most of this population‐based cohort. Earlier intervention for patients with higher‐risk characteristics may improve long‐term outcomes reducing the burden on health systems.

Abstract Background Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, but the molecular mechanisms underlying IBD are incompletely understood. In this study, we explored the role and regulating mechanism of otubain 2 (OTUB2), a deubiquitinating enzyme, in IBD. Methods To study the function of OTUB2 in IBD, we generated Otub2–/– mice and treated them with dextran sulfate sodium (DSS) to induce experimental colitis. Bone marrow transplantation was performed to identify the cell populations that were affected by OTUB2 in colitis. The molecular mechanism of OTUB2 in signal transduction was studied by various biochemical methods. Results OTUB2 was highly expressed in colon‐infiltrating macrophages in both humans with IBD and mice with DSS‐induced experimental colitis. Colitis was significantly aggravated in Otub2–/– mice and bone marrow chimeric mice receiving Otub2–/– bone marrow. OTUB2‐deficiency impaired the production of cytokines and chemokines in macrophages in response to the NOD2 agonist muramyl dipeptide (MDP). Upon MDP stimulation, OTUB2 promoted NOD2 signaling by stabilizing RIPK2. Mechanistically, OTUB2 inhibited the proteasomal degradation of RIPK2 by removing K48‐linked polyubiquitination on RIPK2, which was mediated by the active C51 residue in OTUB2. In mice, OTUB2 ablation abolished the protective effects of MDP administration in colitis. Conclusion This study identified OTUB2 as a novel regulator of intestinal inflammation.

Abstract Efficient strategies for transforming Bacillus subtilis vegetative cells into spores (BtS transformation) are still limited, although they show promise for the treatment of inflammatory bowel disease (IBD). A novel, simple, and rapid photo‐induced BtS transformation mechanism is now presented that utilizes a novel aggregation‐induced emission luminogen (AIEgen) photosensitizer, triphenylamine‐benzothiadiazole‐pyridine‐p‐tolylboronic acid bromine salt (TBPBB), that generates reactive oxygen species (ROS) when exposed to light. The ROS selectively target and damage the membranes of Bacillus subtilis and trigger their transformation into spores. These spores demonstrate considerable promise for the effective treatment of IBD in a mouse disease model. Furthermore, the fluorescence signal generated by TBPBB can be used to directly visualize the recovery of damaged intestinal tissue. This is a valuable tool for monitoring the healing process and gaining insights into therapeutic efficacy. This study highlights the remarkable practical value of AIEgen‐induced BtS transformation for identifying, localizing, and visualizing the therapeutic outcomes of IBD treatments.

Abstract Inflammatory bowel disease (IBD) is a chronic and unspecific inflammatory disorder of the gastrointestinal tract, and current treatment options often fail to maintain long‐term remission. Studies have shown that propionate level is reduced in fecal samples from patients with IBD. Propionate can ameliorate IBD through intestinal epithelial cells and immune regulation, but its effects on the inflammatory microenvironment and macrophage differentiation have not been widely studied. To address this, we constructed an engineered propionate‐producing probiotic (EcNP3) to achieve sustained restoration of propionate levels in the gut and increase its bioavailability. DSS‐induced experimental intestinal inflammation model was used to evaluate the effect of EcNP3 on improving the intestinal mucosal barrier and increasing the proportion of anti‐inflammatory macrophages. It was found that EcNP3 exhibited a restorative effect on the depletion of peritoneal anti‐inflammatory macrophages (F4/80hiCD11bhi) and significantly improved the expression level of IL‐10. Simultaneously, the expression of IL‐1β, IL‐6, and CXCL1 was downregulated while inhibiting apoptosis of tissue‐resident macrophages ex vivo. Further investigation revealed that EcNP3 regulates IL‐10 expression through G protein‐coupled receptor 43 and histone deacetylase. Furthermore, EcNP3 significantly inhibited the protein expression of HDAC1 and promoted the histone acetylation level of cells. Finally, EcNP3 significantly improved DSS‐induced colitis in mice by increasing mucus production and reducing inflammatory infiltration. Our results suggest that the engineered live biotherapeutic product EcNP3 is a safe and potently efficacious treatment for IBD, which defines a novel strategy in IBD therapy through macrophage IL‐10 signaling.

Abstract Colorectal cancer (CRC) and inflammatory bowel disease (IBD) are escalating global health concerns. Despite their distinct clinical presentations, both disorders share intricate genetic and molecular interactions. The Hippo signaling pathway plays a crucial role in regulating cell processes and is implicated in the pathogenesis of IBD and CRC. Circular RNAs (circRNAs) have gained attention for their roles in various diseases, including IBD and CRC. However, a comprehensive understanding of specific circRNAs involved in both IBD and CRC, and their functional roles is lacking. Here, it is found that circHIPK2 (hsa_circRNA_104507) is a bona fide circRNA consistently upregulated in both IBD and CRC suggesting its potential as a biomarker. Furthermore, silencing of circHIPK2 suppressed the growth of CRC cells in vitro and in vivo. Interestingly, decreased circHipk2 potentiated dextran sulfate sodium (DSS)‐induced colitis but alleviated colitis‐associated tumorigenesis. Most significantly, mechanistic investigations further unveil that circHIPK2, mediated by FUS, interacting with EIF4A3 to promote the translation of TAZ, ultimately increasing the transcription of downstream target genes CCN1 and CCN2. Taken together, circHIPK2 emerges as a key player in the shared mechanisms of IBD and CRC, modulating the Hippo signaling pathway. CircHIPK2‐EIF4A3 axis contributes to cell growth in intestinal epithelial of colitis and CRC by enhancing TAZ translation.

Abstract Pyoderma gangrenosum (PG) is a rare reactive noninfectious inflammatory dermatosis. More than 50% of PG patients have an associated systemic disease, which, in most cases, is an inflammatory bowel disease. PG affects more females than males and patients with active colitis. This case report describes a 12‐year‐old girl previously diagnosed with ulcerative colitis (UC) and on infliximab treatment. She came to our attention with a painful leg ulcer during admission for acute respiratory failure and fever. The lesion was classified as PG and a diagnosis of UC pulmonary involvement was made. Infliximab was substitute by ustekinumab and the girl is in remission after 1 year of treatment. To the best of our knowledge, this is the first case in the literature of a UC‐related paediatric PG treated with ustekinumab. Our data suggest that more studies are required as to the efficacy of ustekinumab in paediatric PG settings.

The precise etiology of inflammatory bowel diseases (IBDs) remains elusive. The Escherichia coli strain LF82 (LF82) is known to be associated with IBD, and we hypothesized that this association may be related to the chuT and shuU genes. Here we constructed a germ‐free (GF) honeybee model to investigate the effects of LF82 chuT and shuU genes on the honeybee intestine and their mechanisms. The chuT and shuU gene deletion strains LF82∆chuT and LF82∆shuU were generated by CRISPR‐Cas9. These strains, together with nonpathogenic E. coli MG1655 (MG1655) and wildtype LF82, were allowed to colonize the guts of GF honeybees to establish single bacterial colonization models. Intestinal permeability was assessed following the administration of a sterile Brilliant Blue (FCF) solution. Comprehensive transcriptomic and metabolomic analyses of intestinal samples indicated that MG1655 had few disadvantageous effects on honeybees. Conversely, colonization with LF82 and its gene‐deletion mutants provoked pronounced activation of genes associated with innate immune pathways, stimulated defensive responses, and induced expression of genes associated with inflammation, oxidative stress, and glycosaminoglycan degradation. Crucially, the LF82∆chuT and LF82∆shuU strains perturbed host heme and iron regulation, as well as tryptophan metabolism. These findings suggest that the deletion of chuT and shuU genes in E. coli LF82 may alleviate intestinal inflammation by partially modulating tryptophan catabolism. Our study proposes that targeting iron uptake mechanisms could be a potential strategy to mitigate the virulence of IBD‐associated bacteria.

Abstract Inflammatory bowel disease (IBD) is a chronic and incurable disorder associated with higher cancer risk and currently faces unsatisfactory treatment outcomes. Ferroptotic cells secrete damage‐associated molecular patterns (DAMPs) that recruit and activate immune cells, particularly macrophages. Magnolin has excellent antioxidant and anti‐inflammatory properties, but its effect on IBD has not yet been clearly understood. This study aimed to investigate the therapeutic effects and mechanism of magnolin in IBD. For this purpose, in vivo and in vitro colitis models were established using dextran sulfate sodium (DSS), followed by optimization of magnolin concentration 2.5 μg/mL in vitro and 5 mg/kg in vivo. Bioinformatics analysis identified potential magnolin target sites and evaluated ferroptosis‐associated gene expressions. Body weight, food intake, disease activity index (DAI), pathological changes, and inflammation levels were assessed. The effect of magnolin on ferroptosis and macrophages was evaluated using quantitative real time‐polymerase chain reaction (qRT‐PCR), immunofluorescent staining, flow cytometry, enzyme‐linked immunosorbent assay (ELISA), and western blotting. Results indicated that magnolin at a lower dose (5 mg/kg) alleviated DSS‐induced colitis symptoms and reduced inflammation in mice. The bioinformatics analysis showed arachidonate 5‐lipoxygenase (ALOX5) as a potential magnolin target. Furthermore, magnolin inhibited the expression of ALOX5 with no effect on GPX4. Moreover, magnolin regulated macrophage differentiation into the M2 phenotype and suppressed pro‐inflammatory factors, that is, interleukin‐6 and tumor necrosis factor‐α (IL‐6 and TNFα). These results suggested that magnolin possesses significant therapeutic potential in treating IBD by suppressing ALOX5‐mediated ferroptosis, inhibiting M1 while promoting M2 macrophages, which is envisaged to provide novel strategies for treating IBD.

Abstract Inflammatory bowel disease (IBD) is a prevalent chronic relapsing‐remitting disease that affects the digestive tract and reduces patients’ quality of life. Food bioactive compounds are a promising approach for nutritional intervention of IBD with minimal side effects. To evaluate their potential, researchers have developed various animal models that simulate human IBD, including chemically induced, spontaneous, genetically engineered, and adoptive transfer models. In this work, the main animal models, pathogenesis, symptoms, strengths, and limitations of IBD were discussed. Although these models could not perfectly replicate human IBD, they provided useful tools to study the disease's progression and therapeutic processes. In addition, taking these IBD animals as models, the specific experimental methods, intervention results, and mechanisms of food bioactive compounds to prevent or treat IBD were described in detail. The continuous improvement of animal models is crucial to gain a better understanding of IBD's etiology and pathogenesis and to evaluate the efficacy of food bioactive compounds for the effective control of IBD.

Abstract Aim To investigate whether resilience mediates the connection between caregiver burden and hope among caregivers of patients with inflammatory bowel disease (IBD). Design A cross‐sectional study. Methods Two hundred patients with IBD were conveniently sampled from two tertiary hospitals in Jiangsu Province, China. The main instruments involved the Zarit Burden Interview, the 10‐item Connor‐Davidson resilience scale, and the Herth Hope Index. We conducted descriptive analysis and Pearson correlations using SPSS 25.0. The PROCESS v3.3 macro analysed the mediating effect. We report the results in line with the STROBE checklist. Results Caregiver burden was significantly negatively connected with hope and resilience, whereas resilience positively correlated with hope. The mediation role of resilience was significant in the relationship between caregiver burden and hope, with mediating effects accounting for 47.86% of the overall effect. Conclusions Resilience partially mediates the association between caregiver burden and hope among patients with IBD. This finding highlights the protective role of resilience in undermining caregiver burden and strengthening hope. Implications for Practice In clinical practice, healthcare providers should perform routine psychological assessments for caregivers of patients with IBD. Furthermore, resilience training should be incorporated into interventions to alleviate caregiver burden and enhance hope. Patient or Public Contribution None.

Abstract Background and Aim Quality of life is reduced in people with inflammatory bowel disease (IBD) and poor sleep is prevalent in people with IBD. This study aimed to investigate the influence of sleep on quality of life (QoL) in people with inflammatory bowel disease. Methods An online questionnaire was administered through three tertiary IBD centers, social media, and through Crohn's Colitis Australia. The questionnaire included the EQ‐5D‐5L measures of health‐related QoL, the Insomnia Severity Index, the Pittsburgh Sleep Quality Index (PSQI), and validated IBD activity and mental health scores. Results There were 553 responses included with a diagnosis of Crohn's disease (62.2%), with over half on biologic therapy (53.1%). Poor sleep and clinically significant insomnia were associated with lower QoL (EQ‐5D‐5L scores: EQVAS, utility score, P

Abstract Background Helicobacter pylori (H. pylori) infection is prevalent and associated with the development of various gastric diseases. On the other hand, inflammatory bowel disease (IBD) is an immune‐related intestinal disorder influenced by factors like gut microbiota imbalance, genetic predisposition, and environmental influences. Despite extensive research on the H. pylori–IBD relationship, a comprehensive bibliometric analysis in this area is lacking. Therefore, this study aims to use bibliometric methods to explore research trends, hotspots, and frontiers in H. pylori and IBD‐related research, offering valuable insights for future research and clinical practice. Methods We retrieved relevant literature on H. pylori and IBD from the Web of Science Core Collection (WoSCC) and Scopus databases covering 2007 to 2024. We perform a comprehensive analysis within the WoSCC literature. We compare these findings with relevant results from Scopus. Results Research on H. pylori and IBD has remained prominent in recent years. The United States leads in output, with strong contributions from authors, institutions, and journals. China, despite being a developing country, shows rapid article growth, signaling growing research potential. Key topics include Crohn's disease, gut microbiota, H. pylori infection, and ulcerative colitis. Newer interests include health, cancer prevention, and chronic gastritis. Conclusion Over the past, research on H. pylori and IBD has primarily centered around epidemiology and clinical studies. The question of whether H. pylori definitively offers protective effects against IBD remains unresolved. Therefore, further investigation could explore the underlying mechanisms of their relationship or initiate long‐term prospective cohort studies to gather more compelling evidence.

Abstract Introduction Crohn's disease (CD) is a chronic, progressive inflammatory bowel disorder characterized by persistent inflammation and noncontiguous “skip lesions” throughout the gastrointestinal tract. With a prevalence of 100–300 cases per 100,000 individuals, CD is most common in Western Europe and North America. Symptoms include abdominal pain, diarrhea, fever, weight loss, and anemia, with severe cases leading to complications such as perianal abscesses and cutaneous fistulas. Treatment involves pharmaceutical interventions, bowel rest, and sometimes surgery, with biological therapies like ustekinumab and mirikizumab gaining prominence. Clinical Trials The VIVID‐1 trial assessed mirikizumab in patients with moderately to severely active CD. By Week 12, mirikizumab significantly outperformed placebo in clinical response (45.4% vs. 19.6%, p

Abstract Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent gastrointestinal inflammation, lacking a precise aetiology and definitive cure. The gut microbiome is vital in preventing and treating IBD due to its various physiological functions. In the interplay between the gut microbiome and human health, extracellular vesicles secreted by gut bacteria (BEVs) are key mediators. Herein, we explore the role of Roseburia intestinalis (R)‐derived EVs (R‐EVs) as potent anti‐inflammatory mediators in treating dextran sulfate sodium‐induced colitis. R was selected as an optimal BEV producer for IBD treatment through ANCOM analysis. R‐EVs with a 76 nm diameter were isolated from R using a tangential flow filtration system. Orally administered R‐EVs effectively accumulated in inflamed colonic tissues and increased the abundance of Bifidobacterium on microbial changes, inhibiting colonic inflammation and prompting intestinal recovery. Due to the presence of Ile‐Pro‐Ile in the vesicular structure, R‐EVs reduced the DPP4 activity in inflamed colonic tissue and increased the active GLP‐1, thereby downregulating the NFκB and STAT3 via the PI3K pathway. Our results shed light on the impact of BEVs on intestinal recovery and gut microbiome alteration in treating IBD.

Abstract Patients with glycogen storage disease type Ib (GSD‐Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD‐Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo‐polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single‐cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper‐activation of the CCL4L2‐VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD‐Ib. Collectively, the microbiota‐driven pathomechanism of IBD is demonstrated in GSD‐Ib and revealed the active role of the CCL4L2‐VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2‐VISR axis may represent a potential therapy for GSD‐associated IBD.

Abstract Background Toll‐like receptors (TLRs) are a family of fundamental pattern recognition receptors in the innate immune system, constituting the first line of defense against endogenous and exogenous antigens. The gut microbiota, a collection of commensal microorganisms in the intestine, is a major source of exogenous antigens. The components and metabolites of the gut microbiota interact with specific TLRs to contribute to whole‐body immune and metabolic homeostasis. Objective This review aims to summarize the interaction between the gut microbiota and TLR signaling pathways and to enumerate the role of microbiota dysbiosis‐induced TLR signaling pathways in obesity, inflammatory bowel disease (IBD), and colorectal cancer (CRC). Results Through the recognition of TLRs, the microbiota facilitates the development of both the innate and adaptive immune systems, while the immune system monitors dynamic changes in the commensal bacteria to maintain the balance of the host‐microorganism symbiosis. Dysbiosis of the gut microbiota can induce a cascade of inflammatory and metabolic responses mediated by TLR signaling pathways, potentially resulting in various metabolic and inflammatory diseases. Conclusion Understanding the crosstalk between TLRs and the gut microbiota contributes to potential therapeutic applications in related diseases, offering new avenues for treatment strategies in conditions like obesity, IBD, and CRC.

Abstract Until recently, diet as a therapeutic tool to treat inflammatory bowel disease (IBD) has not been proven effective. Nearly a century in the making we are in the grips of a revolution in diet therapies for IBD, driven by emerging data revealing diet as a key environmental factor associated with IBD susceptibility, and observational studies suggesting that dietary intake may play a role in the disease course of established IBD. This review summarizes the current evidence for diets trialed as induction and maintenance therapy for IBD. For Crohn's disease, exclusive enteral nutrition and the Crohn's disease exclusion diet with partial enteral nutrition are supported by emerging high‐quality evidence as induction therapy, but are short‐term approaches that are not feasible for prolonged use. Data on diet as maintenance therapy for Crohn's disease are conflicting, with some studies supporting fortification, and others suppression, of certain food components. For ulcerative colitis, data are not as robust for diet as induction and maintenance therapy; however, consistent themes are emerging, suggesting benefits for diets that are plant‐based, high in fiber and low in animal protein. Further studies for both Crohn's disease and ulcerative colitis are eagerly awaited, which will allow specific recommendations to be made. Until this time, recommendations default to population based healthy eating guidelines.

Key Clinical Message Inflammatory bowel disease is rare in infants and it includes perianal Crohn's disease, which is inflammation at or near the anus. An early diagnosis is essential to prevent the complications that may affect the development and growth of the child.

Key Clinical Message Chronic active Epstein‐Barr virus (EBV) infection‐associated enteritis (CAEAE) in nonimmunodeficient individuals is rare. To report a case of CAEAE, relevant articles were searched through databases. The clinical manifestations, endoscopic findings, strategies of treatment, prognoses, and follow‐up results of CAEAE patients were analyzed. Including this report, seven citations in the literature provide descriptions of 27 cases of CAEAE. There were 21 males and six females, with a mean age of 40 years. The main clinical manifestations were fever (25/27), abdominal pain (14/27), diarrhea (16/27), hematochezia or bloody stools (13/27), and decreased hemoglobin and red blood cell counts in routine blood tests (14/27). Elevations in inflammatory markers, white blood cell (WBC) counts, and C‐reactive protein (CRP) were common. Coagulation was often abnormal. Histopathology confirmed EBV‐encoded small nuclear RNA (EBER) in the affected tissue via in situ hybridization. The average serum EBV DNA load was 6.3 × 10^5 copies/mL. All patients had varying degrees of intestinal ulcers endoscopically, and the ulcers and pathology were uncharacterized and misdiagnosed mostly as inflammatory bowel disease (IBD). The course of the disease was progressive and later complicated by intestinal bleeding, intestinal perforation, septic shock, and a high rate of emergency surgery. However, the conditions of the patients often did not improve after surgery, and some patients soon died due to reperforation or massive hematochezia. Hormone and antiviral treatment had no obvious effect. There was a significant difference in surgical and nonsurgical survival (p

Abstract This study aimed to investigate the expression levels of tissue and serum miR‐149‐3p and miR‐149‐5p in hospitalized patients with inflammatory bowel disease (IBD). A total of 35 ulcerative colitis (UC) patients, 12 Crohn's disease (CD) patients, and 25 healthy controls were included in the study. The miRNAs expressions were measured in tissue and serum samples using quantitative real‐time polymerase chain reaction (qRT‐PCR). Inflammatory biomarkers were measured, including serum albumin, erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), tumor necrosis factor‐α (TNF‐α), and interleukin‐6 (IL‐6), and fecal calprotectin. MiR‐149‐3p and miR‐149‐5p were significantly decreased in the inflamed areas of both CD and UC patients compared to tissue controls, which was consistent with decreased serum levels in IBD patients compared to healthy controls. When distinguishing UC patients from healthy controls, serum miR‐149‐3p showed 74% sensitivity and 96% specificity, while serum miR‐149‐5p exhibited 63% sensitivity and 96% specificity. In the CD versus healthy control comparison, miR‐149‐3p achieved 100% sensitivity and 96% specificity, while miR‐149‐5p demonstrated 92% sensitivity and 96% specificity. In the UC versus CD comparison, miR‐149‐5p showed 75% sensitivity and 77% specificity, while miR‐149‐3p displayed 67% sensitivity and 80% specificity. Significant correlations were identified between the tissue and serum expression of miR‐149‐3p/5p and disease activity scores, as well as inflammatory biomarkers in both CD and UC patients. Decreased expression of miR‐149‐3p and miR‐149‐5p is associated with disease activity in IBD patients. These miRNAs demonstrate diagnostic potential and may serve as biomarkers for monitoring disease activity in IBD.

Abstract Background and Aim A reliable serum biomarker for inflammatory bowel disease (IBD) activity is needed. Vitamin D is involved in inflammation and has been demonstrated to be low in IBD patients with active disease. It is routinely measured in IBD patients. Therefore, vitamin D may have a role as a serum biomarker in IBD. This study aims to investigate whether serum vitamin D may be useful as a biomarker in IBD in a real‐world IBD population. Methods Patients were identified by review of fecal calprotectin (FCP) results, and those who had a clinical review, vitamin D test, and FCP performed within 3 months were included. Clinical scores were calculated from chart review. Nonparametric tests were used to investigate vitamin D and FCP levels, serum biomarkers, and clinical scores. Results Of 616 patients identified, 325 episodes of matched vitamin D level and biomarker data were obtained. A statistically significant correlation was found between vitamin D levels and FCP levels for all patients (r = −0.19 [s –0.29 to −0.080], P

Abstract Background Malnutrition and subsequent alterations in body composition (BC), particularly sarcopenia, are common but not yet elucidated in patients with inflammatory bowel disease (IBD); we aimed to detail the changes in BC and the characteristics of co‐occurrence of malnutrition and sarcopenia in IBD patients and to investigate its effect on quality of life. Methods This study was a multicentre, prospective, observational study involving four tertiary referral hospitals in China. The following data were collected from consecutive IBD inpatients: demographic information, medical history, recent weight change, handgrip strength (HGS) and BC parameters by bioelectrical impedance analysis (BIA). Nutritional assessments were performed through stepwise screening (Nutritional Risk Screening 2002) and diagnosis (World Health Organization‐related body mass index [BMI], subjective global assessment, European Society for Clinical Nutrition and Metabolism 2015 and Global Leadership Initiative on Malnutrition [GLIM] criteria). The quality of life was assessed by the Inflammatory Bowel Disease Questionnaire. IBD patients were compared with 1:1 sex‐, age‐ and BMI‐matched healthy controls (MHC). Results A total of 238 IBD patients (177 Crohn's disease [CD] and 61 ulcerative colitis [UC]), 68.5% male, with a mean age of 38.5 ± 14.0 years and a mean BMI of 19.8 ± 3.5 kg/m2, were recruited. Compared with MHC (n = 122), IBD patients showed significant deterioration in BC and physical function, characterized by muscle depletion (appendicular skeletal muscle mass index [ASMI], 8.0 ± 1.3 vs. 6.7 ± 1.2 kg/m2, Δ% −15.0% [−22.0%, −10.0%], P

Abstract Disrupted gastrointestinal (GI) motility is highly prevalent in patients with inflammatory bowel disease (IBD), but its potential causative role remains unknown. Herein, the role and the mechanism of impaired GI motility in colitis pathogenesis are investigated. Increased colonic mucosal inflammation is found in patients with chronic constipation (CC). Mice with GI dysmotility induced by genetic mutation or chemical insult exhibit increased susceptibility to colitis, dependent on the gut microbiota. GI dysmotility markedly decreases the abundance of Lactobacillus animlalis and increases the abundance of Akkermansia muciniphila. The reduction in L. animlalis, leads to the accumulation of linoleic acid due to compromised conversion to conjugated linoleic acid. The accumulation of linoleic acid inhibits Treg cell differentiation and increases colitis susceptibility via inducing macrophage infiltration and proinflammatory cytokine expression in macrophage. Lactobacillus and A. muciniphila abnormalities are also observed in CC and IBD patients, and mice receiving fecal microbiota from CC patients displayed an increased susceptibility to colitis. These findings suggest that GI dysmotility predisposes host to colitis development by modulating the composition of microbiota and facilitating linoleic acid accumulation. Targeted modulation of microbiota and linoleic acid metabolism may be promising to protect patients with motility disorder from intestinal inflammation.

Abstract Aim To explore factors promoting and hindering resilience in youth with inflammatory bowel disease (IBD) based on Kumpfer's resilience framework. Design A descriptive qualitative study design with an interpretative approach was used. Methods Participants consisted of 10 youths with IBD from a tertiary hospital in Beijing (China) recruited using the purposive sampling method. Data were collected by semi‐structured interviews from December 2020 to March 2021. The directed content analysis was performed for data analysis. Results Both promoting factors and hindering factors could be divided into personal factors and environmental factors. Thirteen themes were identified. The promoting factors included acceptance of illness, strict self‐management, previous treatment experience, life goals, family support, medical support and peer encouragement. Stigma, lack of communication, negative cognition, societal incomprehension, economic pressure and academic and employment pressure were hindering factors. Conclusion Health care professionals need to develop greater awareness of factors, stemming from both the individual and the outside world, that hinder or promote resilience in order to aid young patients with IBD. Building targeted nursing measures to excavate the internal positive quality of patients, provide external support and promote the development of resilience.

Abstract Introduction Involving people with lived experience is fundamental to healthcare development and delivery. This is especially true for inflammatory bowel disease (IBD) services, where holistic and personalised models of care are becoming increasingly important. There is, however, a significant lack of representation of underserved and diverse groups in IBD research, and there are significant barriers to healthcare access and utilisation among minority groups in IBD. IBD centres need to be aware of these experiences to address barriers via service changes, improve interactions with local communities and promote meaningful engagement for improved health outcomes. Methods A pragmatic community‐based approach was taken to engage with leaders and members of underserved groups across 11 workshops representing Roma, Afro‐Caribbean, people of African descent and the wider black, Asian and minority ethnic (BAME) communities, Muslim women, refugee community members, deprived areas of South Yorkshire, LGBTQ+ and deaf populations. Thematic analysis of field notes identified patterns of attention across the community groups and where improvements to services were most frequently suggested. Results Findings demonstrated several barriers experienced to healthcare access and utilisation, including language accessibility, staff attitudes and awareness, mental health and stigma, continuity of support, and practical factors such as ease of service use and safe spaces. These barriers acted as a lever to co‐producing service changes that are responsive to the health and social care needs of these groups. Conclusions Engaging with people from a range of communities is imperative for ensuring that service improvements in IBD are accessible and representative of individual needs and values. Patient or Public Contribution Local community leaders and members of community groups actively participated in the co‐design and development of improvements to the IBD service for a local hospital. Their contributions further informed a pilot process for quality improvement programmes in IBD centres.

Abstract Introduction The aim of this study was to gain consensus among young people with a stoma due to inflammatory bowel disease (IBD) on the priorities for the content of an intervention for the self‐management of stoma‐related distress. The current identification and management of distress in young people with a stoma is often suboptimal in clinical settings and there is a need for improved support resources. Methods Two consensus group meetings were carried out via online video conferencing, using nominal group technique. Participants generated, rated on a Likert scale and discussed, topics for inclusion in a future self‐management intervention. Results Nineteen young people, aged 19–33, with a stoma due to IBD took part in one of two group meetings. Participants were located across England, Scotland, and Northern Ireland. Twenty‐nine topics were generated by participants, seven of which reached consensus of ≥80%, that is, a mean of ≥5.6 on a 7‐point Likert scale. These were: receiving advice from young people with lived experience of stoma surgery; advice on/addressing concerns about romantic relationships, sex and intimacy; information about fertility and pregnancy related to stoma surgery; stoma ‘hacks’, for example, useful everyday tips regarding clothing, making bag changes easier and so forth; reflecting on and recognising own emotional response to surgery; tips on managing the stoma during the night; and processing trauma related to the illness and surgery journey. Conclusions Findings extend previous research on young people's experiences of stoma surgery, by generating consensus on young people's priorities for managing distress related to surgery and living with a stoma. These priorities include topics not previously reported in the literature, including the need for information about fertility and pregnancy. Findings will inform the development of a self‐management resource for young people with an IBD stoma and have relevance for the clinical management of stoma‐related distress in this population. Patient or Public Contribution Three patient contributors are co‐authors on this paper, having contributed to the study design, interpretation of results and writing of the manuscript. The study's Patient and Public Involvement and Engagement advisory group also had an integral role in the study. They met with the research team for four 2‐h virtual meetings, giving input on the aims and purpose of the study, recruitment methods, and interpretation of findings. The group also advised on the age range for participants. The views of young people with a stoma are the central component of the study reported in this paper, which aims to gain consensus among young people with an IBD stoma on their priorities for the content of a resource to self‐manage distress related to stoma surgery.

Abstract Background and Aim C‐reactive protein (CRP)‐to‐albumin ratio (CAR) is a novel score with prognostic value in inflammatory conditions. This study assessed the performance of CAR as an objective marker of disease activity and prediction of subtherapeutic infliximab trough levels in patients with inflammatory bowel disease (IBD). Methods A retrospective study was conducted on three different patient cohorts with IBD: patients who had (i) fecal calprotectin (FC) measurements; (ii) Mayo Endoscopic Scores; and (iii) infliximab trough levels available. The relative performances of CAR, albumin, and CRP were compared in predicting disease activity (based on FC or Mayo Endoscopic Score) and infliximab trough levels. Results In both the FC (n = 289) and endoscopy (n = 65) cohorts, albumin and CAR correlated with objective disease activity. CAR (area under the curve [AUC] 0.70) was only marginally better at detecting active disease, measured by FC, compared to CRP (AUC 0.68). A CAR >0.15 was able to detect Mayo 3 disease (AUC 0.83, sensitivity 81%, specificity 89%). Albumin (r = 0.38) and CAR (r = −0.42) correlated with infliximab trough levels (n = 204). The optimal CAR for detecting subtherapeutic infliximab trough levels was >0.08 (AUC 0.70, sensitivity 66%, specificity 64%). Both albumin and CAR were independent predictors of subtherapeutic infliximab trough levels but correlated poorly with infliximab trough levels longitudinally in the same patient. Conclusion CAR was only a modest discriminator of subtherapeutic infliximab levels and offers little more than CRP in detecting active disease. CAR has potential to detect severe Mayo 3 disease and could be calculated in patients admitted with suspected acute severe ulcerative colitis.

Abstract Background and Aim Etrolizumab is a gut‐targeted anti‐β7 integrin monoclonal antibody. However, the evidence of etrolizumab efficacy and safety in ulcerative colitis remains inconclusive. Therefore, we aim to evaluate the safety and efficacy of etrolizumab as an induction and maintenance therapy for active moderate to severe ulcerative colitis. Methods We synthesized randomized controlled studies (RCTs) from MEDLINE, Scopus, EMBASE, PubMed, Web of Science, and Cochrane Library until April 2023. The risk ratio (RR) for dichotomous outcomes with the corresponding 95% confidence interval (CI) was used. The study protocol was registered in PROSPERO with ID: CRD42023437040. Results Five RCTs with 1849 participants were included. The etrolizumab group had a significant clinical response (RR: 1.28 with 95% CI [1.08, 1.51], P = 0.005), clinical remission rates during the induction phase (RR: 2.47 with 95% CI [1.48, 4.11], P = 0.0005), compared with the placebo group in ulcerative colitis; however, there was no statistically significant difference between the two groups, regarding the corticosteroids‐free remission rate (RR: 1.92 with 95% CI [0.94, 3.92], P = 0.07). Moreover, endoscopic improvement, endoscopic remission, and histologic remission rates were observed more in the etrolizumab group during both the induction and maintenance phases. For safety outcomes, etrolizumab was significantly safer, but any adverse event was higher in the etrolizumab group than in the placebo. Conclusion Etrolizumab shows its effectiveness as both an induction and maintenance therapy for moderate or severe UC. The findings demonstrate its positive impact on clinical, endoscopic, and histologic remission rates. Regarding safety, other than any side effects, etrolizumab showed a good safety than a placebo.

Abstract Inflammatory bowel disease (IBD) is a significant global health concern. The gut microbiota plays an essential role in the onset and development of IBD. Sanghuangporus (SH), a traditional Chinese medicinal mushroom, has excellent anti‐inflammatory effects and is effective at modulating the gut microbiota. Despite these attributes, the specific anticolitic effects of SH and the mechanisms through which the gut microbiota mediates its benefits remain unclear. Herein, we demonstrated that polyphenol‐rich extract from SH effectively alleviated the pathological symptoms of dextran sodium sulfate (DSS)‐induced colitis in mice by modulating the gut microbiota. Treatment with SH distinctly enriched Alistipes, especially Alistipes onderdonkii, and its metabolite 5‐hydroxyindole‐3‐acetic acid (5HIAA). Oral gavage of live A. onderdonkii or 5HIAA potently mitigated DSS‐induced colitis in mice. Moreover, both 5HIAA and SH significantly activated the aromatic hydrocarbon receptor (AhR), and the administration of an AhR antagonist abrogated their protective effects against colitis. These results underscore the potent efficacy of SH in diminishing DSS‐induced colitis through the promotion of A. onderdonkii and 5HIAA, ultimately activating AhR signaling. This study unveils potential avenues for developing therapeutic strategies for colitis based on the interplay between SH and the gut microbiota.

Abstract Structural repair of the intestinal epithelium is strongly correlated with disease remission in inflammatory bowel disease (IBD); however, ulcer healing is not addressed by existing therapies. To address this need, this study reports the use of a small molecule prolyl hydroxylase (PHD) inhibitor (DPCA) to upregulate hypoxia‐inducible factor one‐alpha (HIF‐1α) and induce mammalian regeneration. Sustained delivery of DPCA is achieved through subcutaneous injections of a supramolecular hydrogel, formed through the self‐assembly of PEG‐DPCA conjugates. Pre‐treatment of mice with PEG‐DPCA is shown to protect mice from epithelial erosion and symptoms of dextran sodium sulfate (DSS)‐induced colitis. Surprisingly, a single subcutaneous dose of PEG‐DPCA, administered after disease onset, leads to accelerated weight gain and complete restoration of healthy tissue architecture in colitic mice. Rapid DPCA‐induced restoration of the intestinal barrier is likely orchestrated by increased expression of HIF‐1α and associated targets leading to an epithelial‐to‐mesenchymal transition. Further investigation of DPCA as a potential adjunctive or stand‐alone restorative treatment to combat active IBD is warranted.

Abstract Background Inflammatory bowel diseases (IBDs) pose significant challenges in terms of treatment non‐response, necessitating the development of novel therapeutic approaches. Although biological medicines that target TNF‐α (tumour necrosis factor‐α) have shown clinical success in some IBD patients, a substantial proportion still fails to respond. Methods We designed bispecific nanobodies (BsNbs) with the ability to simultaneously target human macrophage‐expressed membrane TNF‐α (hmTNF‐α) and IL‐23. Additionally, we fused the constant region of human IgG1 Fc (hIgG1 Fc) to BsNb to create BsNb‐Fc. Our study encompassed in vitro and in vivo characterization of BsNb and BsNb‐Fc. Results BsNb‐Fc exhibited an improved serum half‐life, targeting capability and effector function than BsNb. It's demonstrated that BsNb‐Fc exhibited superior anti‐inflammatory effects compared to the anti‐TNF‐α mAb (infliximab, IFX) combined with anti‐IL‐12/IL‐23p40 mAb (ustekinumab, UST) by Transwell co‐culture assays. Notably, in murine models of acute colitis brought on by 2,4,6‐trinitrobenzene sulfonic acid（TNBS) and dextran sulphate sodium (DSS), BsNb‐Fc effectively alleviated colitis severity. Additionally, BsNb‐Fc outperformed the IFX&UST combination in TNBS‐induced colitis, significantly reducing colon inflammation in mice with colitis produced by TNBS and DSS. Conclusion These findings highlight an enhanced efficacy and improved biostability of BsNb‐Fc, suggesting its potential as a promising therapeutic option for IBD patients with insufficient response to TNF‐α inhibition. Key points A bispecific nanobody (BsNb) was created to target TNF‐α and IL‐23p19, exhibiting high affinity and remarkable stability. BsNb‐Fc inhibited the release of cytokines in CD4+T cells during co‐culture experiments. BsNb‐Fc effectively alleviated colitis severity in mouse model with acute colitis induced by DSS or TNBS, outperforming the IFX&UST combination.

Abstract Most patients with inflammatory bowel disease (IBD) develop anemia, which is attributed to the dysregulation of iron metabolism. Reciprocally, impaired iron homeostasis also aggravates inflammation. How this iron‐mediated, pathogenic anemia‐inflammation crosstalk is regulated in the gut remains elusive. Herein, it is for the first time revealed that anemic IBD patients exhibit impaired production of short‐chain fatty acids (SCFAs), particularly butyrate. Butyrate supplementation restores iron metabolism in multiple anemia models. Mechanistically, butyrate upregulates ferroportin (FPN) expression in macrophages by reducing the enrichment of histone deacetylase (HDAC) at the Slc40a1 promoter, thereby facilitating iron export. By preventing iron sequestration, butyrate not only mitigates colitis‐induced anemia but also reduces TNF‐α production in macrophages. Consistently, macrophage‐conditional FPN knockout mice exhibit more severe anemia and inflammation. Finally, it is revealed that macrophage iron overload impairs the therapeutic effectiveness of anti‐TNF‐α antibodies in colitis, which can be reversed by butyrate supplementation. Hence, this study uncovers the pivotal role of butyrate in preventing the pathogenic circuit between anemia and inflammation.

Key Clinical Message The rare co‐occurrence of takayasu arteritis (TAK) and ulcerative colitis (UC), presenting with asymptomatic onset and neurological complications, highlights the importance of an integrated diagnostic approach for overlapping autoimmune conditions. Abstract We present a rare case of a 44‐year‐old female diagnosed with both UC and TAK, characterized by an unusual acute asymptomatic onset accompanied by neurological manifestations. The patient exhibited symptoms of acute ischemic stroke along with vascular abnormalities, as well as colon inflammation associated with UC. The patient's asymptomatic presentation at the onset differs from previously reported cases. The presence of additional complications, such as hepatocellular adenoma and primary sclerosing cholangitis, further complicated the diagnostic challenges. The patient's treatment involved a combination of methylprednisolone, azathioprine, and prednisolone leading to improved clinical outcomes. This case emphasizes the complexity involved in diagnosing overlapping conditions and highlights the significance of TAK in presenting atypical manifestations in relation to UC. Furthermore, this case contributes to the limited literature, underscoring the need for early detection and comprehensive treatment approaches.

Abstract Inflammatory bowel disease (IBD), a common chronic gastrointestinal disease in humans, has emerged as a global public health challenge. Dihydromyricetin (DHM) has anti‐inflammatory and antioxidant activities, which can alleviate inflammation. In this study, we explored the effect and underlying mechanism of DHM on dextran sulfate sodium (DSS)‐induced colitis in mice and porcine jejunum epithelial cells (IPEC‐J2) exposed to lipopolysaccharide (LPS). We found that DHM alleviated loss of weight, diarrhea, and damage of colon structure in colitis mice. For the intestinal microbial, a significant rise in the amount of the potentially beneficial genera and a decline in the amount of harmful genera were observed in DHM‐treated colitis mice. Metabolomic analysis of cecal content revealed that DHM restored phenylalanine metabolism, arginine biosynthesis, and arachidonic acid metabolism disorders caused by intestinal inflammation. Moreover, DHM decreased the level of pro‐inflammatory cytokines and reactive oxygen species in LPS‐treated IPEC‐J2 cells. DHM also reduced the expression of MyD88 and nuclear factor‐κB (NF‐κB). In summary, we found that 125 mg/kg DHM administration alleviated diarrhea, reinstated intestinal barrier function, modulated intestinal dysbiosis, and suppressed the expression of myeloid differentiation factor 88 (MyD88) and NF‐κB. Therefore, DHM may be a potentially therapeutic agent for IBD.

Abstract Background The role of diet in the pathogenesis and treatment of chronic enteropathies (CE) in dogs is unresolved. Objectives To compare the ability of diets composed of hydrolyzed fish, rice starch, and fish oil without (HF) or with prebiotics, turmeric, and high cobalamin (HF+) against a limited ingredient diet containing mixed nonhydrolyzed antigens and oils (control) to resolve clinical signs and maintain serum cobalamin and folate concentrations in dogs with nonprotein losing CE (non‐PLE). To determine the ability of hydrolyzed fish diets to support recovery and remission in dogs with PLE. Animals Thirty‐one client‐owned dogs with CE: 23 non‐PLE, 8 PLE. Methods Randomized, blinded, controlled trial. Diets were fed for 2 weeks; responders continued for 12 weeks. Nonresponders were crossed over to another diet for 12 weeks. Response was determined by standardized clinical evaluation with long‐term follow‐up at 26 weeks. Concurrent medications were allowed in PLE. Results Nineteen of 23 (83%; 95% confidence interval [CI], 60%‐94%) non‐PLE CE responded clinically to their initial diet, with no difference between diets (P > .05). Four nonresponders responded to another diet, with sustained remission of 18/18 (100%; 95%CI, 78%‐100%) at 26 weeks. Serum cobalamin concentration was increased (P

Abstract Aims To investigate the diagnostic accuracy of fecal calprotectin (FC) for inflammatory bowel disease (IBD) and organic gastrointestinal disease (OGID) in primary care. To examine the association with demographic factors, symptoms and concomitant medical therapy. Methods A retrospective analysis of data on all semiquantitative FC tests from individuals ≥18 years conducted in primary care in Östergötland County in 2010. A 5‐year follow‐up with inclusion of new gastrointestinal diagnoses. Results A total of 1293 eligible patients were included. IBD was found in 8.8% and other OGID in 30.8% of patients with positive FC. Positive FC was associated with diarrhea, age >60 years, duration 35 years, abnormal clinical findings, and duration 35 years, should encourage a prioritized investigation. Use of NSAID, PPI, and ASA may affect the diagnostic accuracy of FC for IBD and OGID.

Abstract Polysaccharides are typically resistant to digestion in the gastrointestinal tract and are instead degraded by gut microbiota in the colon. As such, they are commonly employed as carriers for colon‐targeted drugs, with the potential to regulate gut microbiota. Pectin, carrageenan, guar gum, and xanthan gum are commonly used polysaccharide carriers, but their degradation in the gut microbiota under colitis conditions as well as their effects on gut microbiota remains unclear. In this study, we performed the in vitro fermentation of these four polysaccharides using colonic content microbiota from mice with colitis and evaluated the degree of polysaccharide degradation and the effects on pH, short‐chain fatty acids, and gut microbiota. Our findings indicate that pectin and guar gum had a greater degree of degradation and promoted the production of butyrate, inhibited the proliferation of harmful bacteria (e.g., Enterobacteriaceae), and increased beneficial bacteria (e.g., Bifidobacterium). In contrast, carrageenan and xanthan gum promote the proliferation of Enterobacteriaceae. These results provide theoretical guidance for the selection of drug delivery carriers for inflammatory bowel disease treatment and provide information on the relationship between polysaccharides and gut microbiota.

Abstract Background and Aim Azathioprine (AZA) forms the cornerstone for maintenance of sustained remission in inflammatory bowel disease (IBD). There is apprehension regarding the long‐term effectiveness and safety of AZA in IBD. We present our experience with AZA use and outcomes in a cohort of IBD patients followed up over a long period of time. Methods Records of 507 IBD patients under treatment at a single, tertiary care center in south India between 2013 and 2022 were evaluated retrospectively. Long‐term compliance, tolerance, clinical outcome at the point of last follow‐up, type and duration to the onset of adverse events, and subsequent amendment to treatment with regard to AZA were analyzed. Results Of 507 patients with IBD, 320 patients (207 Crohn's disease [CD], 113 ulcerative colitis [UC]) who received AZA were included. The median follow‐up was 41 months (interquartile range 15.5–77.5). Total duration of exposure was 1359 patient‐years with median usage of 33 months. Of the patients, 26.9% received AZA for >5 years. Mean initiation and maximum doses of AZA were 0.97 and 1.72 mg/kg/day. Among the participants, 20.6% experienced side effects, including myelotoxicity (7.2%) and gastrointestinal intolerance (5.6%). Six patients developed malignancy. Among the side effects, 39.4% of side effects were dose‐dependent. Among the patients, 38.1% had relapses requiring pulse corticosteroid therapy, and 16.2% had more than one relapse after commencement of AZA. AZA was continued till the last follow‐up in 76.5%. Among the patients, 49.7% (UC 51.3, CD 48.8) attained durable remission without biologics, and 5.3% continued to have active disease. Conclusion AZA is safe and effective in the long‐term in IBD. Effectiveness, tolerance, and compliance with AZA are well sustained beyond 5 years of usage and comparable between UC and CD.

Abstract Background and Aim Arthritis is a recognized extra‐intestinal manifestation of inflammatory bowel disease (IBD). Studies show altered uric acid metabolism in IBD. This study aims to investigate the association between IBD and gout. Methods We used a multi‐center database (Explorys Inc.) consisting of data from several US healthcare systems. We identified adults diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) between 1999 and 2022. In this cohort, we identified patients diagnosed with gout. We collected demographic data and identified patients diagnosed with IBD‐associated arthritis and those who had intestinal resection. Risk factors associated with gout were collected. Multivariate analysis was used. Results Out of the 69 260 780 patients in the database, we identified 209 020 patients with UC (0.30%) of whom 9130 had gout (4.3%). Additionally, 249 480 had CD (0.36%) of whom 14 000 had gout (5.61%). Males were more prevalent in the UC and gout group than in the CD and gout group (58% vs 51%). After adjustment, CD was significantly associated with gout (odds ratio [OR] 1.68, confidence interval [CI]: 1.60–1.75). UC was also significantly associated with gout (OR 1.38, CI: 1.31–1.44). In subgroup analysis with intestinal resection, CD patients who had intestinal resection had higher association with gout versus those without surgery (OR 2.34, CI: 2.25–2.43). Similar increase was observed in the UC group with intestinal resection (OR 1.53, CI: 1.49–1.56). Conclusion IBD is strongly associated with gout, with higher correlation observed with CD. Intestinal resection is associated with an increase in the risk of gout. Patients with IBD who present with new‐onset arthritis should be investigated for gout.

Abstract Background and Aim Acute severe ulcerative colitis (ASUC) remains a significant cause of morbidity and healthcare utilization. This study aimed to characterize the total healthcare costs of ASUC, explore factors associated with significant cost over the 12 months following an index admission, and document outcomes including corticosteroid exposure. Methods Patients admitted from January 2016 until January 2021 for ASUC to a tertiary inflammatory bowel disease (IBD) center in Australia were identified via retrospective chart review. Costs were calculated over a 12‐month period following index admission. Results Seventy‐two patients (30 [42%] female, median age 39 [IQR 27–54] years) were included. The median length of stay of index admission was 6 days (IQR 5–10 days). The median cost of index admission was 7829 AUD, which was driven by the initial length of stay (P

Abstract Background Both inflammatory bowel disease (IBD) and hepato‐pancreato‐biliary cancers (HPBC) have been established to cause a huge socioeconomic burden. Epidemiological studies have revealed a close association between IBD and HPBC. Methods Herein, we utilized inverse‐variance weighting to conduct a two‐sample Mendelian randomization analysis. We sought to investigate the link between various subtypes of IBD and HPBC. To ensure the accuracy and consistency of our findings, we conducted heterogeneity tests, gene pleiotropy tests, and sensitivity analyses. Results Compared to the general population, IBD patients in Europe exhibited a 1.22‐fold increased incidence of pancreatic cancer (PC) with a 95% confidence interval (CI) of 1.0022–1.4888 (p = 0.0475). We also found a 1.14‐fold increased incidence of PC in Crohn's disease (CD) patients with (95% CI: 1.0017–1.3073, p = 0.0472). In the East Asian population, the incidence of hepatocellular carcinoma (HCC) was 1.28‐fold higher (95% CI = 1.0709–1.5244, p = 0.0065) in IBD patients than in the general population. Additionally, ulcerative colitis (UC) patients displayed 1.12‐fold (95% CI: 1.1466–1.3334, p

Key Clinical Message Brucellosis, caused by gram‐negative coccobacilli of the genus Brucella, is a zoonotic disease with bone and joint complications being common. However, acute abdomen with intestinal perforation is rare. We present a case of a 69‐year‐old man diagnosed with acute diffuse peritonitis and intestinal perforation due to Brucella infection. Surgical intervention revealed ileocecal perforation with wheel spoke‐like necrosis. The patient underwent partial resection, ileum closure, and ileostomy. Positive blood culture and Brucella agglutination confirmed the diagnosis. Targeted tetracycline and aminoglycoside treatment led to recovery.

Abstract Introduction Regulatory T cells (Tregs) play an important role in inflammatory bowel diseases (IBDs) through modulating intestinal inflammation. However, the factors affecting Treg function and plasticity during IBD progression are not thoroughly disclosed. The current study aims to reveal new molecular mechanisms affecting Treg plasticity. Methods A mouse strain, in which tdTomato and enhanced green fluorescent protein were under the control of the Foxp3 promoter and Il17a promoter, was established and subjected to colitis induction with dextran sulfate sodium. The existence of Tregs and IL‐17‐expressing Tregs (i.e., Treg/T helper 17 [Th17] cells) were observed and sorted from the spleen, mesenteric lymph nodes, and lamina propria by flow cytometry, followed by measuring Sirtuin2 (Sirt2) expression using quantitative reverse transcription polymerase chain reaction and Immunoblotting. Lentivirus‐induced Sirt2 silencing was applied to determine the impact of Sirt2 on Treg polarization to Treg/Th17 cells and even Th17 cells. The effect of Sirt2 on Stat3 was analyzed by flow cytometry and immunoblotting. Results Sirt2 was highly expressed in lamina propria Tregs and it moderately suppressed Foxp3 expression as well as the immunosuppressive function of Tregs. Surprisingly, lentivirus‐mediated Sirt2 silencing promoted the generation of Treg/Th17 cells out of Tregs. Sirt2 silencing also enhanced the generation of Th17 cells out of Tregs under the Th17 induction condition. Furthermore, Sirt2 inhibited Th17 induction by suppressing the protein level of the signal transducer and activator of transcription 3. Conclusion Sirt2 suppresses Treg function but also inhibits Treg polarization toward Treg/Th17 cells and Th17 cells. The ultimate effect of Sirt2 on colitis might depend on the balance among Tregs, Treg/Th17 cells, and Th17 cells.

Abstract Background For adults with inflammatory bowel disease (IBD), they experience many challenges in dietary decision‐making. Thus, this study examined the perspective and experiences of adults with IBD in dietary decision‐making. Objective This study aimed to explore the perception and consideration of people with IBD in their daily dietary decisions through monitoring, interpretation and action during the decision‐making process. Design A qualitative study of individuals affected by IBD was conducted through semistructured interviews. Results Twenty patients were recruited from four tertiary hospitals in Nanjing, China, and each participant completed a semistructured interview. The majority of participants reported on the process and experience of dietary decision‐making. Key themes were categorised into three stages: (1) assessing needs, preferences and food cues (monitor); (2) moving from experience to expertise (interpret) and (3) balancing expectations amidst limitations (act). The majority of participants reported that their decisions were shaped by assessing current disease status and food cues. Those interviewed with IBD were willing to make tradeoffs for bowel stability, but their decisions were also influenced by past dietary experiences and traditional Chinese beliefs. The lack of awareness of dietary guidelines was a significant barrier to healthy eating decisions. Positive or negative feelings accompanied dietary decisions. Conclusion Although most people with IBD change their diet after diagnosis, the changes made are often inconsistent with existing dietary recommendations. Several factors can influence the dietary decision‐making process. This study will help assess the experiences of people with IBD in dietary decision‐making to encourage the formation of targeted dietary health and well‐being interventions. Knowledge of nutrition and diet should be provided in education and training programmes for IBD management. Patient or Public Contribution The first three authors of this paper were the lead researchers in this study's design. These authors were mentored by patient researchers who also contributed to the manuscript, and the research process was co‐lead and directed by other patient participants and consultants. The results of this paper were directly obtained from patient participants.

Abstract Sarcopenia is a condition marked by progressive loss of skeletal muscle mass and function while frailty is a multidimensional concept characterized by diminished physiological reserve and increased vulnerability to stressors. Both of these were previously considered as related to aging and shown to impact the quality of life and carry prognostic significance. Emerging data show that both sarcopenia and frailty carry similar relevance in chronic illness. Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract and malnourishment, both of which contribute to the development of sarcopenia by increasing protein breakdown and reducing protein synthesis. The coexistence of frailty further compounds the clinical complexity of IBD patients. Published evidence suggests a bidirectional association with IBD contributing to muscle wasting, while the resultant sarcopenia and frailty could further exacerbate the disease course. Sarcopenia and frailty are independently associated with adverse outcomes, including hospitalizations, increased surgical interventions, and surgical complications. As therapeutic strategies for IBD evolve, understanding the nuanced relationship between inflammatory bowel disease, sarcopenia, and frailty is crucial for devising holistic management. Comprehensive care should encompass not only disease‐modifying therapies but also interventions targeting frailty and sarcopenia, as they have been shown to have a significant impact not only on the disease course but also on the quality of life. Future research could focus on further elucidating underlying mechanisms, simple screening strategies, and developing targeted interventions to improve the overall quality of life for individuals grappling with the complex interplay of IBD, sarcopenia, and frailty.

Abstract Inflammatory bowel disease (IBD), which encompasses ulcerative colitis (UC) and Crohn's disease (CD), refers to a chronic and recurrent nonspecific inflammatory condition affecting the mucosal and submucosal layers of the intestines. A positive family history has been identified as a risk factor for the onset of IBD, likely influenced by genetic and environmental factors. In addition to intestinal damage, patients may have extraintestinal manifestations such as inflammation of the skin, eyes, and joints, inflammation of the liver or bile ducts, kidney stones, iron‐deficiency anemia, and growth retardation in children, which may complicate diagnosis and treatment. Therefore, investigating the mechanisms of IBD and finding precise therapeutic targets provides enormous benefits to patients with IBD. Multiple studies have consistently demonstrated the influential role of dietary metabolism and aging in the development of IBD. Moreover, emerging evidence suggests that aging often coincides with alterations in epigenetic modifications, while diet metabolism mediates these epigenetic changes. Epigenetics has emerged as a prospective field for identifying novel biomarkers to facilitate the diagnosis, prognosis, and treatment of diseases. Therefore, in this perspective, we summarize the cross‐talk between epigenetic modifications, diet metabolism, and aging in the pathogenesis of IBD and attempt to identify new potential therapeutic targets and strategies.

Abstract Background Chronic enteropathy (CE) is common in dogs and can occur with multiple etiologies including food‐responsive enteropathy (FRE) and idiopathic inflammatory bowel disease (IBD). Hypothesis/Objective To study the protein profile and pathway differences among dogs with FRE, IBD, and healthy controls using serum proteome analysis. Animals Nine CE dogs with signs of gastrointestinal disease and histologically confirmed chronic inflammatory enteropathy and 16 healthy controls. Methods A cross‐sectional study with cases recruited from 2 veterinary hospitals between May 2019 and November 2020 was performed. Serum samples were analyzed using mass spectrometry‐based proteomic techniques. Results Proteomic profiles showed marked variation in relative protein abundances. Forty‐five proteins were significantly (P ≤ .01) differentially expressed among the dogs with CE and controls with ≥2‐fold change in abundance. The fold change of dogs with IBD normalized to controls was more pronounced for the majority of proteins than that seen in the dogs with FRE normalized to control dogs. Proteins involving reactive oxygen species, cytokine activation, acute phase response signaling, and lipid metabolism were altered in dogs with CE. Conclusions and Clinical Importance Cytokine alterations, acute phase response signaling, and lipid metabolism are likely involved in pathogenesis of CE. Although there are insufficient current data to justify the use of proteomic biomarkers for assessment of CE in dogs, our study identifies potential candidates.