Search Results (883)

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

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: 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/Objectives: Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease (IBD) lacking therapies that directly promote mucosal healing, an important clinical endpoint and therapeutic goal for achieving remission and improved long-term outcomes. Epithelial restitution is a key component of effective mucosal healing. EPICERTIN, a novel biotherapeutic candidate, has previously demonstrated epithelial repair activity in dextran sulfate sodium (DSS)-induced colitis models and enhanced epithelial cell viability in human IBD colon explants. To further substantiate its therapeutic efficacy in a UC-relevant context, we evaluated EPICERTIN in acute oxazolone (OXA)-induced colitis in BALB/c mice, a model reflecting the adaptive immune-driven inflammation and histopathologic characteristics of human UC. Methods: Orally administered EPICERTIN, at escalating doses (0.3 µg, 3 µg, and 30 µg), was assessed for therapeutic efficacy in male and female mice through body weight, Disease Activity Index (DAI) scores, and histopathology. Wound healing and immune impacts were examined using qRT-PCR, Imaging Mass Cytometry (IMC), and Cytometry by Time of Flight (CyTOF) in male mice. Results: EPICERTIN effectively mitigated acute OXA-induced colitis. The 3 µg dose provided the greatest benefit, improving body weight recovery and reducing DAI and histopathological damage scores. Treatment reduced Il1b while increasing Cdh1 expression, accompanied by higher levels of epithelial markers (pan-cytokeratin (PanCK), E-cadherin, epithelial cell adhesion marker (EpCAM)) and decreased fibrotic markers (collagen type I, alpha-smooth muscle actin (α-SMA), fibronectin). Moreover, EPICERTIN reduced inflammatory lymphoid and myeloid cells while increasing γδ T cells in the colon lamina propria. Conclusions: Collectively, these results demonstrate that EPICERTIN promotes epithelial restitution, suppresses inflammation, and supports mucosal healing, substantiating its therapeutic potential for UC. Full article

Aim of the study: This study aims to isolate extracellular vesicles derived from Elaeocarpus braceanus fruits (EBDEVs) and evaluate their alleviating efficacy as nature nanoparticles against dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). Methods: EBDEVs were isolated by differential and density gradient ultracentrifugation, then characterized for morphology, size, stability, and composition. Their anti-inflammatory activity was assessed in LPS-stimulated RAW264.7 macrophages. In vivo, acute UC was induced in C57BL/6 mice by 2.5% DSS. Disease severity, intestinal barrier integrity, TLR4/MyD88/NF-κB pathway activation, and gut microbiota composition were evaluated. Results: EBDEVs exhibited a typical spherical structure and were rich in bioactive components such as lipids, flavonoids, and terpenoids. Macrophages readily internalized them and significantly inhibited LPS-induced NO production. In UC mice, EBDEVs ameliorated weight loss, colon shortening, and tissue damage, while reducing serum inflammatory cytokines. EBDEVs restored intestinal barrier function by regulating tight junction proteins. Mechanistically, EBDEVs suppressed the activation of TLR4/MyD88/NF-κB and downstream NLRP3 inflammasome inflammatory signaling cascades, and remodeled the dysregulated gut microbiota structure. Conclusions: EBDEVs alleviate DSS-induced UC in mice by repairing the intestinal barrier, inhibiting inflammatory pathways, and modulating gut microbiota. Full article

Excessive consumption of ultra-processed foods (UPFs) containing non-nutritive sweeteners (NNS) has been implicated in inflammatory bowel disease (IBD), yet the effects of erythritol on intestinal inflammation remain poorly understood. In this study, we assessed NNS-containing UPF exposure in patients with IBD and healthy controls, and then investigated the effects of erythritol in a dextran sulfate sodium (DSS)-induced colitis. Food frequency questionnaire (FFQ) results showed that patients with IBD, particularly those with active disease, had a higher proportion of NNS-containing UPF categories among total UPFs consumed. In mice, erythritol administration exacerbated DSS-induced colitis, as evidenced by sustained body weight loss, increased disease activity index, impaired intestinal barrier integrity, and elevated inflammatory cytokine expression. Transcriptomic analysis revealed significant enrichment of ferroptosis-related pathways in the colonic mucosa of erythritol-treated colitic mice. Furthermore, erythritol markedly altered gut microbial composition, characterized by increased abundance of potentially pathogenic bacteria and enrichment of Alistipes sp. CHKCI003. Untargeted metabolomics demonstrated alteration of tryptophan metabolism. Consistently, erythritol aggravated depression-like behavior in DSS-induced mice. Collectively, these findings suggest that erythritol exacerbates experimental colitis and depression-like behavior, potentially through microbiota dysbiosis, ferroptosis-associated alterations, and disrupted tryptophan metabolism. Full article

Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Current treatments, including anti-inflammatory drugs and biologics, often have limited efficacy and significant side effects, highlighting the need for novel therapeutic approaches. Phellodendrine (PHE) is a characteristic ingredient of Phellodendri chinensis, yet its effects and mechanisms on IBD remain elusive. The present study evaluated the potential of PHE for preventing dextran sulfate sodium-induced IBD in zebrafish. PHE effectively reduced inflammatory cell infiltration and modulated polarized macrophages. The qPCR results further confirmed the down-regulation of pro-inflammatory genes and up-regulation of anti-inflammatory factors. Consequently, PHE promoted the resolution of IBD inflammation. PHE also restored intestinal barrier integrity by enhancing MUC2 expression, increasing goblet cell counts, and reducing intestinal permeability of both chemical and physical barriers. In addition, PHE was associated with alterations in the gut microbiome, including a reduction in potentially pathogenic microbes and an increase in beneficial microbial populations. PHE also alleviated oxidative stress. Network pharmacology suggested the potential involvement of the IL-17 signaling pathway, the lipid and atherosclerosis pathway, and the TNF signaling pathway in the preventive effects of PHE against intestinal inflammation in the zebrafish model. In vivo gene expression analysis suggested that JUN, PTGS2, IL1B, DRD2, CALM1, and HSP90AA1 may serve as putative targets of PHE. Collectively, our results indicate that PHE demonstrates potential anti-inflammatory and barrier-protective activities in a zebrafish model of intestinal inflammation. The pharmacological mechanisms by which PHE restores intestinal barriers (microbial, chemical, physical, and immune barriers) include resolving inflammation, decreasing ROS production, and enhancing lipid accumulation in the lumen overlying the intestinal mucus barrier. This study provides novel insights into the preventive effects of PHE against intestinal inflammation in a zebrafish model, suggesting its potential as a candidate for further investigation. Full article

Ulcerative colitis (UC) is a chronic inflammatory disease characterized by persistent colonic inflammation, excessive oxidative stress, and impaired barrier function. Transition metal-based nanoparticles offer promising antioxidant platforms to address oxidative stress-related pathologies. To overcome the poor gastrointestinal stability of the potent dietary antioxidant epigallocatechin gallate (EGCG), we utilized zinc-coordinated EGCG (EGCG-Zn) nanoparticles (NPs), which function as a transition metal–phenolic network, to achieve sustained colonic release and overcome the poor gastrointestinal stability of free EGCG. The therapeutic efficacy and underlying mechanisms were evaluated in dextran sulfate sodium (DSS)-induced colitis in mice. Oral administration of EGCG-Zn NPs effectively reduced oxidative stress, suppressed pro-inflammatory cytokine production, alleviated colitis symptoms, and repaired the intestinal mucus and mechanical barriers. Mechanistically, transcriptomic analysis revealed that EGCG-Zn NPs pretreatment markedly reversed DSS-induced transcriptional alterations. Integrated K-means clustering and KEGG enrichment analyses further demonstrated that these protective effects were mediated by down-regulating inflammation-associated genes and up-regulating tight junction proteins, primarily involving the modulation of calcium signaling, T-cell differentiation, and the PI3K-Akt, Wnt, NF-κB, and TNF pathways. Collectively, these findings suggest that EGCG-Zn NPs alleviate DSS-induced colitis by mitigating inflammation, suppressing oxidative stress, and promoting epithelial barrier repair, supporting their potential as a functional nutraceutical for UC management. Full article

(1) Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain and altered bowel habits, linked to dysbiosis and inflammation. Currently available treatments, focused on symptom management, displayed limited efficacy. Recent research highlights microbiota modulation as a potential therapeutic strategy to restore intestinal barrier integrity; (2) A dextran sulfate sodium (DSS)-induced mouse model of post-colitis IBS-like symptoms was performed to evaluate the effect of a novel mixture of Enterococcus lactis SF68^®, butyrate, and folate. Disease activity index and spleen weight were assessed. Markers of gut inflammation, intestinal barrier alterations, and gut butyrate bioavailability were measured. The activity of colonic mitochondria was also analyzed; (3) Supplementation with the novel mixture significantly reduced spleen weight and cytokine levels. The intestinal epithelial barrier was restored through an increase in claudin-1, occludin, and defensin 1–3 and a reduction in LBP plasma level. Treatment with the mixture enhanced the expression of butyrate transporters in mice. Mitochondrial activity markers, including citrate synthase and Cytochrome c oxidase, were improved by treatment; (4) The novel mixture containing Enterococcus lactis, butyrate, and folate exerted a protective effect against post-inflammatory IBS by reducing local inflammation, restoring intestinal barrier integrity, and enhancing butyrate bioavailability, suggesting its potential for managing post-inflammatory IBS symptoms effectively. Full article

Gut microbiota dysbiosis and metabolic disorders are key factors in inflammatory Bowel Disease (IBD) pathogenesis and progression. Although Artemisia rupestris water extract (AR) contains many anti-inflammatory compounds, its effects and mechanisms in colitis have not yet been explored. This study is the first to evaluate AR’s therapeutic efficacy in dextran sodium sulfate (DSS)-induced colitis and to investigate whether AR acts by modifying the gut microbiota and correcting metabolic imbalances. An acute inflammatory bowel disease model was established in mice using 3% DSS. Mice received AR at different doses, and clinical and pathological indices, histopathological scores, and blood concentrations of pro-inflammatory cytokines were evaluated. We explored AR; mechanisms in IBD using 16S rRNA sequencing and untargeted metabolomics. AR decreased concentrations of pro-inflammatory cytokines IL-6, CXCL-1, and TNF-α, and reduced MPO levels. It reduced intestinal permeability and mitigated IBD symptoms. Immunohistochemistry demonstrated that AR downregulated TLR4 and TLR9, while restoring Occludin (OCC) and Zonula Occludens-1 (ZO-1). AR modified the gut microbiota by reducing aberrant taxa such as HT002 and Erysipelatoclostridium, while increasing beneficial bacteria including Bacteroides, Alloprevotella, and Lachnospiraceae_NK4A136_group. AR also rectified metabolic disturbances by reducing 5OH-HIP, reversing decreases in metabolites such as 4-(2-amino-3-hydroxyphenyl)-2,4-dioxobutanoate and vanillin, and influencing amino acid and lipid metabolic pathways. AR treatment produces therapeutic effects distinct from other interventions by targeting inflammatory responses, restoring the gut microbiota and metabolism, suppressing TLR4 and TLR9 signaling, and repairing the mucosal barrier. Full article

Background/Objectives: Watercress (Nasturtium officinale), a cruciferous vegetable rich in phenethyl isothiocyanate (PEITC) and bioactive phytochemicals, has demonstrated anti-inflammatory and cytoprotective activities in multiple disease models; however, its effects on colitis remain insufficiently characterized. In the present study, we investigated the effects of watercress extract supplementation in dextran sulfate sodium (DSS)-induced experimental colitis. Methods: Male C57BL/6 mice were fed either a standard AIN-93G diet or a diet supplemented with 0.5% (w/w) watercress extract for 4 weeks, followed by DSS administration to induce acute colitis. Colonic histopathological injury, immune responses, barrier integrity, and gut microbiota composition were evaluated. In addition, the activity of PEITC, a major bioactive constituent of watercress, was examined in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages in vitro. Results: Watercress extract attenuated DSS-induced colon shortening and reduced histopathological injury. The supplementation of watercress extract also decreased colonic immune cell accumulation, suppressed the expression of pro-inflammatory mediators, and preserved intestinal barrier integrity. The 16S rRNA gene amplicon sequencing further revealed that watercress extract reshaped gut microbial composition, including increased abundance of Monoglobus and Adlercreutzia, and reduced abundance of microbial taxa such as Enterococcus and Enterorhabdus. Moreover, PEITC suppressed LPS-induced inflammatory activation in RAW264.7 macrophages by reducing nitric oxide production, inhibiting p38 MAPK phosphorylation, and downregulating multiple inflammatory cytokines and chemokines. Conclusions: These findings demonstrate that watercress extract alleviates experimental colitis through attenuating mucosal inflammation, preserving intestinal barrier function, and modulating the gut microbiota, highlighting watercress as a promising dietary strategy for improving gut health and mitigating intestinal inflammation. Full article

Background/Objectives: Manumycin A, a natural polyketide antibiotic isolated from Streptomyces species, has been reported to exhibit anticancer, anti-inflammatory, and immunomodulatory activities through regulation of multiple signaling pathways. However, its therapeutic potential in inflammatory bowel disease (IBD) has not yet been investigated. This study aimed to evaluate the protective effects of Manumycin A in a dextran sulfate sodium (DSS)-induced colitis mouse model. Methods: Experimental colitis was induced in male ICR mice by administration of 3% DSS in drinking water for 7 days. Manumycin A (1, 5, and 10 mg/kg) was administered via intraperitoneal injection, and 5-aminosalicylic acid (100 mg/kg) was used as a positive control. Disease severity was evaluated by body weight changes, disease activity index (DAI), colon length, histopathological analysis, and immunohistochemical assessment of pro-inflammatory cytokines, including IL-1β, IL-6, TNF-α, and IFN-γ. Results: Manumycin A treatment attenuated DSS-induced colitis in a dose-dependent manner. Although body weight changes were modest and did not show statistically significant differences among groups, Manumycin A significantly reduced DAI scores compared with the DSS-treated group. Treatment also alleviated DSS-induced colon shortening and improved histopathological alterations, including epithelial damage, mucosal disruption, and inflammatory cell infiltration. Immunohistochemical analysis showed that Manumycin A reduced the expression of IL-1β, IL-6, TNF-α, and IFN-γ in colon tissues. Conclusions: Manumycin A exerted protective effects against DSS-induced colitis by attenuating inflammatory responses and improving colonic tissue damage. These findings suggest that Manumycin A may have therapeutic potential as a candidate for the treatment of IBD. Full article

Low-molecular-weight collagen peptides from food processing byproducts offer a sustainable approach to mitigating intestinal inflammation, yet their mechanistic roles remain incompletely understood. We evaluated red fish scale collagen peptides-I (LSCP-I), a <3 kDa collagen peptide fraction derived from Lutjanus erythropterus scales, in cellular and murine models of colitis. In Caco-2 cells subjected to macrophage-mediated inflammatory injury, LSCP-I (50 µg/mL) increased proliferation by 35%, enhanced migration by 40%, preserved barrier integrity, reduced reactive oxygen species (ROS) by 45%, decreased lipid peroxidation by 30%, and restored glutathione (GSH) and superoxide dismutase (SOD) activity. In mice with dextran sulfate sodium (DSS)-induced colitis, oral administration of LSCP-I at 200, 400 and 800 mg/kg/day attenuated weight loss and diarrhea, lowered intestinal permeability by 38%, enhanced colon histology, and restored the balance between pro- and anti-inflammatory cytokines. Mechanistically, LSCP-I activated the Nrf2 antioxidant pathway and partially restored gut microbiota composition. These results demonstrate that LSCP-I reinforces intestinal barrier function, restores redox homeostasis, and modulates host–microbiota interactions, establishing its potential as a functional food ingredient for the prevention and management of inflammatory bowel disease. Full article

Dextran sodium sulfate (DSS) was used to induce ulcerative colitis in a porcine model to investigate the transcriptional responses in inflamed colonic tissue. Eleven pigs were divided into two groups, of which five pigs were administered an oral dose of DSS daily for five days, whereas six non-treated pigs served as a control group. Differences in transcript expression between treated and control pigs identified 425 down-regulated and 780 up-regulated mRNAs in response to DSS treatment. Fifty-nine differentially expressed miRNAs were also identified, comprising 20 up-regulated and 39 down-regulated miRNAs. The top enrichment KEGG pathways for the up-regulated genes were breast cancer (ssc05224), gastric cancer (ssc05226), focal adhesion (ssc04510), and the PI3K-Akt signaling pathway (ssc04151). The top gene ontology terms for the up-regulated genes were blood vessel development (GO:0001568), extracellular matrix and external encapsulating structure (GO:0031012). Protein–protein interaction network analysis identified three hub genes, including LOXL1, MFAP2, and FSTL3. Seventeen high-confidence miRNA-mRNA pairs were recognized, and two genes (CD101 and AVL9) have been confirmed as targets for ssc-miR-24-3p by dual-luciferase reporter assay. Our study provides a better understanding of the key roles of mRNAs and miRNAs in regulating DSS-induced colitis in pigs and defines sets of coding and non-coding RNA transcripts, which may serve as intervention targets or biomarkers for ulcerative colitis. Full article

Inflammatory bowel disease, including ulcerative colitis (UC) and Crohn’s disease (CD), is associated with reduced vagus nerve activity and impaired barrier function. Transcutaneous auricular vagus nerve stimulation (taVNS) shows preventive effects in acute colitis, but its impact on intestinal barrier integrity remains unclear. To assess this, C57BL/6 male mice received taVNS (10 V, 20 Hz, 500 µs, 10 min) prior to colitis induction. UC-like colitis was induced using 5% dextran sulfate sodium (DSS) for 120 h with daily taVNS, while CD-like colitis was induced by intrarectal dinitrobenzene sulfonic acid (DNBS, 4 mg) in 30% ethanol with taVNS during induction and for 48 h. TaVNS reduced colonic proliferation in non-colitic mice in a homeostatic manner, as well as in DNBS-colitic mice, and enhanced differentiation. It decreased enteroendocrine cells in non-colitic conditions but not in DSS-colitic mice, and reduced tuft cells in DSS and DNBS groups. TaVNS increased MUC2 in DSS colitis and decreased TFF3 in DNBS controls. It decreased Lgr5⁺ stem cells in DSS controls but maintained them during DSS colitis, while HOPX⁺ stem cells decreased in non-colitic DSS conditions, and fetal-like stem cells remained unchanged. Disease activity index negatively correlated with chromogranin A. TaVNS prevented increased paracellular permeability in the distal colon of DSS-colitic mice, increased TEER in distal DSS controls and proximal colitic colon, and enhanced ion transport in the proximal colon under non-colitic DSS conditions. Overall, taVNS effects on epithelial composition and barrier function are context- and model-dependent. Full article