Search Results (1,002)

Ulcerative colitis is a chronic inflammatory bowel disease characterized by mucosal barrier disruption, dysregulated immune responses, and gut microbial imbalance. However, limitations of current therapies highlight the need for safe probiotic interventions. This study evaluated the preventive effects of fermented yak milk-derived Lacticaseibacillus paracasei CD12-1 on dextran sulfate sodium (DSS)-induced colitis in mice. The results showed that DSS caused body weight loss, an increased disease activity index, colon shortening, and severe histopathological injury. CD12-1 alleviated these abnormalities with differential effects across doses. The low-dose treatment produced the most comprehensive improvements in histopathological damage, goblet cell abundance, tight junction integrity, inflammatory cytokines, and short-chain fatty acids, whereas the high dose more effectively attenuated body weight loss. CD12-1 increased colonic ZO-1 and Occludin expression, reduced IL-1β, IL-6, and TNF-α levels, and increased IL-10. The low dose also elevated acetate and butyrate levels. Gut microbiota analysis showed that CD12-1 was associated with changes in the relative abundances of Lactobacillus, Bifidobacterium, Allobaculum, Akkermansia, and several inflammation-associated taxa. Correlation analysis associated Lactobacillus and Allobaculum with milder disease and improved barrier-related indicators, whereas Bacteroides and Sutterella were associated with greater disease severity and inflammation. Overall, CD12-1 alleviated DSS-induced colitis by improving intestinal barrier integrity and inflammatory homeostasis, accompanied by changes in microbial composition and short-chain fatty acid production. Full article

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a chronic disorder characterized by persistent intestinal inflammation. Although corticosteroids such as prednisolone effectively control disease symptoms, prolonged treatment is associated with severe side effects, including immune suppression and metabolic disturbances. To enable site-specific drug delivery, four phospholipid–linker–prednisolone conjugates were designed and synthesized as prodrugs targeting the overexpression of phospholipase A₂ (PLA₂) in inflamed intestinal tissues. The conjugates were prepared using a reversed synthetic strategy, in which the phospholipid–linker scaffold was assembled before drug coupling. The effect of spacer length on molecular conformation and predicted structural determinants of enzymatic activation was investigated through in silico analysis. Molecular docking simulations performed using the AutoDock Vina v1.2.7 framework, followed by structural and distance analysis in UCSF Chimera and 50 ns molecular dynamics simulations in GROMACS, suggested that linker length may influence ligand orientation, conformational orientation, ligand stability, and the spatial positioning of the ester bond relative to the catalytic histidine residue within the PLA₂ active site. Among the two conjugates examined in detail by molecular dynamics, C6 maintained comparatively lower ligand mobility and a shorter average distance to the catalytic residue His47 than C12. These computational findings provide structural insights that may guide the future design and optimization of phospholipid-based corticosteroid prodrugs for targeted IBD therapy. 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

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic immune-mediated condition with substantial global burden and rising incidence, requiring an expanding range of advanced therapies. This focused narrative review examines the mechanistic rationale, comparative clinical evidence, and translational implications of approved and emerging targeted therapies for adult IBD. A structured literature search was conducted in PubMed, Scopus, and Web of Science for publications from January 2021 to March 2026. Thirty-eight articles were selected as the core evidence set with landmark trials and clinical guidelines added when needed for historical or practice context. Evidence was synthesised narratively, with an explicit distinction between direct head-to-head comparisons, placebo-controlled trials, indirect network comparisons, and observational data. In UC, VARSITY showed higher week-52 clinical remission and endoscopic improvement with vedolizumab than adalimumab; in CD after anti–tumour necrosis factor (anti-TNF) failure, SEQUENCE showed risankizumab noninferior to ustekinumab for week-24 clinical remission and superior for week-48 endoscopic remission. Agents targeting tumour necrosis factor-like cytokine 1A (TL1A) have shown encouraging activity in phase 2/2b trials, but long-term effectiveness and safety remain uncertain. The current evidence supports mechanism-informed rather than biomarker-defined treatment selection. Confidence in comparative conclusions is greatest when supported by direct randomised evidence, whereas observational and indirect comparisons require caution because of confounding, heterogeneity, and differences in populations and outcome definitions. Clinical translation therefore requires the integration of the disease phenotype, prior treatment exposure, safety risks, and patient preference, with objective reassessment after therapy initiation. Full article

Background: Safe treatment options for ulcerative colitis, a chronic relapsing inflammatory bowel disease, remain limited, and the bioactive fraction of Rosa davurica Pall. root associated with its protective activity against Ulcerative colitis (UC) has not been characterized. Methods: This study evaluated the protective effects of the total root aqueous extract (WRP) and two process-defined fractions prepared by ethanol precipitation: the supernatant fraction (SRP) and crude polysaccharide precipitate fraction (PRP). These fractions were administered concurrently with Dextran sulfate sodium (DSS) during acute colitis induction in mice. Assessments included disease activity index, colon histopathology, intestinal barrier proteins, RT-qPCR analysis, fecal metabolomics, 16S rRNA sequencing, and UHPLC-MS/MS. Results: Compared to PRP, SRP significantly alleviated DSS-induced weight loss, colon shortening, perianal bleeding, and histological injury. SRP also reduced the mRNA levels of TNF-α, IL-6, IL-1β, MPO, NF-κB, NLRP3, GSDMD, and IL-18. SRP treatment increased Claudin-1 and ZO-1 protein expression, whereas Occludin expression showed no significant change. SRP treatment was associated with shifts in fecal metabolic profiles and gut microbiota composition in DSS-treated mice, including a change in the Firmicutes/Bacteroidota ratio toward the CON group pattern. UHPLC–MS/MS profiling resulted in the tentative annotation of 68 nonredundant constituents in SRP. Conclusions: Under the present experimental conditions, SRP demonstrated protective activity in DSS-induced acute colitis and represents a potentially important bioactive fraction of the R. davurica root aqueous extract. Its protective effects were accompanied by reduced inflammatory gene expression, partial enhancement of barrier-associated protein expression, and alterations in gut microbiota composition and fecal metabolic profiles. 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

Guselkumab is a monoclonal antibody directed against the p19 subunit of interleukin-23 (IL-23), thereby preventing IL-23 binding to the IL-23 receptor. IL-23 is a key driver of immune dysregulation and chronic inflammation in inflammatory bowel disease (IBD), making selective IL-23 inhibition an established therapeutic strategy in both Crohn’s disease and ulcerative colitis. Guselkumab is the most recently approved IL-23p19 inhibitor for the treatment of both major forms of IBD. It is the first IL-23p19 inhibitor to offer a fully subcutaneous induction regimen, and preliminary phase III data has suggested potential benefits for patients with perianal Crohn’s disease. In registrational trials, there were significant improvements across multiple clinical and endoscopic endpoints in comparison to ustekinumab, although these trials were not powered for formal superiority testing. This narrative review summarises the biological rationale for IL-23 blockade, reviews the available clinical evidence, discusses practical considerations for its use, and considers its place in the landscape of IBD treatments. Full article

Sexually transmitted infections (STIs) are common and probably underreported causes of proctitis and colitis. Bacterial (chlamydia, gonorrhoea, syphilis, Mycoplasma genitalium), viral (herpes simplex virus, mpox), and amoebic (Entamoeba histolytica) pathogens can cause inflammatory proctitis or colitis, which, depending on the pathogen, can mimic inflammatory bowel disease both on endoscopy and histopathology. Rectal and colonic masses are uncommon, but important manifestations of these infections, especially with chlamydia, syphilis, and E. histolytica. Testing for HIV is important in this context, since it allows for the inclusion of opportunistic pathogens into the differential diagnosis. Chronic diarrhoea can be a feature of chronic HIV infection. Enteric pathogens, such as Salmonella spp., Shigella spp., or Campylobacter spp., can be transmitted during sex, especially during oral–anal contact (“rimming”). The most common STI, human papillomavirus, is not associated with colitis, but is important because of its causal association with genital warts and anal cancer. 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

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

Background/Objectives: Intestinal diseases are a major global health problem due to their high prevalence, chronic course, and significant impact on quality of life. Increasing attention has been given to the extra-skeletal effects of vitamin D, particularly its role in immune regulation, maintenance of intestinal barrier integrity, and modulation of the gut microbiota. The aim of this review was to evaluate current evidence regarding the role of vitamin D in immune regulation, intestinal barrier function, and the pathogenic mechanisms of intestinal diseases, including inflammatory and functional gastrointestinal disorders. Methods: A structured narrative review was conducted using the PubMed, Scopus, and Web of Science databases to identify publications addressing the role of vitamin D in intestinal diseases. The literature search was updated in May 2026 and included studies published between 2004 and 2026. The aim of this review was to summarize current evidence on the effects of vitamin D on immune regulation, intestinal barrier integrity, gut microbiota, and their clinical relevance in intestinal diseases. Results: The included studies demonstrated that vitamin D plays an important role in maintaining intestinal homeostasis through regulation of innate and adaptive immune responses, preservation of epithelial barrier integrity, and modulation of gut microbiota composition. Vitamin D deficiency was associated with impaired VDR-dependent signalling, increased intestinal permeability, dysbiosis, and enhanced pro-inflammatory immune responses, which may contribute to the development and progression of inflammatory bowel disease, Crohn’s disease, ulcerative colitis, irritable bowel syndrome, and celiac disease. Conclusions: Current evidence supports the important role of vitamin D in immune regulation, intestinal barrier protection, and maintenance of gut microbial balance. Further clinical studies are required to better understand its therapeutic potential in intestinal diseases. Full article

GNR-068 is a proposed biosimilar to the ustekinumab reference product (RP), which works through the antagonism of interleukin 12 and interleukin 23. Ustekinumab RP is used for the treatment of chronic inflammatory conditions, including certain forms of plaque psoriasis, psoriatic arthritis, Crohn’s disease, and ulcerative colitis. Objectives: The purpose of the study is to study the safety, pharmacokinetics, and immunogenicity of the ustekinumab biosimilar GNR-068 and the reference drug Stelara^® after a single subcutaneous administration in healthy male volunteers. Methods: This was an open-label, randomized, comparative, parallel-group clinical trial of the safety, pharmacokinetics (PK), and immunogenicity of GNR-068 (JSC GENERIUM) and Stelara^® (Manufacturer: Silag AG, Switzerland; RU Holder: JOHNSON & JOHNSON) after a single subcutaneous administration of 45 mg in healthy volunteers. During the trial, 146 volunteers were screened, and 122 were randomized. Results: The results showed that PK similarity was established based on 90% confidence intervals (CIs) for the ratios of geometric means of the primary endpoints of area under the concentration-time curve from time 0 extrapolated to infinity (AUC_0–∞) and maximum observed serum concentration (Cmax) being contained within the pre-specified margin of 80.00–125.00%. The incidence of total ADA was lower in the GNR-068 group compared with the reference product group. Adverse events were similar between treatment groups and consistent with the safety profile of the ustekinumab RP. Conclusions: These results indicate that GNR-068 and the ustekinumab RP share similar PK and safety profiles. Full article

Background/Objectives: Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal disorder characterized by intestinal inflammation and gut microbiota dysbiosis, but current therapies remain limited by adverse effects and suboptimal long-term efficacy. Methods: Here, using a dextran sulfate sodium (DSS)-induced mouse model of IBD-like colitis, we investigated the protective effects of Yakuchinone B (YB)—a diarylheptanoid derived from Alpinia oxyphylla with reported anti-inflammatory and antioxidant activities—against inflammatory bowel disease (IBD). Results: YB supplementation significantly alleviated colitis symptoms, as evidenced by reduced body weight loss, lower disease activity index scores, attenuated colonic shortening, and ameliorated histopathological damage. YB also decreased the colonic and serum levels of TNF-α, IL-1β, and IL-6. Microbiome profiling showed that YB restored gut microbial diversity and reshaped microbial composition, with increased abundances of Alistipes and Duncaniella and reduced overgrowth of Akkermansia. Untargeted metabolomics revealed that YB modulated colitis-associated pathways, including purine metabolism, alanine, aspartate, and glutamate metabolism, and steroid hormone biosynthesis. Targeted analysis further showed that YB increased acetate, propionate, and butyrate levels. Conclusions: These results collectively suggest that YB ameliorates DSS-induced colitis by attenuating inflammation, associated with modulation of the gut microbiota-host metabolism axis, and promoting short-chain fatty acid production, supporting its potential as a promising functional dietary candidate for IBD management. Full article

Background: Malakoplakia is a rare chronic granulomatous inflammatory disorder characterized by defective macrophage phagolysosomal activity and accumulation of Michaelis–Gutmann bodies on histopathology. It occurs predominantly in immunocompromised individuals and may mimic infectious, inflammatory, or neoplastic processes, creating significant diagnostic challenges. We describe four cases of malakoplakia occurring in distinct immunocompromised states and review the published literature to better characterize its clinical spectrum, management, and outcomes. Methods: We conducted a retrospective case series of four patients diagnosed with histologically confirmed malakoplakia at our institution. Cases occurred in the setting of liver transplantation, kidney transplantation, relapsed acute myeloid leukemia, and ulcerative colitis treated with immunosuppressive therapy. A literature review was performed using PubMed and Google Scholar to identify published cases of malakoplakia in immunocompromised hosts. Demographic, clinical, microbiological, therapeutic, and outcome data were extracted and analyzed descriptively. Results: Four patients with malakoplakia involving the gastrointestinal tract or renal allograft were identified. Clinical presentations ranged from incidental endoscopic findings and tumor-like colonic masses to recurrent bacteremia and graft dysfunction. Histopathologic examination demonstrated characteristic Michaelis–Gutmann bodies in all cases. Management included antimicrobial therapy, observation, and surgical intervention when necessary. Two patients achieved complete clinical and histologic resolution, one required transplant nephrectomy because of persistent allograft infection, and one died from progressive acute myeloid leukemia. Combined with 48 cases identified in the literature, 52 patients were analyzed. The gastrointestinal tract was the most frequently affected site (76.9%), followed by the genitourinary tract (19.2%). Malignancy (32.7%), solid-organ transplantation (26.9%), and autoimmune disease (21.2%) were the most common underlying conditions. Conclusions: Malakoplakia should be considered in the differential diagnosis of mass lesions, persistent infections, and inflammatory lesions in immunocompromised patients, particularly those with malignancy or receiving immunosuppressive therapy. Early histopathologic diagnosis is essential to distinguish malakoplakia from malignancy and guide appropriate management. Our findings highlight the heterogeneous clinical manifestations and outcomes of this uncommon condition and emphasize the importance of multidisciplinary evaluation in affected patients. Full article