Ulcerative colitis (UC), a primary subtype of inflammatory bowel disease, remains incompletely understood in terms of its molecular etiology. This study aimed to characterize the gene signatures associated with m6A, m7G, m5C, and m1A RNA modifications and explore their potential role in UC pathogenesis. We integrated three GEO datasets and, via LASSO regression, random forest, and SVM-RFE algorithms, identified three core differentially expressed RNA methylation-related genes (DERMGs): upregulated IFIT5 and MSI2 and downregulated NCBP1. These biomarkers showed diagnostic capability in the training cohort, with area under the curve (AUC) values above 0.75. The nomogram incorporating all three markers achieved an AUC of 0.947, with robust performance maintained in both the testing set and an additional external validation cohort. Functional enrichment analysis revealed that IFIT5 and MSI2 expression was positively correlated, whereas NCBP1 expression was inversely correlated with key inflammatory pathways, such as TNFA signaling via NF-κB, the inflammatory response, IL6/JAK/STAT3 signaling, and apoptosis. Immune infiltration assessment revealed that the expression of the core DERMGs was primarily associated with T cell subsets, as further supported by partial correlation analysis controlling for inflammatory burden. In addition, changes in the expression of these genes corresponded with clinical remission after treatment with infliximab or vedolizumab. In vitro experiments confirmed that LPS stimulation upregulated IFIT5 and MSI2 and downregulated NCBP1 in NCM460 and Caco-2 colonic epithelial cells. Collectively, these findings highlight the involvement of RNA methylations in UC pathogenesis and suggest IFIT5, MSI2, and NCBP1 as potential diagnostic and therapeutic targets.

Individuals with inflammatory bowel disease (IBD) are at increased risk of herpes zoster (HZ). Using a matched cohort design, we evaluated the vaccine effectiveness (VE) of recombinant zoster vaccine (RZV) against HZ among IBD patients aged ≥18 years. Within the Kaiser Permanente Southern California population, individuals who received 2 RZV doses were matched up to 1:3 to RZV-unvaccinated individuals. Individuals were followed from 31 days after the receipt of the 2nd RZV dose until the occurrence of a censoring event. VE was calculated using Cox proportional hazards regression. A self-controlled case series analysis was used to compare the rate of flares in the 30‑day risk window following vaccination with the comparison window among RZV recipients using conditional Poisson regression. The adjusted VE of 2 RZV doses (≥4 weeks apart) against HZ was 65.4% (95% confidence interval [CI]: 40.6%-79.9%) in all IBD patients, 62.7% (17.2%-83.2%) in ulcerative colitis patients, and 70.2% (34.5%-86.4%) in Crohn's disease patients. The VE of 2 doses administered 4 weeks-6 months apart in IBD patients was 62.9% (34.3%-79.1%). The rate ratio for IBD flares was 0.80 (95% CI: 0.58-1.12). In conclusion, RZV provided protection against HZ in IBD patients with no increased risk of IBD flares observed.

Diet is increasingly recognized as both an environmental determinant and a therapeutic target in inflammatory bowel disease (IBD), yet dietary guidance for clinicians has historically been inconsistent and, in many cases, excessively restrictive. This narrative review synthesizes current evidence-based dietary recommendations for the management of IBD across disease phases, anchored on the European Crohn's and Colitis Organization (ECCO) 2025 Dietary Management Consensus and supplemented by landmark randomized controlled trials, systematic reviews, meta-analyses, and consensus guidelines published through September 2025. The ECCO 2025 Dietary Management Consensus (published September 2025) and select regional Saudi guidelines published after the initial literature search were incorporated as pre-specified anchor references given their direct relevance to this review's framework. No single IBD diet is universally applicable. During active Crohn's disease (CD), exclusive enteral nutrition (EEN) has the strongest evidence for inducing remission, while the Crohn's Disease Exclusion Diet with Partial Enteral Nutrition (CDED + PEN) offers an evidence-based, food-based alternative, particularly for biologic-naive patients. Specific dietary modifications are warranted in patients with fibrostenotic strictures. During remission, dietary fiber is associated with a lower relapse risk, the Mediterranean dietary pattern supports remission maintenance in ulcerative colitis (UC), and partial enteral nutrition may sustain remission in CD. Dietary fiber and dairy products do not require routine restriction; ultra-processed foods and excessive red meat intake should be reduced. Micronutrient deficiencies - affecting more than 50% of IBD patients - require systematic monitoring and targeted supplementation rather than empirical universal supplementation. Multiple prevalent dietary misconceptions lack scientific support and cause measurable nutritional harm if left uncorrected. Evidence-based dietary management of IBD requires individualized, phase-specific recommendations, access to IBD-experienced dietitians, and systematic micronutrient monitoring. Gastroenterologists are well-positioned to translate this evidence into meaningful clinical practice for their patients. As a narrative review, this work is subject to inherent methodological limitations, including potential selection bias in the literature and the absence of formal quality assessment of individual studies.

Responding to Miyatani et al., this commentary, focused on the United States. We contend that handheld intestinal ultrasound reframes the point-of-care debate regarding timing and cost, not diagnostic superiority. For many pediatric inflammatory bowel disease programs, bridging with radiology while building training and governance remains the wisest near-term approach.

Hyperactivated M1 macrophages with excessive reactive oxygen species (ROS) exacerbate intestinal inflammation, driving the progression of inflammatory bowel diseases (IBDs), for instance, ulcerative colitis. Current standard treatments for IBDs show limited efficacy and off-target side effects. Herein, we develop an oral, drug-free hyaluronic acid (HA)-based therapeutics that could self-assemble in aqueous solution, accumulate in inflamed colons and attenuate M1-like activation, thereby rebalancing the colonic immune landscape. Such drug-free therapeutics are generated by the conjugation of unsaturated fatty acids to HA via dynamic covalent boronate-catechol ester bonds. Mechanistically, the nano-assemblies (termed uhNAs) effectively scavenge ROS, dampen NF-κB signaling, and diminish pro-inflammatory cytokines in M1-like phenotypes. In DSS-induced acute colitis, oral uhNAs treatment elicits significant decreases in M1-like macrophages, CD8[+] T cells, and neutrophils with concomitant increases in Tregs. In chronic and relapsing DSS colitis, uhNAs also confer robust protection, supporting sustained colonic immune remodeling during recurrent intestinal inflammation. Single-cell RNA-sequencing corroborates these shifts and maps the myeloid, B and T-cell programs, highlighting the downregulated inflammatory responses following uhNAs treatment. Notably, uhNAs-OA outperform physical HA (or HA-PBA)/oleic-acid mixtures, and two clinically established IBD drugs (5-aminosalicylic acid and dexamethasone), protecting mice models against both acute and chronic colitis.

Sphingosine-1-phosphate (S1P) signaling is a bona fide drug target as evidenced by the S1P receptor modulator drug class for treating multiple sclerosis and ulcerative colitis. Despite this clinical success, on-target adverse events have been reported. To circumvent these, we hypothesized that interdicting the S1P transport cascade will have the same physiological benefits without undesired events. This led to the first reported S1P release inhibitor (SRI), SLF1081851, that supported this concept. Subsequent structural improvements led to new generations of SRIs. Herein, we report a structure-activity relationship study of novel indazole compounds inspired by modifications on a previously reported scaffold. Studies revealed compounds 6c (IC50 = 651 ± 3 nM) and 6k (IC50 = 719 ± 50 nM) to be viable SRIs with molecular modeling suggesting that conformational effects are observed and potency can be influenced by these effects. Thus, both 6c and 6k provide valuable insight into the chemical space within Spns2 and help influence the next generation of SRIs.

This prospective paired-sample study evaluated fecal calprotectin changes after polyethylene glycol-based bowel preparation in ulcerative colitis patients in remission. Calprotectin increased modestly, particularly in patients with Mayo 1 endoscopic subscore, but clinical worsening was uncommon and healthy individuals showed no significant change.