BACKGROUND AND AIMS:Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract. While infliximab (IFX) offers significant benefits, 10%-30% of patients remain non-responders initially. This study employs artificial intelligence with multimodal integration to improve treatment response prediction and advance precision medicine. METHODS:We conducted a retrospective analysis of clinical data from patients with CD. The endpoint event was defined as primary non-response within 14 weeks of treatment. The multimodal dataset included laboratory indices, computed tomography enterography (CTE), and endoscopic histopathology based on whole-slide biopsy images. A TabNet model, originally designed for tabular data and here applied to clinical and laboratory features, was developed using a multi-instance learning framework to incorporate this multimodal information for predicting primary non-response to IFX. Finally, the multimodal model was validated in an independent external test cohort. RESULTS:The study included 188 patients, with 93 in the internal training set, 38 in the internal validation set, and 57 in the test set from an independent external cohort. The model utilizing pathological features achieved an area under the receiver operating characteristic (AUC) of 0.789 in internal validation. When combining pathological and radiological features, the AUC was 0.844. The optimal multimodal model integrating histology, radiology, and clinical features achieved an AUC of 0.852 in the internal validation set and 0.858 in the external test set. CONCLUSIONS:The study developed a multimodal deep learning model accurately predicting IFX primary non-response, offering a tool to guide individualized therapy and improve CD outcomes.

Background and aims Long-term outcomes for Crohn's disease (CD) patients treated with infliximab (IFX) remain suboptimal. We developed and validated a clinical decision support tool (CDST) to predict sustained remission in CD patients treated with infliximab (IFX). Methods This multicenter observational study analyzed 746 CD patients across three cohorts. Sustained clinical remission (CREM) was defined as steroid-free Crohn's Disease Activity Index (CDAI) <150 at week 104. Using logistic regression, predictors were weighted by inverse variance. The CDST was internally validated (Cohort I, n = 113) and externally validated (Cohort II, n = 367). Results Key predictors of CREM included: prior biologic exposure (-18 points), penetrating disease (B3 phenotype, -7 points), albumin (+0.5/gL), younger age (-0.3/year), and absence of antibody to infliximab formation (ATI, +17 points). The model demonstrated strong discrimination (AUC 0.791 [95% CI 0.708-0.875]) and calibration (Brier score: 0.191). External validation AUC was 0.611 (95% CI 0.546-0.675), indicating modest generalizability. Risk stratification via CDST categorized patients into low- (<6 points), intermediate- (6-25), and high-risk (>25) groups. A cutoff of 25 points predicted 2-year CREM with 60% (95%CI 53.2%-66.5%) sensitivity and 52% (95% CI 41.2%-1.8%) specificity. Conclusions We developed and validated a CDST to identify CD patients likely to achieve sustained remission on IFX therapy. By stratifying patients into distinct risk profiles, it guides personalized therapy initiation and monitoring.

BACKGROUND:Ulcerative colitis (UC) exhibits a heterogeneous clinical course, complicating prognostication and therapeutic decision making. Current tools inadequately predict progression or identify patients most likely to benefit from biologic therapies. We aimed to develop a machine learning model for risk stratification and evaluate its utility in optimizing biologic therapy outcomes. METHODS:In this multicenter retrospective study, we analyzed 481 UC patients as the training cohort and 131 external validation patients. Disease progression-defined as treatment escalation, UC-related hospitalization, or surgery-served as the primary endpoint. Four models (Cox regression, logistic regression, random forest, XGBoost) were developed to predict progression risk. Biologic-treated patients (n = 235) were stratified into risk groups using the optimal model, with outcomes including mucosal healing, relapse, and acute severe UC assessed. RESULTS:The random forest model demonstrated superior performance, achieving an area under the curve of 0.959 in training set and 0.759 in validation set. High-risk biologic-treated patients (n = 172) exhibited lower mucosal healing rates (33.7% vs 55.2%; P = .049) and higher hazards of clinical relapse (hazard ratio [HR], 3.35; P = .003), hospitalization (HR, 2.03; P = .014), and acute severe UC (HR, 2.70; P = .030) compared with low-risk patients (n = 63). No differences in serological remission, surgery, or biologic switching were observed. CONCLUSIONS:Our random forest model enables precise risk stratification in UC, distinguishing patients with divergent responses to biologics. Low-risk patients derive significant benefit from timely biologics, while high-risk subgroups may require intensified strategies. This framework advances personalized UC management, though prospective validation is warranted.

Background: Hereditary angioedema (HAE) is a rare, severe, disabling, and life-threatening disorder characterized by recurrent and unpredictable edema of skin and mucous membranes. Gastrointestinal edema, often presenting as abdominal pain, is common but frequently misdiagnosed, leading to unnecessary surgeries. This study aims to characterize gastrointestinal edema in HAE patients to improve early diagnosis and guide treatment. Method: We analyzed 61 patients with HAE who were admitted in our hospital between April 1, 2023 and August 31, 2025. Data on demographic characteristics, clinical manifestations, laboratory findings, imaging results, and treatment outcomes were collected through questionnaires and hospital electronic records. Result: Among the patients, 86.9% experienced gastrointestinal edema, mostly characterized by abdominal pain (94.3%), nausea (79.2%), and diarrhea (71.7%). Misdiagnosis occurred in 73.6% of cases, and 22.6% underwent unnecessary surgeries. The median age of gastrointestinal edema onset was 16.0 years, with the most severe episodes occurring at a median age of 25.0 years. The median annual frequency of attacks was 4.0/year, with a median severity score of 7.0. Acute attacks showed elevated D-dimer, white blood cells, neutrophils, and hemoglobin. CT imaging frequently revealed intestinal wall thickening and abdominal-pelvic effusion. Lanadelumab demonstrated superior efficacy over danazol in reducing both the frequency and severity of edema attacks, while icatibant significantly shortened the duration of edema episodes. Conclusion: This study updates the clinical and imaging features of gastrointestinal edema in Chinese patients with HAE, identifies biomarkers of gastrointestinal edema attacks, and highlights the efficacy of lanadelumab and icatibant, aiding timely diagnosis and treatment.

Background: Transmural healing (TH) is an emerging therapeutic target in Crohn’s disease (CD). Visceral adipose tissue (VAT) is associated with the prognosis of CD, but few studies investigate the ability of VAT in predicting TH. Objectives: We aimed to quantitatively assess VAT by magnetic resonance enterography (MRE) and evaluate the prediction of baseline VAT volume for TH in CD patients with Ustekinumab (UST) treatment. Design: This is an observational study. Methods: We retrospectively included CD patients receiving UST treatment, with bowel wall thickness (BWT) >3 mm assessed by MRE at baseline. Clinical characteristics, laboratory, endoscopic, and MRE indicators were evaluated at baseline, week 26 (W26), and week 78 (W78) of the therapy. Quantification of VAT volume was assessed by MRE at baseline, and adjusted by body mass index (BMI). The TH was defined as BWT ⩽3 mm without any signs of inflammation at W26 and W78. Results: Sixty-two patients were included in our study. After UST treatment for W26 and W78, 8 (13.1%) and 13 (21.0%) patients achieved TH. Compared with baseline, laboratory indicators such as C-reactive protein and erythrocyte sedimentation rate, simple endoscopic score for CD, and BWT were significantly improved at W26 and W78. We divided patients into the TH and non-TH groups at both W26 and W78, and found that adjusted VAT volume at baseline was significantly lower in the W26-TH and W78-TH groups. Adjusted VAT volume was then categorized into four scores by quartiles, and multivariable analysis showed that baseline VAT score could negatively predict W26-TH (odds ratio (OR) = 0.296, p = 0.018) and W78-TH (OR = 0.419, p = 0.012). Conclusion: Our study demonstrated that baseline VAT was an independent risk factor for predicting both short- and long-term TH in CD patients receiving UST. Patients with lower VAT volume at baseline were more likely to achieve TH after UST treatment.

OBJECTIVES:Vonoprazan was approved in China for reflux esophagitis (RE) in 2019; however, its real-world safety and effectiveness remain undetermined. We aimed to evaluate the safety of vonoprazan in patients and its effectiveness in patients with RE in a real-world setting. METHODS:In this prospective, non-interventional, real-world study, vonoprazan 20 mg was administered orally daily for 4 or 8 weeks. Primary endpoints were incidence rates of adverse events (AEs), serious AEs (SAEs), and adverse drug reactions (ADRs). Secondary endpoints included proportions of patients with RE without typical gastroesophageal reflux disease (GERD) symptoms (complete symptom relief) at baseline and Week 4, relief of heartburn/regurgitation symptoms (all day/nighttime) during Week 1, and mean change in GERD Questionnaire (GERDQ) score at Week 4. RESULTS:Of the 2829 patients with safety data, 488 (17.2%) reported ≥ 1 AE; 29 (1.0%) reported ≥ 1 SAE; and 129 (4.6%) reported ≥ 1 ADR. Of 1796 patients with RE and effectiveness data, the proportion without typical symptoms of GERD increased from 20.1% (95% confidence interval [CI] 18.29-22.05) at baseline to 55.2% (95% CI 52.63-57.79) at Week 4 (change: 35.1%, 95% CI 31.95-38.25). Complete relief from heartburn, nighttime heartburn, regurgitation, and nighttime regurgitation was observed in 32.3% (314/971), 43.8% (427/975), 27.0% (262/971), and 40.5% (395/976) patients, respectively, during Week 1. Mean change in GERDQ score (n = 1464) improved by Week 4 (-1.70). CONCLUSION:Vonoprazan is well tolerated through 8 weeks in patients and improves symptoms in patients with RE in the real-world setting in China (VIEW; NCT04501627).

Dedicator of cytokinesis 2 (DOCK2) is a guanine nucleotide exchange factor upregulated in patients with inflammatory bowel disease (IBD), yet its role in intestinal homeostasis remains obscure. Here, we show that both systemic and T cell–specific Dock2-deficient mice develop exacerbated chemical-induced colitis, characterized by reduced CD8⁺ T cells and impaired IFN-γ production, alongside elevated IL-22 and Reg3γ/β antimicrobial peptides (AMPs), and accompanied with decreased colonization of Akkermansia (A.) muciniphila, a beneficial Verrucomicrobia species. Reg3γ/β expression was diminished in IL-22– and RORγt–deficient mice, and both AMPs inhibited A. muciniphila growth. Co-housing with wild-type mice or A. muciniphila reconstitution rescued colitis severity in Dock2-deficient mice. Pharmacologic inhibition of Dock2-Rac1 signaling suppressed IFN-γ in murine and human T cells. Mechanistically, IFN-γ restricted IL-22 by enhancing H3K27 trimethylation on Ahr promoter and suppressing AHR transcription. These findings identify a Dock2–IFN-γ–IL-22–Reg3 axis that controls commensal microbiota and colitis. Targeting Dock2 signaling may offer new therapeutic opportunities in IBD.

Background Intestinal fibrosis, a hallmark complication of Crohn's disease (CD), frequently progresses to stricture formation and surgical intervention. Fibroblast metabolic reprogramming is important in organ fibrosis. However, its role in intestinal fibrogenesis of CD remains elusive. Objective We aim to explore the metabolic reprogramming of fibroblasts and its upstream regulators during intestinal fibrosis of CD. Design We performed metabolome, single-cell RNA sequencing and spatial transcriptome on paired mucosal and submucosal tissue from the strictured and adjacent non-strictured intestinal segments. The candidate metabolite and metabolic enzymes were verified in primary human intestinal myofibroblasts (HIMFs) and dextran sulfate sodium-induced intestinal fibrotic mice. Next, we identified fibrosis-associated circPLCE1 to regulate the pentose phosphate pathway (PPP) using the circRNA transcriptome. Finally, we studied the functions and mechanisms of circPLCE1 using metabolome, transcriptome, metabolic flux, seahorse assay and RNA pull-down assay in HIMFs and fibroblast-specific circPLCE1 knockdown mice. Results Multilayer integrated analysis identified activation of PPP in fibroblasts during intestinal fibrosis of CD. Specifically, xylulokinase (XYLB)-generated xylulose-5-phosphate (Xu5P) promoted extracellular matrix synthesis by epigenetic upregulation of collagen transcription. Moreover, downregulation of circPLCE1 in fibroblasts activated PPP, resulting in increased glycolysis, nicotinamide adenine dinucleotide phosphate production and aggravated intestinal fibrosis in vitro and in vivo. Mechanistically, circPLCE1 directly bound the domain-I of XYLB and competitively inhibited its enzymatic activity. Decreased circPLCE1 restored XYLB activity and accumulation of Xu5P in intestinal fibrosis. Conclusion Our findings delineate a circPLCE1/XYLB/Xu5P axis in fibroblasts which orchestrates PPP and fibrogenesis, unveiling a novel therapeutic target for intestinal fibrosis of CD.

Background Excessive dietary salt disrupts the gut microbiota and is increasingly recognized as a contributor to the rising prevalence of chronic inflammatory diseases. In Crohn’s disease (CD), Western dietary patterns and gut microbiome dysbiosis are well‑established drivers of disease incidence. Identifying modifiable dietary factors, such as high salt intake, is therefore critical for developing improved preventive and therapeutic strategies. However, the precise effects of high-salt diets (HSDs) on the luminal electrolyte profile, the gut microbiome, and subsequent susceptibility to intestinal inflammation, however, remain poorly defined. Results Using a treatment‑naïve cohort, we show that CD patients exhibit a distinct fecal electrolyte profile characterized by elevated Na⁺ and reduced K⁺, which correlates with markers of both gut and systemic inflammation. Relative and absolute quantification further reveal increased abundance of the halophilic archaeon Halorubrum and a corresponding decrease in Methanobrevibacter . Systematic profiling of salt‑stress associated functional genes, including those involved in K⁺ transport, compatible solute transport and biosynthesis, revealed that the CD gut microbiome is enriched with salt stress response genes. A similar enrichment trend was observed in industrialized populations compared to the Hadza hunter‑gatherer communities. Phylogenetic and growth assays demonstrated that these genetic determinants are more prevalent in opportunistic pathogens, which consequently exhibit greater resistance to growth inhibition under high Na⁺ conditions. Indeed, using high‑salt selective media, we isolated salt‑tolerant opportunistic pathogens from colonic biopsies of CD patients. Through in vivo fecal microbiota transplantation, we demonstrate that a high‑Na⁺ adapted microbial community exacerbates colitis. Salt tolerance and its associated pathogenicity vary across strains. The E. coli CD09 isolate from CD patients exhibited greater salt tolerance than the model strain E. coli MG1655, and mice inoculated with CD09 developed more severe colitis. Conclusions Collectively, our findings elucidate a mechanism by which HSDs exacerbate intestinal colitis through restructuring of the gut microbial community. A high‑Na⁺ luminal environment drives microbial adaptation toward salt tolerance, amplifies virulence at both the community and single‑strain levels, and ultimately exacerbates colitis. Thus, the gut microbiota represents a promising therapeutic target for preventing and mitigating salt‑associated chronic inflammatory diseases.

Intestinal fibrosis, a hallmark complication of Crohn’s disease (CD), frequently progresses to stricture formation and surgical intervention. Fibroblast metabolic reprogramming is important in organ fibrosis. However, its role in intestinal fibrogenesis of CD remain elusive. We aim to explore the metabolic reprogramming of fibroblasts and its upstream regulators during intestinal fibrosis of CD. We collected paired mucosal and submucosal tissue from both stenotic and adjacent non-stenotic regions of the same CD patient. These samples underwent non-targeted metabolome, transcriptome, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomic analysis. Primary human intestinal mucosal fibroblasts (HIMFs) were isolated, and a dextran sulfate sodium (DSS)-induced mouse model of intestinal fibrosis was established for functional validation of screened key metabolites and metabolic enzymes. Finally, we employed an integrated approach including targeted metabolomics, transcriptomics, metabolic flux analysis, Seahorse extracellular flux analysis, ChIP-seq, and ATAC-seq in HIMFs and the mouse intestinal fibrosis model to verify the upstream regulatory mechanisms of the identified metabolites and enzymes. Integrated multi-omics analysis revealed that activation of the pentose phosphate pathway (PPP) in fibroblasts is a key metabolic feature of CD-associated intestinal strictures. The PPP metabolite xylulose-5-phosphate (Xu5P) was significantly upregulated in CD stenotic tissues, showed the most prominent differential expression, and strongly correlated with clinical parameters of intestinal stricturing. Both in vitro and in vivo experiments confirmed that Xu5P promotes extracellular matrix synthesis and exacerbates intestinal fibrosis by upregulating collagen transcription via epigenetic mechanisms. Furthermore, the upstream metabolic enzyme xylulokinase (XYLB) was found to activate the PPP, enhance glycolysis, increase NADPH production, and thereby intensify the intestinal fibrotic process. This study elucidates that the XYLB/Xu5P axis in fibroblasts exacerbates intestinal fibrosis in CD by activating the pentose phosphate pathway, providing a novel therapeutic target for CD-associated intestinal strictures. Conflict of interest: Dr. Zhou, Longyuan: All authors declare no competing interests. Chen, Minhu: I have received speaker honoraria from Takeda China, Xian Janssen, and AbbVie China, as well as research funding from Takeda (China). Mao, Ren: None