Ulcerative colitis (UC); as one of the inflammatory bowel diseases (IBD), arises from chronic inflammation of the intestinal tract. In this study, we addressed the possible protective mechanisms of vonoprazan, as a potassium-competitive acid blocker, on dextran sulfate sodium (DSS)-mediated UC. Therefore, male BALB-c mice administered oral vonoprazan (10 or 20 mg/kg/day) for 10 days and received drinking water containing 3% w/v DSS for 7 days from day 4. Vonoprazan exhibited a promising effect against UC by increasing mice body weight, colon length, and spleen weight, decreasing serum C-reactive protein (CRP) concentration and the disease activity index (DAI), and alleviating colonic histopathological changes. Colonic tissue antioxidants increased significantly in vonoprazan-treated groups. Additionally, colonic tissue oxidative stress was significantly ameliorated in vonoprazan-treated mice. Furthermore, vonoprazan preserved the integrity of intestinal mucosal barrier function and attenuated UC by decreasing the levels of immuno-inflammatory cells, inflammation-related proteins, and pro-inflammatory cytokines, elevating the tight junction proteins levels, and ameliorating mitochondrial energy metabolism. Taken together, vonoprazan protected against DSS-mediated UC in mice via antioxidant and anti-inflammatory activities that maintained tight junction architecture.

Extraction methods significantly affect the physicochemical characteristics and biological activities of polysaccharides. This study compared the effects of five extraction techniques (hot water, acid, alkali, enzyme and ultrasound-assisted extraction) on the physicochemical characteristics of Salvia miltiorrhiza polysaccharides (SMPs, SMP-W, SMP-A, SMP-B, SMP-E and SMP-U) and their protective effects against ulcerative colitis (UC) in mice. The extraction methods significantly affected polysaccharide yield, molecular weight distribution, monosaccharide composition and uronic acid content. SMP-W exhibited the lowest yield (13.06%) but the highest molecular weight (1571.40 kDa) and uronic acid content (7.57%), along with a Congo red λmax red shift suggestive of triple-helix-like features. SMP-U showed the highest yield (18.56%) but lower molecular weight (1053.18 kDa) and uronic acid content (1.13%). SMP administration was associated with barrier repair, anti-inflammatory and antioxidant effects, and gut microbiota - tryptophan metabolism remodeling. Specifically, SMP-W was closely associated with intestinal barrier repair, tight junction protein restoration, and IL-10 promotion, whereas SMP-U showed a stronger association with restored microbial diversity, pro-inflammatory cytokine suppression and oxidative stress alleviation. Correlation analysis indicated that SMP administration was associated with enrichment of beneficial Akkermansia and Lachnospiraceae, inhibition of Desulfovibrio, and a shift of tryptophan metabolism from the pro-inflammatory kynurenine pathway toward beneficial metabolites. These findings suggest that the extraction method influences SMP bioactivity, likely through alterations in molecular weight distribution and monosaccharide composition, offering a comparative basis for their application as functional food ingredients.

Disrupted membrane lipid homeostasis is implicated in epithelial barrier dysfunction and inflammatory signaling in ulcerative colitis. Associated lipid alterations include a reduced phosphatidylcholine-to-phosphatidylethanolamine (PC/PE) ratio and accumulation of lysophosphatidylcholine (LPC) and ceramide. Although oleic acid (OA) has shown protective effects in experimental colitis, its therapeutic utility is limited by rapid metabolic turnover. We therefore tested whether 2-hydroxyoleic acid (2-OHOA), a synthetic hydroxylated OA derivative with enhanced metabolic stability, protects against intestinal inflammatory injury. In IFN-γ/TNF-α-stimulated Caco-2 monolayers, 2-OHOA pretreatment preserved epithelial barrier function, attenuated the increase in membrane fluidity, and reduced STAT3 and NF-κB activation, whereas OA at the same concentration provided little protection. In a dextran sulfate sodium (DSS)-induced murine colitis model, 2-OHOA pretreatment attenuated weight loss, disease activity index, colon shortening, and reduced the spleen index and histological injury scores, whereas OA at the same dose had minimal effects. 2-OHOA also attenuated colonic induction of Il-1β, Il-6, and Tnf-α expression and partially preserved occludin protein levels. Lipidomic analysis showed attenuation of DSS-induced PC depletion, shifts in the PC/PE and LPC/PC ratios, and ceramide and hexosylceramide accumulation. In cytokine-challenged Caco-2 cells, knockdown of the PC biosynthetic enzyme CCTα limited PC preservation by 2-OHOA, while PC(34:1) supplementation attenuated barrier dysfunction, supporting a functional contribution for PC homeostasis to epithelial protection. Together, these findings support preventive effects of 2-OHOA in experimental colitis, accompanied by preservation of lipid homeostasis and epithelial barrier function and reduced inflammatory signaling.

Hepatic steatosis is among the most frequent hepatobiliary abnormalities in inflammatory bowel disease (IBD), but its clinical interpretation is increasingly complex. This narrative review provides evidence-based guidance for gastroenterologists managing adults with IBD and hepatic steatosis. Cohort and meta-analytic evidence indicates that hepatic steatosis affects approximately one-quarter to one-third of patients with IBD, although estimates vary according to diagnostic method, population selection, disease phenotype, metabolic burden, and study design. Metabolic dysfunction-associated steatotic liver disease (MASLD) provides a useful framework for patients with cardiometabolic dysfunction, but a steatosis-centered approach is more inclusive in IBD because it accommodates lean or undernourished patients, inflammation-associated phenotypes, ileal or bile acid-related mechanisms, alcohol overlap, medication-related vulnerability, and mixed presentations. The main clinical priority is not merely to detect liver fat, but to identify meaningful fibrosis, cardiometabolic risk, and modifiable contributors. Normal aminotransferases do not exclude steatosis or fibrosis. Screening should be risk-based rather than universal. Fibrosis-4 index can be used pragmatically for initial triage in stable adults, but its IBD-specific limitations require cautious interpretation; transient elastography is most useful as a secondary fibrosis assessment or as a combined first test when readily available. Follow-up should be driven by fibrosis and cardiometabolic risk rather than by IBD alone, and hepatology referral should be reserved for elevated liver stiffness, persistent or cholestatic liver-test abnormalities, portal-hypertension features, suspected alternative liver disease, discordant tests, or clinically significant hepatic dysfunction. Hepatic steatosis alone should not determine IBD drug selection, although liver dysfunction and treatment-specific hepatotoxicity may modify monitoring or therapeutic choices.

Currently, there are still no reliable pre-treatment biomarkers for vedolizumab in ulcerative colitis. To investigate baseline mucosal signals, we reconstructed the discovery cohort from GSE73661 and evaluated the derived panel in the blood samples from GSE191328 and the independent mucosal RNA-seq cohorts from E-MTAB-7845. The reconstructed cohort comprised 24 baseline samples, including 14 composite responders and 10 non-responders. Through repeated LASSO variable selection, the study identified an exploratory gene set consisting of ZNF689, TPRXL, ZC3H10, and MRPL55. The selection procedure yielded a mean held-out AUC of 0.611 across 18 complete nested-validation repetitions; this does not independently validate the final gene set. When the fixed gene set was projected exploratorily, the AUC for 17 blood samples was 0.458 (95% CI 0.162-0.755), and the AUC for 27 independent UC mucosal samples was 0.534 (95% CI 0.293-0.775). The apparent AUC of this gene set on the discovery set was 1.000, and 500 full-process bootstrap analyses indicated that gene selection was unstable. Among the three targeted inflammatory panels, interferon-γ showed a directional difference that was not statistically significant (mean GSVA score difference -0.425; nominal P = 0.066; adjusted P = 0.197). Expression scales and clinical endpoints differed across cohorts. The above results describe post-selection separation within the discovery cohort and do not establish reproducible predictive performance, tissue specificity, or a definitive four-gene signature.

Sanghuangporus sanghuang (Sanghuang) extract, obtained from the medicinal and edible fungus Sanghuang, was examined for its inhibitory effects against Candida albicans and its potential role in mitigating intestinal inflammation related to ulcerative colitis (UC). Its anti-Candida albicans activity was assessed by measuring the minimum inhibitory concentration (MIC), evaluating its ability to suppress biofilm formation, and observing fungal morphological changes using scanning electron microscopy (SEM). Using mice with dextran sulfate sodium (DSS)-induced UC and intestinal Candida albicans (C. albicans) colonization, fungal burden, intestinal inflammation, mucosal injury, intestinal bacterial community composition, and related signaling pathways were assessed. Sanghuang extract inhibited C. albicans growth and suppressed biofilm formation. SEM further revealed reduced hyphal development and disruption of cell surface morphology following treatment. In vivo, Sanghuang administration ameliorated UC-related phenotypes, with descriptive decreasing trends in fecal C. albicans burden, less severe colonic injury, and lower colonic levels of IL-6, IL-1β, and TNF-α, accompanied by changes in intestinal bacterial community composition. Network pharmacology analysis suggested that pathways associated with phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) may participate in this process. Molecular docking yielded predicted interactions of caffeic acid with PTGS2, EGFR, PIK3CA, AKT1, and mTOR. qRT-PCR further showed that Sanghuang extract reduced the colonic mRNA expression of Pik3ca, Akt1, and Mtor. These findings provide experimental evidence that Sanghuang extract exerts antifungal activity in vitro and is associated with changes in fecal C. albicans burden and colitis-associated inflammatory responses in this mouse model.

Marine-derived polysaccharides have emerged as promising bioactive candidates for alleviating ulcerative colitis (UC), a chronic inflammatory bowel disease with limited therapeutic options. This review systematically summarizes recent advances in the sources, preparation methods, structural features, and multi-target mechanisms of these polysaccharides from seaweeds, marine animals, and microorganisms. Key physicochemical parameters, including molecular weight, monosaccharide composition, glycosidic linkages, and sulfation patterns, critically influence their anti-colitis efficacy. Mechanistically, these macromolecules synergistically restore gut microbiota homeostasis (e.g., promoting short-chain fatty acids and secondary bile acids), suppress inflammatory pathways (NF-κB, MAPK, and NLRP3), regulate immune responses (inhibiting dendritic cell and Th1/Th17 activation), alleviate oxidative stress via the Nrf2/HO-1 pathway, and reinforce intestinal epithelial barrier integrity (upregulating tight junction proteins and mucins). Although systematic toxicological characterization remains limited, the generally favorable safety profiles reported in preclinical studies, together with their multi-target nature, suggest that marine polysaccharides hold great potential as functional foods or adjunctive therapies for UC. However, challenges remain in structural heterogeneity, batch-to-batch consistency, and limited clinical validation. Future efforts should prioritize structure-activity relationship elucidation, advanced analytical characterization, bioavailability and gastrointestinal fate studies, standardization and quality control, comparative evaluation against conventional therapies and other natural products, and well-designed clinical trials to facilitate translation from bench to bedside.

Inflammatory bowel disease (IBD) is a relapsing-remitting inflammatory disorder of the gastrointestinal tract driven by dysregulated T helper (Th)-cell responses, gut microbiota imbalance, and altered bile acid metabolism. While cholic acid (CA), a primary bile acid, is immunotoxic at high concentrations, its immunomodulatory role at physiological levels remains unclear. Here, we evaluate the therapeutic potential of CA in an experimental colitis model. Administration of biologically tolerable CA significantly reduced disease activity, preserved colon length, and alleviated histological inflammation. Mechanistically, CA downregulated RORγt levels and promoted Th cell plasticity toward IL-10-producing phenotypes, resulting in diminished production of IFN-γ and IL-17. Dietary depletion of primary bile acid precursors and IL-10 neutralization confirmed IL-10-dependent immunoregulation as a key mechanism. Additionally, synthetic derivatives of CA, similar to CA, attenuated DSS-induced colitis by selectively expanding IL-10-producing Th cells. Collectively, these findings highlight CA and its synthetic derivatives as immunomodulatory candidates for the therapy of ulcerative colitis.