Search Results (224)

This study evaluated the effects of oligomeric ultrafine-nano hydrogen water (OUHW) on production performance, egg quality, egg nutrient deposition, systemic metabolism, intestinal barrier function, and reproductive status in late-laying hens. Unlike conventional hydrogen-rich water, which primarily delivers molecular hydrogen dissolved in water, OUHW integrates oligomeric water with ultrafine-nano-sized hydrogen bubbles, providing a distinct physicochemical form of hydrogen-water intervention. A total of 288 healthy 67-week-old Jingfen No. 8 laying hens were assigned to 2 treatments with 6 independent replicates per treatment (24 hens per replicate) and provided with either tap water or OUHW for 11 weeks. Compared with the control, OUHW reduced the feed conversion ratio and the rates of manure-spotting while increasing the laying rate, qualified egg rate, and total egg number during weeks 5–8 (p < 0.05). These productive and egg quality improvements were phase-specific effects observed in the late laying stage during the 11-week trial. At week 4, OUHW significantly increased egg weight (p < 0.05). At week 8, OUHW also improved eggshell compressive elastic deformation, eggshell thickness, albumen height, and Haugh unit (p < 0.05). At week 6, eggs from OUHW-treated hens had higher concentrations of glutamate, glycine, alanine, C18:0, C18:1n9c, C20:4n6, and C22:6n3 (p < 0.05). Serum metabolomics showed that 25 differential metabolites from the OUHW treatment group were predominantly enriched in glycerophospholipid, sphingolipid, branched-chain amino acid, histidine, and tryptophan metabolism. In the cecum, OUHW decreased p-cresol and increased isovaleric acid and acetic acid (p < 0.05). Notably, the overall community structures of the cecal and oviductal microbiota exhibited no significant treatment-related alterations, indicating limited structural changes in the microbial communities in response to the OUHW intervention. OUHW also reduced interleukin-2 and tumor necrosis factor-α, increased interleukin-10 in the jejunum and oviductal isthmus (p < 0.05), and upregulated the mRNA expression of ovarian steroidogenic acute regulatory protein and intestinal Occludin, Claudin-1, and Mucin-2 (p < 0.05). These findings indicate that OUHW improved laying performance, egg quality, and egg nutrient deposition, possibly through modulation of the metabolism, intestinal barrier function, ovarian function, and oviductal inflammation. Full article

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH), which contributes to systemic metabolic disorders. However, the mechanisms underlying CIH-induced intestinal dysfunction remain unclear. In this study, we investigated the effects of CIH on intestinal barrier integrity, gut microbiota, and host metabolism using a multi-omics approach. Male C57BL/6J mice were exposed to six weeks of CIH or normoxia. Colonic barrier integrity was assessed by histological and molecular analyses. Gut microbiota was profiled by full-length 16S rRNA gene sequencing. Untargeted metabolomics was performed on fecal and serum samples, followed by integrated microbiome–metabolome analysis. CIH markedly impaired colonic barrier integrity, as evidenced by disrupted crypt architecture, reduced goblet cell abundance, and decreased expression of ZO-1, Occludin, and Claudin-5. CIH also induced gut microbial dysbiosis, characterized by depletion of the beneficial mucin-associated bacterium Akkermansia muciniphila and enrichment of several anaerobic taxa. Metabolomic analysis revealed opposite alterations of PC (20:2/0:0) and LysoPE (20:5/0:0) between feces and serum, whereas melatonin was consistently decreased in both compartments. Integrated multi-omics analysis further revealed close associations between microbial dysbiosis and metabolic remodeling. Collectively, these findings demonstrate that CIH disrupts intestinal homeostasis through coordinated alterations in barrier integrity, gut microbiota composition, and host metabolism, providing new insights into the intestinal mechanisms underlying OSA-associated systemic dysfunction. Full article

Red tilapia (Oreochromis sp.) fry are routinely transported between hatcheries and grow out farms, yet the effects of transport duration on epidermal barrier-associated responses and goblet cells remain poorly defined. This study assessed the impact of simulated transport on epidermal morphology, immune-related gene expression and goblet cell density in red tilapia fry. Fish were assigned to four groups (0, 5, 12 and 20 h of transport). Skin samples were analyzed for relative mRNA expression of 10 genes associated with tight junction proteins, mucins, antimicrobial peptides and cytokines using RT-qPCR, and for epidermal goblet cell density by histology. Transport significantly modulated eight genes, forming three co-expression clusters associated with inflammatory, barrier-related, and mucus-related responses, with mainly non-linear time courses. MUC2, DB-4, IL-1β, and TGF-β1b showed transient increases at 5–12 h, whereas MUC5AC and claudin transcripts increased earlier and approached control levels at 20 h. Goblet cell density remained relatively stable up to 12 h but declined after 20 h, coinciding with changes in MUC2 and MUC5AC expression and suggesting altered mucosal responses during prolonged transport. Overall, transport durations ≤ 12 h were associated with relatively stable epidermal responses, whereas 20 h induced pronounced changes in goblet cell density and barrier-associated gene expression. These findings provide information that may assist future optimization of transport practices in tilapia aquaculture. Transport stress in red tilapia fry induces rapid defensive responses, significantly modulating gene expression and mucosal dynamics; this is characterized by increased mucus production, goblet cell density, and early upregulation of mucins (MUC2), followed by later increases in tight junction genes and anti-inflammatory cytokines, alongside a temporary downregulation of antimicrobial peptides. Full article

Background: Diets high in fat and carbohydrates, like fructose, trigger colon inflammation, increase intestinal permeability, and drive dysbiosis. However, the effects of obesogenic diets on gut microbiota, including Clostridium and Bacteroides, remain unknown. Understanding how these diets damage the colon is critical. Methods: Using a controlled preclinical obesity model, we compared the effects over time of High-Fat Diet (HFD), High-Fructose Diet (HFrD), and their combination (HFHFrD). Diet-induced dysbiosis was assessed at 4 and 8 weeks via qPCR using primers specific to bacterial phyla and species. In addition, intestinal inflammation, atrophy, and mucin production were evaluated by digital pathology after 8 weeks of diet exposure. Results: both HFrD and HFHFrD mice exhibited marked intestinal inflammation, atrophy, and damage, alongside altered production of neutral and mixed mucins. HFD-fed mice displayed a 15-fold surge in Clostridium/Bacteroides ratio at 4 weeks. At 8 weeks, HFrD-fed mice showed a striking 10-fold rise in microbial relative abundance compared to the other diets. Both HFrD and HFHFrD triggered an early increase in Bacteroides species, but significance emerged only at 8 weeks. Conclusions: Although all obesogenic diets induced inflammation, atrophy, epithelial damage, and altered mucin patterns, HFrD and HFHFrD caused pronounced disruptions to barrier function and dysbiosis. Critically, HFD consistently raised the Firmicutes/Bacteroidetes ratio at 4 and 8 weeks, while the Clostridium/Bacteroides ratio spiked only at 4 weeks. Obesogenic diets fundamentally shifted microbial load and diversity. Therefore, bacterial ratios, such as Clostridium/Bacteroides, may signal dysbiosis and tissue damage from obesogenic diets, but further research is required for confirmation. Full article

The gut–immune–metabolic axis has emerged as a central regulator of human health, with growing evidence indicating that microbiota-derived metabolites improve gut microbial ecology, enhance intestinal barrier integrity, reduce systemic inflammation, and maintain metabolic homeostasis. This review synthesizes current mechanistic and clinical evidence on the role of postbiotics in regulating intestinal barrier integrity, immune responses, oxidative stress, and metabolic–endocrine homeostasis. The literature was identified through the PubMed/MEDLINE, Scopus, and Web of Science, integrating evidence from experimental, mechanistic, animal and clinical studies on the therapeutic potential of postbiotics to modulate the gut–immune–metabolic axis. Preclinical studies suggest that postbiotics may enhance epithelial barrier function by improving tight junction integrity through multiple pathways such as PI3K/Akt signaling, stimulating mucin-2 (MUC2) production, and reducing intestinal permeability. They modulate immune responses through interactions with Toll-like receptors, nucleotide-binding oligomerization domain receptors, and G-protein-coupled receptors (GPR41/43), influencing key signaling pathways, including NF-κB and Nrf2, and altering cytokine profiles, such as IL-10, TNF-α, and IFN-γ. Similarly, preclinical investigations have demonstrated that short-chain fatty acids (SCFAs) and other microbial metabolites may improve insulin sensitivity, regulate hepatic gluconeogenesis, stimulate glucagon-like peptide 1 (GLP-1) secretion, and modulate lipid metabolism through the FXR and TGR5 signaling pathways. Emerging human studies suggest potential benefits of postbiotics in regulating gut, immune, and metabolic health; nevertheless, clinical evidence remains limited and is influenced by variability in postbiotic composition, dosage, formulation, and metabolite profiles. Therefore, standardized production approaches and well-designed large-scale randomized clinical trials are required to confirm therapeutic efficacy and establish evidence-based applications of postbiotics. Full article

Background: The molecular changes associated with the progression of intraductal papillary mucinous neoplasm (IPMN) to pancreatic ductal adenocarcinoma (PDAC) and distant metastasis remain incompletely understood. Case Presentation: A man in his late 70s underwent pancreaticoduodenectomy and partial hepatectomy for a pancreatic head tumor with synchronous liver metastasis. Histology showed a 4.5 cm moderately differentiated PDAC arising in an IPMN with high-grade dysplasia (pT3N1M1). Genomic analysis of the IPMN, PDAC, and liver metastasis identified KRAS p.G12D, CDKN2A deletion, and GNAS p.R201H in the IPMN; additional SMAD4 p.R361C in the PDAC; and KRAS p.G12D, CDKN2A deletion, SMAD4 p.R361C, and APC p.R1450Ter in the liver metastasis. The APC alteration was confirmed by targeted sequencing and was accompanied by loss of heterozygosity at the APC locus. β-Catenin showed membranous expression in the IPMN and PDAC, but nuclear accumulation in the liver metastasis. Discussion: The shared KRAS, CDKN2A, and SMAD4 alterations support a common clonal origin of the PDAC and metastatic tumors. The absence of a detectable GNAS alteration in the liver metastasis and the presence of a metastasis-specific APC alteration are compatible with, but do not prove, branching evolution and selection of a metastatic subclone. Conclusions: This case shows a metastasis-specific heterozygous APC truncating alteration with loss of heterozygosity, accompanied by nuclear β-catenin accumulation, in an IPMN-associated PDAC. Full article

Brown mushroom stem (BMS), a nutrient-rich by-product of the mushroom processing industry, represents a potential sustainable feed ingredient for poultry. However, its effects on intestinal morphology and barrier-related gene expression in layer chicks are not well characterized. This study evaluated the influence of dietary BMS on ileal morphology and intestinal barrier-related gene expression in layer chicks. A total of 160 Lohmann LSL Lite chicks were randomly allocated to 4 dietary treatments: a control diet and control diets containing 2%, 4%, or 6% BMS as partial replacements for soybean meal on an equivalent basis, respectively. Each treatment had 5 replicates with 8 birds per replicate, and the trial lasted 36 d. Ileal samples were collected for histomorphological evaluation and quantitative real-time PCR of barrier-associated genes, including claudin-1 (CLDN1), occludin (OCLN), tight junction protein 1 (TJP1), tight junction protein 2 (TJP2), and mucin-2 (MUC2). Data were analyzed using one-way ANOVA, and orthogonal polynomial contrasts were applied to determine linear and quadratic responses to increasing BMS inclusion levels. Villus height decreased in BMS-fed groups compared with the control (linear and quadratic effects, p < 0.001), whereas crypt depth showed a quadratic response with the lowest value at 4% BMS (p < 0.001). Expression of CLDN1 mRNA was significantly elevated at 2% BMS but declined at higher inclusion levels (quadratic effect, p = 0.001). In contrast, TJP2 mRNA expression decreased with increasing BMS inclusion (linear effect, p = 0.009). No significant differences were observed for OCLN, TJP1, or MUC2 mRNA expression (p > 0.05). A composite index of barrier-related gene expression was numerically the highest at 2% BMS supplementation but did not differ significantly among treatments. These findings suggest that low dietary inclusion of BMS may support intestinal barrier-related gene expression in layer chicks, although higher levels may alter intestinal morphology without corresponding changes in barrier-related gene expression. Optimizing BMS inclusion could support sustainable poultry production by utilizing mushroom processing by-products as an alternative feed ingredient. Full article

Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is among the most clinically relevant and conceptually intricate precancerous lesions encountered in modern gastroenterology. First identified in the early 1980s as a “mucin-producing tumor,” IPMN has since undergone a profound redefinition: from an obscure and poorly classified entity to a well-established precursor of pancreatic ductal adenocarcinoma (PDAC), shaped by characteristic molecular alterations such as KRAS, GNAS, and RNF43 mutations. Over the past two decades, the reported incidence of IPMN has risen sharply, a trend largely attributable to the widespread use of high-resolution cross-sectional imaging rather than a genuine increase in disease prevalence. IPMNs are categorized anatomically into main-duct (MD-IPMN), branch-duct (BD-IPMN), and mixed-type forms and histologically into gastric, intestinal, pancreatobiliary, and oncocytic subtypes, each associated with distinct malignant potential and prognostic implications. International consensus guidelines (Sendai 2006; Fukuoka 2012; Fukuoka revision 2017; Kyoto 2024) have progressively refined strategies for risk stratification and surgical decision-making. Nevertheless, significant debate persists regarding optimal surveillance intervals, thresholds for resection, and the management of low-risk branch-duct lesions. This review offers a comprehensive and critically evaluated synthesis about IPMN, spanning its historical recognition, molecular pathogenesis, epidemiology, clinical manifestations, diagnostic evaluation, pathological features, differential diagnosis, surveillance paradigms, long-term complications, associated conditions, therapeutic options, and future directions. Particular attention is given to longstanding “myths” that have influenced clinical practice and to emerging “realities” grounded in contemporary molecular and clinical evidence. Our aim is to provide physicians with a clear and updated framework for navigating the complexities of IPMN management in current practice. Full article

Background/Objective: An obesogenic diet triggers intestinal inflammation and oxidative stress, leading to epithelial barrier dysfunction and increased risk of metabolic disorders. This study investigated the mechanisms by which quercetin protects intestinal integrity in high-fat diet (HFD)–fed mice. Methods: Mice were fed an HFD or a low-fat diet (LFD) with or without 1% quercetin, intestinal gene and protein expression, microRNA levels, permeability, and circulating intestinal biomarkers were assessed. Results: Mice fed an HFD with quercetin (HFDQ) showed a 17% improvement in intestinal barrier integrity with increased expression of tight junction and mucin genes and proteins. The nuclear translocation of the nuclear factor-κB (NF-κB) p65 subunit in the ileum decreased by 34%, whereas its acetylation was reduced by 50–57% throughout the intestine, with downregulation of NF-κB-regulated pro-inflammatory genes and proteins. Quercetin increased the nuclear factor erythroid 2-related factor 2 (NRF2) by ~ 25% across intestinal segments and upregulated antioxidant enzyme genes. It suppressed toll-like receptor 4 (TLR4) by 50% and restored AMP-activated protein kinase (AMPK) and sirtuin 1 to levels comparable to those in LFD mice. Altered microRNAs (miRNA-16, 200b, 122, 34a, and 21) supported these molecular changes. Quercetin also restored short-chain fatty acid receptors and serotonin transporters that were affected by HFD. Plasma lipopolysaccharide (LPS), cluster of differentiation 14, LPS-binding protein, and myeloperoxidase activity decreased by 36, 31, 42, and 37%, while glucagon-like peptide-1 increased by 23%. Conclusions: Quercetin protects epithelial barrier integrity against HFD-induced intestinal inflammation and oxidative stress via the AMPK-mediated NF-κB and NRF2 signaling pathways. Full article

Gemcitabine-based chemotherapy has long served as a standard treatment for urothelial carcinoma (UC), particularly in perioperative and metastatic settings. However, therapeutic efficacy is frequently limited by intrinsic or acquired resistance. Gemcitabine functions as a prodrug whose activity depends on coordinated processes involving cellular uptake, intracellular activation, metabolic inactivation, and nucleotide metabolism. Increasing evidence suggests that resistance in UC is mediated by multiple interconnected mechanisms beyond alterations in gemcitabine transport, activation, and inactivation alone. Key molecular determinants include human equilibrative nucleoside transporter 1 (hENT1), deoxycytidine kinase (dCK), cytidine deaminase (CDA), and ribonucleotide reductase regulatory subunit M1 (RRM1), which is involved in nucleotide pool maintenance and DNA synthesis. In addition, replication stress responses, apoptosis evasion pathways, and tumor microenvironment-associated factors also contribute to gemcitabine resistance. Stress-adaptive pathways involving Y-box binding protein 1 (YB-1), hypoxia-inducible factor-1 alpha (HIF-1α), and autophagy-related mechanisms may further promote survival under chemotherapy-induced stress conditions. In addition, extracellular mucin-associated mechanisms may alter intratumoral drug accessibility and contribute to resistance. In this review, we summarize UC-specific evidence regarding gemcitabine resistance and discuss how these pathways collectively shape an integrated resistant phenotype. Full article

Coordinated responses of intestinal epithelial and immune cells are essential for maintaining barrier integrity and immune homeostasis in dogs, yet our mechanistic understanding of probiotic-derived metabolites remains limited due to reliance on non-canine experimental models, highlighting the need for studies in canine-derived systems. Here, we investigated the effects of metabolites derived from Limosilactobacillus reuteri strain ATCC PTA6127 (Lr6127), delivered as a cell-free supernatant (CFS), on canine epithelial MCA-B1 cells and macrophage-like DH82 cells subjected to lipopolysaccharide (LPS)-induced inflammatory stress. Lr6127 CFS significantly reduced epithelial permeability, decreasing FITC–dextran leakage to 94.9 ± 1.9% (normalized relative to LPS-treated control, which was set as 100%) (p < 0.001), despite no detectable transcriptional changes in tight junction, adherens junction, or mucin genes. Barrier effects were instead associated with changes in markers of cellular stress responses, with heme oxygenase expression decreasing from 0.9 ± 0.1 to 0.7 ± 0.1 (p < 0.05). In DH82 immune cells, Lr6127-derived metabolites altered LPS-induced stress- and inflammation-related gene expression patterns; enhanced anti-apoptotic responses, as reflected by the increased BCL2 expression (1.4 ± 0.1 vs. 1.0 ± 0.0; p < 0.01) and elevated BCL2/BAX ratios (p < 0.01); and reduced expression of pro-inflammatory mediators including IL-6 and CCL2 (p < 0.05–0.001). Proteomic analysis corroborated that Lr6127-derived metabolites reduced the abundance of inflammatory and STAT-associated signaling proteins under LPS challenge, while indicating context-dependent changes in immune-related protein profiles under resting condition. Collectively, these results suggest that Lr6127-derived metabolites improved epithelial barrier function, which was accompanied by coordinated changes in cellular stress-related and inflammatory pathways, highlighting their potential to positively influence host responses. Full article

Background/Objectives: The microbiota–gut–brain axis (MGBA) plays a pivotal role in cognitive function, making psychobiotics a promising strategy for managing neurodegenerative diseases. Lactic acid bacteria (LAB) from traditional fermented foods represent a valuable source of candidate strains, and multi-strain consortia may offer enhanced therapeutic efficacy through synergistic effects. This study evaluated the functional and psychobiotic potential of three lactic acid bacteria (LAB) strains isolated from fermented foods, assessed as monocultures and a multi-strain consortium (MIX). Methods: The research encompassed an initial screening of the individual strains and the MIX, assessing their adhesion to mucin, stability in a static in vitro digestion model, and amino acid profiling. Subsequently, the LAB MIX underwent long-term evaluation in a dynamic gastrointestinal model (SHIME^®) inoculated with microbiota from a patient with Alzheimer’s disease, during which alterations in gut microbiota composition and amino acid metabolism were analyzed. Results: The LAB MIX demonstrated high stability under digestive stress and effective mucoadhesive properties. Furthermore, the consortium demonstrated a distinct metabolic signature, driving enhanced functional effects that complemented or exceeded those observed in individual monocultures. In the SHIME^® model, the MIX induced significant, site-specific shifts in microbial composition, notably increasing lactobacilli abundance. These taxonomic changes correlated with an enriched metabolic profile, including elevated levels of GABA precursors and amino acids with antioxidant potential, which are crucial for MGBA modulation. Conclusions: These results identify the LAB consortium as a compelling psychobiotic candidate. Further in-depth in vivo and clinical studies are required to validate its therapeutic potential for MGBA modulation. Full article

Introduction: Lung cancer, the leading cause of cancer-related mortality worldwide, is a heterogeneous malignancy comprising distinct histological and molecular subtypes, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases and adenocarcinoma (ADC) representing the most prevalent histotype. An emerging pathological feature of NSCLC, spread through air spaces (STAS)—defined as the extension of tumor cells into the lung parenchyma beyond the main tumor margin—has been associated with worse disease-free and overall survival and has been proposed as a possible predictor of recurrence to guide surgical extent. Concurrently, recent comprehensive genomic profiling of early-stage NSCLC has highlighted the need to interpret multi-omics data and their relationship with pathological variables, including IASLC histological subtypes, to better personalize treatment strategies. In this context, we investigated the overall distribution of STAS and its association with tumor mutational profiles and IASLC histological subtypes in a large real-world cohort of lung adenocarcinoma patients from the LANTERN project. Materials and Methods: In a prospective, multicenter observational study (March 2023–December 2024), 271 NSCLC patients were enrolled, and clinicopathological, immunohistochemical, and genomic data were collected; comprehensive genomic profiling was performed using the TruSight Oncology 500 assay to analyze 523 cancer-related genes, tumor mutational burden (TMB), and microsatellite instability; and STAS was assessed according to IASLC criteria. Adenocarcinoma accounted for roughly 90% of the cases, with a median age of 69 years and a predominance of stage IV disease (49.5%). STAS was evaluable in 162 cases and was detected in 17.9% of tumors. Results: STAS-positive tumors showed a higher trend towards locally advanced and advanced disease; no differences were observed in sex, age, smoking status, tumor mutational burden, or PD-L1 expression. Additionally, STAS-positive tumors showed a higher association with micropapillary, mucinous, and papillary patterns, whereas the acinar pattern was more frequent in STAS-negative tumors. The most frequently mutated genes were TP53, KRAS, EGFR, and STK11, with no significant differences between groups; ROS1 alterations were absent in STAS-negative tumors but detected more frequently in STAS-positive cases. Conclusions: Overall, these findings indicate that STAS positivity is associated with high-risk histological subtypes and advanced disease, suggesting its importance as a marker of tumor aggressiveness and emphasizing the need for its systematic evaluation in lung adenocarcinoma to better guide surgical planning and patient risk assessment. Full article

Background/Objectives: The tumour immune microenvironment (TIME) critically influences colorectal cancer (CRC) progression and therapeutic response, yet mechanisms shaping immune phenotypes remain unclear. Mucin-type O-glycosylation regulates tumour–immune interactions at the cell surface. Methods: We analysed O-glycosylation activity in 988 colorectal cancer (CRC) tumours derived from three independent cohorts: The Cancer Genome Atlas (TCGA-CRC, n = 534), the Clinical Proteomic Tumour Analysis Consortium (CPTAC2-CRC, n = 106), and the Sidra–Leiden University Medical Center (Sidra-LUMC, n = 348). O-glycosylation activity was quantified using a transcriptomic gene signature and single-sample gene set enrichment analysis (ssGSEA). Tumours were stratified into high and low O-glycosylation groups based on the median score, and associations with immune phenotypes, genomic alterations, and tumour functional states were assessed. Results: High O-glycosylation tumours exhibited an immune-desert phenotype with reduced immune-inflamed (p = 3.65 × 10⁻¹⁰) and immune-excluded (p = 0.0070) signatures alongside increased immune-desert scores (p = 0.0049) and reduced Siglec signalling (p = 8.14 × 10⁻⁵). O-glycosylation was associated with genomic stability, including lower TP53 mutation frequency (p = 0.0056), reduced aneuploidy (p = 0.0116), and decreased fraction of genome altered (p = 0.0309). High O-glycosylation tumours also showed upregulation of multidrug resistance programmes and reduced epithelial–mesenchymal transition (p = 0.0141) and proliferation (p = 0.0294). Conclusions: O-glycosylation defines a CRC subtype characterised by immune exclusion, genomic stability, and multidrug resistance, highlighting its potential as a biomarker and therapeutic target. Full article

Introduction: This study sought to explore the impact of dietary Cu deficiency on colonic health, including assessments of histopathology, barrier function, inflammatory response, and gut microbiota composition. Methods: Weaned mice were fed a copper-deficient diet for four weeks, followed by one week of intraperitoneal copper sulfate administration as a proof-of-concept rescue intervention. Colonic pathology was assessed by H&E staining, goblet cell changes by AB-PAS staining, and intestinal barrier integrity by immunofluorescence. Inflammatory cytokine levels were measured by ELISA, while protein and mRNA expression of inflammatory markers were detected by Western blot and qRT-PCR. Gut microbiota composition, diversity, and signature genus abundance were analyzed by 16S sequencing. Results: Compared to the control group, CuD mice exhibited histopathological damage in the colon, including mucosal thinning and inflammatory cell infiltration. The number of goblet cells and the expression of mucin MUC2 were significantly reduced, and the expression of tight junction proteins (ZO-1, Occludin) was downregulated, indicating impairment of both the physical and chemical intestinal barriers. Concurrently, Cu deficiency markedly elevated systemic and colonic levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and enhanced NF-κB phosphorylation. To explore potential microbial contributions to these colonic alterations, we subsequently analyzed the gut microbiota composition by 16S rRNA sequencing. This analysis revealed that Cu deficiency significantly reduced the α-diversity and species richness of the gut microbiota. This dysbiosis was characterized by a decreased abundance of beneficial bacteria (e.g., Bacteroidota, Muribaculaceae) and an increased abundance of Desulfobacterota, a pro-inflammatory taxon, as well as Akkermansia, a mucin-degrading bacterium with context-dependent effects on gut health. Intraperitoneal administration of copper sulfate (CuD + CuSO₄) partially reversed the histopathological and inflammatory changes; its effect on the gut microbiota was not assessed. Conclusions: Dietary Cu deficiency is associated with colonic injury, and these alterations were accompanied by intestinal barrier disruption, an activated inflammatory response, and gut microbiota dysbiosis. These findings provide experimental evidence highlighting the importance of copper nutrition in maintaining colonic homeostasis, though further mechanistic studies are needed to establish causal relationships. Full article