Search Results (1,193)

Plasma Oncostatin M (OSM) has been proposed as a biomarker of disease activity in ulcerative colitis (UC). We evaluated OSM’s relationship with clinical, endoscopic, and histological activity across two follow-up visits, compared with fecal calprotectin (FC). One hundred UC patients were assessed at Visit 1 (baseline) and Visit 2 (12 months) for clinical (partial Mayo score), endoscopic (Mayo Endoscopic Score), and histological (Nancy Histological Index) activity, alongside plasma OSM, FC, CRP, and fibrinogen; 30 healthy controls were included for comparison. Given the marked right-skewness of OSM and FC, associations were assessed using both Pearson and Spearman correlations, and logistic regression effect sizes are reported as odds ratios per doubling of biomarker concentration (log2 scale). OSM correlated significantly with all activity measures at both visits, most strongly with histological activity (r = 0.521–0.602), but weakly or not with CRP/fibrinogen. OSM was significantly elevated versus controls at both visits (p < 0.001) and declined significantly with treatment response (Δ = −89.06 vs. +0.50 in controls, p = 0.006). FC was the dominant predictor of clinical (AUC = 0.788) and endoscopic (AUC = 0.926) remission at Visit 2, with OSM contributing little independent value; however, for histological remission, both baseline OSM and ΔOSM were independent, complementary correlates (OR = 8.43 and 9.64 per doubling, respectively; p < 0.001 for both), yielding the strongest model overall (AUC = 0.949). OSM’s discriminative accuracy improved markedly from Visit 1 to Visit 2 for endoscopic (AUC 0.695 → 0.897) and histological (AUC 0.738 → 0.927) activity. Across two follow-up assessments, OSM consistently reflected UC activity, with its strongest and most independent signal for histological inflammation, both as a concurrent correlate and—more modestly—as a genuine prospective marker independent of baseline treatment exposure. OSM’s incremental value over FC was most apparent for histological status and for stringent (MES 0) endoscopic remission, but not for conventional clinical or endoscopic remission thresholds. Full article

As a traditional Tibetan medicine and health food, the fleshy roots of Sphallerocarpus gracilis were adopted to extract polyphenol powder(PP) in this research. Using a DSS-induced colitis mouse model combined with multi-omics analysis and experimental validation, we explored the protective effects and molecular mechanisms of PP against intestinal inflammation. PP mitigated colitis-related symptoms in a dose-dependent manner, inhibited pro-inflammatory cytokines and dose-dependently reversed elevated IL-10 levels to BC group. Multi-omics data revealed that PP intervention was associated with gut microbiota remodeling, enrichment of Akkermansia muciniphila, restoration of bacterial–fungal homeostasis, and improvement of tryptophan and biotin metabolism. By suppressing HMGB1 and RAGE expression, PP blocked the AGE-RAGE-mediated inflammatory cascade. In addition, PP maintained intestinal mucosal integrity through goblet cell protection, MDA reduction, and the regulation of BAX/Bcl-2, MMP3 and MMP9. Overall, PP relieves UC by regulating gut microecology, host metabolism and the AGE-RAGE pathway, which supports the translational potential of natural polyphenols for inflammatory bowel disease treatment as a gut microecological modulator. Full article

Microbiota dysbiosis is closely associated with a wide range of human diseases, yet wet-lab validation remains costly and time-consuming. Therefore, this study aims to develop an efficient framework for predicting potential microbe–disease associations. We propose a novel predictive model, NNGCFCAE, which integrates Nuclear Norm Minimization (NNM), an enhanced Graph Convolutional Network (GCF) with an energy-based Conditional Random Field (CRF) smoothing mechanism, and a multi-channel convolutional autoencoder (CAE) with residual connections to effectively infer latent microbe–disease associations. First, we construct a heterogeneous network by integrating known microbe–disease associations with Gaussian Interaction Profile (GIP) kernels and Hamming Interaction Profile (HIP) features. Subsequently, nuclear norm minimization is applied to complete the initial association matrix, yielding a preliminary prediction score matrix. The GCF module then extracts spatial structural features of microbe and disease nodes from the network, while the CAE module further learns attribute-based representations of these nodes. Finally, the prediction score matrix, topological features, attribute features, and multi-source information are fused to form a joint representation matrix, which is used to compute the final association scores between microbes and diseases. Experiments conducted on datasets such as HMDAD and Disbiome demonstrate that NNGCFCAE significantly outperforms several state-of-the-art methods in terms of AUC and AUPR. Ablation studies and case analyses on obesity, asthma, and ulcerative colitis further demonstrate its biological plausibility, highlighting its potential for uncovering latent microbe–disease associations. Full article

Both 2′-fucosyllactose (2′-FL) and Bifidobacterium can modulate gut health; however, whether their combination provides strain-dependent protection against colitis remains unclear. This study aimed to compare the protective effects of 2′-FL alone and in combination with Bifidobacterium longum subsp. infantis M63 or Bifidobacterium breve M16V in dextran sulfate sodium (DSS)-induced colitis. Forty-eight male C57BL/6J mice were randomly assigned to six groups: negative control, DSS model control, 5-aminosalicylic acid positive control, 2′-FL, 2′-FL + M63, and 2′-FL + M16V. The interventions were administered for two weeks, with 2.5% DSS supplied in the drinking water during the second week. Colitis-related indices, colonic histopathology, inflammatory cytokines, oxidative-stress markers, intestinal barrier-associated gene expression, gut microbiota composition, lactate, and short-chain fatty acids (SCFAs) were evaluated. Compared with the model control, 2′-FL and both synbiotic combinations ameliorated colonic tissue injury and goblet-cell loss. Both combinations significantly reduced IL-1β, whereas 2′-FL and both combinations reduced IL-6 and TNF-α. The combinations also increased catalase and glutathione peroxidase activities and decreased malondialdehyde levels. 2′-FL alone increased Occludin and RELMβ expression, whereas 2′-FL + M63 showed the strongest effects on tight-junction and mucus-barrier restoration, including increased Claudin-1, Claudin-2, ZO-1, TFF3, and MUC2 expression. All 2′-FL-containing interventions increased microbial diversity, while 2′-FL + M63 increased Bacteroidota, reduced Proteobacteria, and enriched Muribaculaceae and Ruminococcaceae. Both synbiotic combinations increased lactate and all measured SCFAs; 2′-FL + M63 produced the highest acetate level, whereas 2′-FL + M16V produced the highest propionate level, and both combinations markedly increased butyrate. These findings demonstrate strain-dependent protective effects, with 2′-FL + M63 showing the greatest overall efficacy in restoring intestinal barrier function and microbial metabolism, supporting its development as a candidate functional synbiotic food formulation. Full article

(1) Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease associated with gut microbiota dysbiosis and metabolic perturbations. Although Liubao tea (LBT) has gastroprotective benefits, the precise mechanisms by which LBT extract (LBTE) alleviates UC by orchestrating microbial and metabolic homeostasis remain poorly understood. (2) Methods: A DSS-induced UC mouse model was used to evaluate LBTE efficacy. Serum pharmacochemistry, untargeted metabolomics, 16S rRNA sequencing, and targeted SCFA metabolomics were integrated to characterize absorbable active constituents, metabolic shifts, and gut microbiota landscapes. SCFA- and arachidonic acid metabolism-related targets were validated by RT-qPCR and Western blotting. PGF models and FMT were used to assess the causal role of gut microbiota in LBTE-mediated efficacy. (3) Results: LBTE preserved colon length and mucosal integrity while reducing IL-6, TNF-α, IL-1β, and oxidative stress. It enriched SCFA-producing genera and increased colonic butyric and valeric acids, activating GPR41/GPR109A signaling, upregulating ZO-1 and occludin, and strengthening the intestinal barrier. LBTE also downregulated PTGS2 and ALOX5, restored PTGS1 and CYP3A11, and inhibited NF-κB signaling. These effects were weakened in PGF mice but reproduced by FMT from LBTE-treated donors, confirming microbiota-dependent protection. (4) Conclusions: LBTE may serve as a complementary strategy for UC prevention and management. Full article

Background: Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease in which long-term maintenance of remission remains a major therapeutic challenge. Increasing evidence indicates that disruption of host–microbiome metabolic interactions, impaired production of short-chain fatty acids (SCFAs), defective epithelial energy metabolism, and intestinal barrier dysfunction contribute to disease relapse. These observations have generated interest in adjunctive metabolic strategies aimed at restoring luminal homeostasis rather than directly suppressing inflammation. Objective: This narrative review examines the biological rationale for combining pectin, a fermentable dietary fiber that promotes endogenous SCFA production, with kaolin, naturally occurring adsorbent clay, as adjunctive metabolic therapy for maintaining remission in UC. We summarize current mechanistic, experimental, and clinical evidence and discuss future translational research priorities. Evidence: Experimental studies demonstrate that pectin fermentation enhances the production of butyrate and other SCFAs, thereby improving epithelial energy metabolism, strengthening intestinal barrier integrity, and modulating mucosal immune responses. Kaolin possesses adsorptive and barrier-protective properties that may reduce luminal exposure to potentially harmful microbial products while improving stool consistency. Although direct clinical evidence supporting the combined use of pectin and kaolin in UC is currently lacking, indirect evidence derived from microbiome research, SCFA biology, dietary intervention studies, and experimental models provides a biologically plausible foundation for further investigation. Perspective: We propose that restoration of luminal metabolic homeostasis through complementary modulation of microbial fermentation and luminal environmental stabilization may represent a novel adjunctive approach for reducing relapse risk in selected patients with UC receiving conventional maintenance therapy. A conceptual framework for future randomized clinical trials incorporating clinical, endoscopic, microbiome, metabolomic, and biomarker outcomes is presented. Conclusions: Current evidence supports the biological plausibility of SCFA-directed metabolic interventions in UC but remains insufficient to justify routine clinical application of pectin–kaolin therapy. Well-designed randomized controlled trials are required to determine efficacy, safety, optimal patient selection, and mechanisms of action. By integrating advances in microbiome science, intestinal metabolism, and mucosal immunology, this review provides a translational framework for the development of inexpensive, microbiome-oriented adjunctive therapies for maintenance of remission in UC. Full article

Background: The early-life gut microbiota plays a critical role in programming intestinal barrier function and immune homeostasis, with profound implications for long-term host health. However, the effects of early-life compound probiotic intervention on the maturation of intestinal barrier function and the underlying molecular mechanisms remain incompletely understood, particularly in large-animal models relevant to human physiology. Methods: In this preclinical study, 3627 neonatal piglets—a well-established translational model for human infant gut development—were orally administered a novel compound probiotic formulation comprising Bifidobacterium longum subsp. infantis BZ, Lactobacillus plantarum LZ, and Pediococcus acidilactici PZ during early life. A total of 1512 fecal samples collected at seven time points from birth to day 180 were analyzed by 16S rRNA sequencing, and 525 samples from three developmental windows (days 10, 25, and 70) were subjected to LC-MS-based metabolomics. The candidate metabolite indole-3-lactic acid (ILA) was further mechanistically validated in a DSS-induced colitis mouse model and in IPEC-J2 cells. Results: Early-life probiotic intervention significantly enhanced intestinal barrier integrity, as evidenced by improved intestinal morphology and upregulated expression of tight junction proteins—zonula occludens-1 (ZO-1), occludin (OCLN), and Claudin-1 (CLDN1)—in the jejunum (p < 0.05). Notably, intervention at birth was more effective than post-weaning administration, and two administrations (birth + weaning) yielded superior outcomes compared with a single administration (p < 0.05). Microbiome analysis revealed enhanced microbial diversity and enrichment of beneficial genera during the juvenile-to-adult transition (p < 0.05). Metabolomic profiling identified ILA as a signature metabolite consistently elevated by probiotic supplementation. Conclusions: These findings provide evidence that early-life compound probiotic intervention is associated with improved intestinal barrier maturation, with ILA identified as a key candidate metabolite that may mediate this effect, as supported by functional validation in murine and cellular models. This provides a mechanistic rationale for probiotic-based strategies to support intestinal health in human infants during critical developmental windows. Full article

Objective: In ulcerative colitis (UC), endoscopic assessment remains central to disease monitoring, but repeated colonoscopy is invasive and resource-intensive. This study evaluated the association and discriminatory performance of the systemic immune–inflammation index (SII; platelet × neutrophil/lymphocyte) and the hemoglobin–albumin–lymphocyte–platelet (HALP; hemoglobin × albumin × lymphocyte/platelet) score for endoscopic activity in UC and explored whether azathioprine use modified these associations. Methods: Among 428 retrospectively reviewed patients with UC, 218 met the inclusion criteria. Mayo-defined activity (endoscopic score ≥ 2) and Rachmilewitz EAI-defined activity (score ≥ 4) were analyzed as separate outcomes. Laboratory parameters were compared between active disease and remission groups. Receiver operating characteristic (ROC) analyses, multivariable logistic regression, sensitivity analyses accounting for disease duration and treatment category, and azathioprine interaction analyses were performed. Results: According to the Mayo and Rachmilewitz EAI definitions, 80 (36.7%) and 150 (68.8%) patients, respectively, had active disease. For Mayo-defined activity, CRP showed the highest discrimination (AUC = 0.720), followed by SII (AUC = 0.692), whereas HALP showed limited discrimination (AUC = 0.598). In the primary multivariable Mayo model, CRP, SII, younger age, and male sex were independently associated with activity, whereas HALP and azathioprine use were not. Adding SII to CRP produced only a small numerical increase in AUC (0.720 to 0.752), and adding HALP produced essentially no further change. No significant interaction between azathioprine use and SII or HALP was identified. Conclusion: SII was associated with endoscopic activity but showed only modest discriminatory performance, while HALP had limited discriminatory and independent predictive value. CRP remained the strongest individual biomarker. SII and HALP should therefore be interpreted as adjunctive inflammatory indices rather than substitutes for established biomarkers or endoscopic assessment. Full article

Background/Objectives: Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder influenced by environmental factors including cold stress. While cold exposure exacerbates intestinal inflammation, the specific microbial metabolites linking environmental stress to colitis remain unclear. 3-Hydroxypropionate (3-HPA) is a gut microbial metabolite elevated following cold exposure, but its pathogenic role in intestinal inflammation has not been investigated. This study aimed to determine whether 3-HPA contributes to colitis progression and to characterize its effects on gut microbiota and intestinal epithelial function. Methods: We employed a dextran sulfate sodium (DSS)-induced colitis mouse model to assess the impact of cold exposure and exogenous 3-HPA administration. Paired shotgun metagenomic and metabolomic analyses were performed to evaluate gut microbial composition and metabolic outputs. Mechanistic studies using NCM460 intestinal epithelial cells were conducted to examine mitochondrial respiration and tight junction integrity under nutrient-limited conditions. Results: Cold exposure increased fecal 3-HPA levels and aggravated DSS-induced colitis, characterized by enhanced weight loss, histological damage, and immune cell infiltration. Direct 3-HPA supplementation alone was sufficient to worsen colitis severity. Multi-omics profiling revealed that 3-HPA reshaped gut microbiota composition, depleted short-chain fatty acids (SCFAs), and disrupted microbial tryptophan and bile acid metabolism. In vitro, 3-HPA impaired mitochondrial oxidative phosphorylation, reduced ATP production, and compromised tight junction organization in intestinal epithelial cells. Conclusions: These findings identify 3-HPA as a gut microbial metabolite elevated by cold exposure that contributes to colitis progression by disrupting beneficial microbial metabolism while also impairing epithelial mitochondrial function and barrier integrity. Modulating 3-HPA production or its downstream epithelial effects may represent a potential therapeutic approach for IBD exacerbated by environmental stress. Full article

Background/Objectives: Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent inflammation of the colonic mucosa, resulting from a complex interplay between epithelial barrier dysfunction, dysregulated immune responses, and alterations in the gut microbiota. Despite advances in therapeutic strategies, current treatments for UC remain suboptimal. Many conventional and biologic therapies are associated with systemic side effects due to non-specific distribution, which can limit their long-term use. Novel acting therapies are needed for ulcerative colitis. This study evaluated the efficacy of intracolonic Rifamycin SV in situ gelling formulation (CB-01-35) in a rat model of oxazolone-induced colitis. Methods: Acute colitis was induced in female Wistar rats using oxazolone. Animals were treated for three days with CB-01-35 (80 mg/kg, intracolonic), Vehicle, Asacol, or dexamethasone. Clinical parameters, colon weight, macroscopic damage score (MDS), mucosal damage area, and histological score were assessed. Results: CB-01-35 significantly reduced MDS compared with Vehicle (p < 0.05) and showed a trend toward reduced mucosal damage area (p = 0.06). Histological analysis confirmed significant improvement, with reduced leukocyte infiltration and epithelial damage. No significant effects were observed on body weight or colon weight. Comparator treatments showed limited or inconsistent efficacy. Conclusions: CB-01-35 demonstrated therapeutic activity in this preclinical model, supporting further investigation as a locally acting treatment for colitis. These findings represent an initial proof-of-concept and warrant confirmation in larger and mechanistic studies. Full article

Background/Objectives: Although the exact etiology of Inflammatory Bowel Diseases (IBD) is not yet fully understood, recent evidence suggests that both genetic and dietary factors are involved in their pathogenesis. The aim of the present exploratory study was to investigate how first-degree relatives (FDRs) of individuals with IBD perceive familial risk and the role of diet in IBD onset and prevention. Methods: A mixed methods approach was followed. A total of 103 unaffected FDRs of individuals living with IBD in Greece participated in an online questionnaire examining demographic characteristics, disease-related knowledge, risk perception, and beliefs about the role of diet in IBD. In parallel, 16 semi-structured interviews explored participants’ beliefs, self-reported dietary practices, and the factors shaping them using a framework analysis guided by the Health Belief Model. Results: Exploratory quantitative findings indicated that belief in the role of diet was associated with higher odds of self-reported family dietary changes, while belief in genetic risk was associated with lower odds of self-reported family dietary changes. The findings did not characterize the nature, maintenance, or motivation of these changes. Qualitative findings provided a deeper understanding of participants’ beliefs, highlighting that diet was mainly viewed as relevant to IBD management rather than prevention. Fear of disease onset and healthcare professional guidance were perceived as key facilitators of dietary changes. Conclusions: Our findings highlight heterogeneous beliefs regarding familial IBD risk and self-reported family diet changes, and support future research addressing balanced familial-risk communication for unaffected FDRs. Full article

Probiotic interventions for inflammatory bowel disease (IBD) have become a hot research topic in this field. However, no previous studies have investigated whether fox-derived probiotics exert therapeutic effects against colitis. The present investigation evaluated the effects of Lactiplantibacillus plantarum (syn. Lactobacillus plantarum) J3, sourced from the intestines of healthy Arctic foxes, on colitis. In an in vitro LPS-stimulated Caco-2 cell model, strain J3 exhibited prominent anti-inflammatory and antioxidant capacities, indicating potential to preserve intestinal barrier integrity. Furthermore, in an in vivo DSS-induced colitis mouse model, oral J3 supplementation markedly alleviated body weight loss, lowered disease activity index (DAI), and ameliorated histopathological lesions in colon tissues. Mechanistic analyses revealed that the J3 group displayed significantly decreased colonic levels of TNF-α, IL-1β, IL-6, MPO, PGE₂, along with downregulated COX-2 mRNA expression (p < 0.05). By contrast, the levels of IL-10, TJ protein mRNA, and MUC2 mRNA were markedly upregulated, whereas serum LPS and D-Lac concentrations were significantly reduced (p < 0.05). In an exploratory analysis of 16S rDNA and short-chain fatty acids (SCFAs) in a subset of mice, J3 treatment showed a trend toward colonic microbial remodeling, accompanied by a significant increase in short-chain fatty acid production (p < 0.05). Overall, these findings indicate that Lactiplantibacillus plantarum J3 derived from foxes may alleviate DSS-induced colitis in mice, providing a basis for future translational research. Full article

Background and Objectives: Diet is a potential modifiable risk factor for ulcerative colitis (UC). This study examined the associations of individual dietary components and combined dietary profiles with UC. Methods and Study Design: This case–control study included 157 patients with UC and 395 controls. Dietary consumption frequencies were converted into ordinal scores ranging from 1 to 4. Participants were additionally classified into four dietary profiles based on combined levels of risk-promoting and protective food consumption. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: Higher consumption of fast food (OR = 5.30, 95% CI: 3.65, 7.70), carbonated soft drinks (OR = 9.37, 95% CI: 5.78, 15.18), and spicy food (OR = 1.56, 95% CI: 1.21, 2.01) was positively associated with UC. Dairy consumption was inversely associated with UC (OR = 0.52, 95% CI: 0.33, 0.82). In sex-stratified analyses, vegetable consumption was inversely associated with UC among women only. Compared with participants with high risk-promoting/low protective food consumption, those with low risk-promoting/low protective food consumption (OR = 0.07, 95% CI: 0.02, 0.21) and those with low risk-promoting/high protective food consumption (OR = 0.08, 95% CI: 0.03, 0.17) had substantially lower odds of UC. The high risk-promoting/high protective food consumption was not associated with UC. Conclusions: Frequent consumption of fast food, carbonated soft drinks, and spicy food was associated with higher odds of UC, whereas dairy consumption was associated with lower odds. Lower consumption of risk-promoting foods, irrespective of protective food consumption, was associated with substantially lower odds of UC. Prospective studies are needed to confirm these associations. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with elusive etiology and limited therapeutic options, accompanied by potential side effects. In this study, to investigate the therapeutic potential of Antarctic krill oil (AKO) in a dextran sulfate sodium (DSS)-induced mouse colitis model, animal experiments, molecular assays, transcriptomics, metabolomics, and 16S rRNA gene sequencing were conducted. Our results revealed that supplementation of AKO significantly alleviated colitis symptoms, such as weight loss, and inflammatory responses. Moreover, multi-omics analyses demonstrated that AKO inhibited the PI3K/Akt signaling pathway, remodeled beneficial gut microbiota, and reshaped metabolite profiles associated with glycerolphospholipid metabolism. Remarkably, AKO alleviated DSS-induced colitis, accompanied by coordinated changes in the gut microbiota, metabolites, and transcriptome, which were associated with suppression of key inflammatory pathways. These findings present experimental evidence for the potential of AKO as a marine-based nutritional intervention for UC, and offer novel perspectives on microbiota-targeted therapies for inflammatory diseases. Full article

Conventional microsphere drug carriers for ulcerative colitis (UC) face challenges such as limited residence time, variable drug release, and an increased risk of systemic exposure and side effects. In this study, pH-sensitive, core–shell hydrogel microcapsules were designed and fabricated using a BUCHI B-390 microsphere preparation device via electrostatic interactions and hydrogen bonds. Olsalazine sodium was encapsulated in the microcapsules, allowing for pH-responsive drug release in colon tissue for UC treatment in mice. XRD studies demonstrated the amorphous state of the drug in the formulation. The preparation of SCO microcapsules was optimized based on the drug encapsulation efficiency and the drug loading capacity, with the S₂C₁O microcapsule having the highest drug encapsulation efficiency (59.2%) and drug loading capacity (21.3%), and the production yield was approximately 62.5%. The degradation experiment results indicated that the alginate/CMCS hydrogel shell has anti-resistant and colon-targeted properties, with minimal drug leakage under acidic conditions (0.1% release at 2 h, pH 1.2) and rapid, controlled release at colonic pH (7.4) (cumulative release of 68.7% at 12 h), protecting the drug from gastric degradation. An in vivo experiment suggested that treatment with these microcapsules in UC mice significantly reduced inflammatory markers (NF-κB p65 was reduced by 18.8% relative to the free drug group) and histological damage in UC models relative to free drug administration. The improved therapeutic efficacy is linked to precise localization in inflamed tissue, reducing systemic exposure and off-target effects. Overall, in vitro and in vivo studies demonstrated that this microcapsule system provides a promising alternative to existing UC drug delivery systems. Full article