Search Results (623)

Early weaning in intensive lamb production improves reproductive efficiency but predisposes lambs to diarrhea, oxidative stress, and intestinal barrier dysfunction, highlighting the need for non-antibiotic strategies to protect gut health. This study evaluated whether a sheep-derived mixed probiotic could alleviate early weaning–induced intestinal injury and clarified its potential molecular mechanisms. Early weaning reduced body weight, average daily gain and feed efficiency, increased diarrhea, decreased plasma and colonic catalase (CAT), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) activities, increased malondialdehyde (MDA), elevated interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), reduced interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), increased plasma and mucosal immunoglobulin A, M, and G (IgA, IgM, IgG), and increased colonic lipopolysaccharide (LPS) with reduced diamine oxidase (DAO). Intestinally, EW induced villus atrophy, deeper crypts, lower villus height-to-crypt depth ratios, goblet cell loss, higher histopathological scores, and decreased colonic mucin 2, zonula occludens-1, claudin-1, and occludin. Probiotic supplementation partially reversed these alterations, restoring antioxidant enzyme activities, improving villus architecture and barrier protein expression, and rebalancing cytokine and immunoglobulin profiles. Transcriptomic and network analyses showed that early weaning activated Cytokine–cytokine receptor, NF-κB, TNF and Th17 pathways, whereas probiotics suppressed a weaning-responsive inflammatory gene module, downregulated key hub genes, and enhanced peroxisome proliferator-activated receptor (PPAR) signaling. These results show that supplementing early-weaned lambs with a mixed probiotic generated from sheep is an efficient nutritional strategy to reduce intestinal oxidative and inflammatory damage associated with weaning and to enhance their health and performance. Full article

Celiac disease (CeD) is a chronic immune-mediated enteropathy triggered by dietary gluten in genetically predisposed individuals which also entails intestinal dysbiosis. This hallmark microbial imbalance provides a rationale for exploring interventions that could modulate the gut ecosystem. Cocoa is a bioactive food rich in polyphenols, theobromine, and fiber, compounds known to have an influence on both immune function and gut microbiota composition. Here, we investigated the effects of cocoa supplementation on the gut microbial profile and predicted functionality in DQ8-D^d-villin-IL-15tg mice, genetically predisposed to CeD. Animals were assigned to a reference group receiving a gluten-free diet (GFD), a gluten-containing diet group (GLI), or the latter supplemented with defatted cocoa (GLI + COCOA) for 25 days. The cecal microbiota was analyzed via 16S rRNA sequencing, and functional pathways were inferred using PICRUSt2. Goblet cell counts and CeD-relevant autoantibodies were measured and correlated with microbial taxa. Cocoa supplementation partially attenuated gluten-induced dysbiosis, preserving beneficial taxa such as Akkermansia muciniphila and Lactobacillus species while reducing opportunistic and pro-inflammatory bacteria. Functional predictions suggested differences in the predicted microbial metabolic potential related to amino acid, vitamin, and phenolic compound metabolism. Cocoa also mitigated goblet cell loss and was inversely associated with anti-gliadin IgA levels. These findings suggest that cocoa, as an adjuvant to a GFD, could be of help in maintaining microbial homeostasis and intestinal health in CeD, supporting further studies to assess its translational potential. Full article

Lipopolysaccharide (LPS) is widely used to model immune stress in weaned piglets, but it does not fully replicate the pathophysiological alterations induced by live bacterial infection. This study therefore established an oral Salmonella enterica (SE) challenge model and systematically compared its effects with those of LPS to evaluate its potential as a complementary immune stress paradigm. Forty piglets were assigned to five groups: control (saline), LPS (intraperitoneal, 100 μg/kg BW), and three SE groups receiving low-, middle-, or high-dose oral SE (1 × 10⁸ CFU/mL, 2 × 10⁸ CFU/mL, or 3 × 10⁸ CFU/mL in a 10 mL saline volume, respectively). Both LPS and SE significantly reduced average daily gain, while only SE challenge decreased colon length. A transient rectal temperature elevation occurred at 8 h in all challenged groups, persisting at 12 h in the LPS and high-dose SE groups. Serum cytokine analysis revealed that LPS induced early but transient interleukin-12 and tumor necrosis factor-α elevation at 8 h, followed by sustained suppression of interferon-γ, interleukin-6, and interleukin-8. In contrast, the middle-dose SE triggered robust increases in multiple pro-inflammatory cytokines at 24 h. Both challenges significantly reduced the CD4⁺/CD8⁺ T cell ratios in blood and lymphoid organs and decreased intestinal interleukin-10 levels. SE infection produced more severe intestinal pathology, including dose-dependent villus perforations, microvillus disorganization, and mitochondrial cristae vacuolization, beyond the villus shortening and goblet cell reduction observed in both groups. While both LPS and SE induced immune stress and intestinal injury, SE infection caused more severe and comprehensive pathophysiological alterations. Oral administration of 2 × 10⁹ CFU SE for 24 h established a physiologically relevant immune stress model that effectively mimics natural Salmonella infection in weaned piglets, providing a valuable tool for studying enteric diseases and evaluating interventions. Full article

Since there is currently no cure for Parkinson’s disease, pharmacobiotic approaches based on gut microbiota—capable of producing pharmacologically active compounds—are under development. In this study, we propose LfU21, derived from the strain Limosilactobacillus fermentum U-21, as a candidate pharmacobiotic. To evaluate its efficacy, a combined LPS- and lactacystin (LAC)-induced Parkinson’s disease model was established in Wistar rats. Effects were assessed using behavioral, biochemical, immunomodulatory, and transcriptomic biomarkers. LfU21 administration reduced α-synuclein levels, altered motor performance in the “Rung ladder” test, and modulated bdnf gene expression in the right and left striata. Under LPS exposure, LfU21 prevented alterations in immune response markers, GSH levels, drd2 and bdnf gene expression, and intestinal goblet cell counts. In LAC and LAC + LPS groups, LfU21 mitigated the rise in α-synuclein, the decline in bdnf expression, and behavioral deficits in the “Open Field” and “Rung ladder” tests, respectively. The multifunctional activity of LfU21 in a combined Parkinson’s disease model underscores its therapeutic potential and helps identify a target patient cohort for future clinical trials. Full article

Background/Objectives: Impaired intestinal barrier function is a hallmark of inflammatory bowel disease (IBD). Akkermansia muciniphila and its outer membrane protein Amuc_1100 can enhance this barrier, but the clinical application of Amuc_1100 is limited by the fastidious growth of its native host. This study aimed to overcome this by utilizing the robust probiotic Lacticaseibacillus paracasei L9 for targeted Amuc_1100 delivery. Methods: We engineered Lc. paracasei L9 to express Amuc_1100 via intracellular (pA-L9), secretory (pUA-L9), and surface-display (pUPA-L9) strategies. Their efficacy was assessed in Lipopolysaccharide (LPS)-induced macrophages and a dextran sulfate sodium (DSS)-induced colitis mouse model, evaluating inflammation, barrier integrity, and mucosal repair. Results: The secretory (pUA-L9) and surface-display (pUPA-L9) strains most effectively suppressed pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in macrophages. In mice, both strains alleviated colitis and outperformed native A. muciniphila in improving disease activity. Crucially, they exhibited distinct, specialized functions: pUA-L9 acted as a systemic immunomodulator, reducing pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α), elevating anti-inflammatory mediators (IL-4 and IL-10), and promoting goblet cell differentiation; notably, the inhibitory effect of pUA-L9 on IL-6 expression was approximately 2-fold greater than that of pUPA-L9. In contrast, pUPA-L9 excelled in local barrier repair, uniquely restoring mucus layer integrity (Muc1, Muc2, and Tff3) and reinforcing tight junctions (ZO-1, Occludin, Claudin1, Claudin3, and Claudin4). In particular, pUPA-L9 increased Muc2 expression by approximately 3.6-fold compared with pUA-L9. Conclusions: We demonstrate that the subcellular localization of Amuc_1100 within an engineered probiotic dictates its therapeutic mode of action. The complementary effects of secretory and surface-displayed Amuc_1100 offer a novel, spatially targeted strategy for precision microbiome therapy in IBD. Full article

Background/Objectives: Appendiceal collision tumors (ACTs), defined by the coexistence of two or more histologically distinct neoplastic components within the appendix, are rare entities. We aimed to characterize their clinicopathologic features, management strategies, and outcomes by integrating an institutional case series with a systematic review of the literature. Methods: We retrospectively identified ACTs diagnosed at our institution and performed a PRISMA 2020-guided search of PubMed, Scopus, and Web of Science databases through May 2025 for case reports and case series. Two reviewers screened studies and extracted data on presentation, histologic composition, treatment, approaches and outcomes. Results: ACTs accounted for 4% of appendiceal tumors in our institution, all combining a neuroendocrine neoplasm (NEN) with a low-grade appendiceal mucinous neoplasm. The literature search identified 69 ACTs from 33 studies; pooled with our cases, 74 patients were evaluated. The most common pairings were NEN–appendiceal mucinous neoplasm (53%) and NEN–adenocarcinoma (26%), while three-component tumors were rare (n = 2). Early-stage tumors (pTis–pT1) were uniformly managed with appendectomy or limited resection, in line with established stage-based management algorithms for appendiceal neoplasms. Advanced-stage tumors (pT3–pT4) were treated according to the biologically dominant component, frequently with colectomy and, in high-risk mucinous disease, cytoreductive approaches. Across stages, outcomes appeared to be driven by the non-neuroendocrine component; a coexisting low-grade NEN did not independently confer worse prognosis. In ACTs with an adenocarcinoma component, goblet cell morphology was common, and outcomes appeared similar to those reported for non-collision appendiceal adenocarcinoma. Conclusions: ACTs represent a heterogeneous group in which prognosis is dictated by the non-neuroendocrine component and tumor stage. Low-grade NEN components appear biologically indolent, whereas adenocarcinoma and high-risk mucinous components have been observed to exhibit behavior similar to their solitary counterparts. Full article

Background: Amoxicillin, clindamycin and azithromycin are the most frequently prescribed antibiotics for odontogenic infections, but their comparative effects on gut microbiota and intestinal homeostasis remain insufficiently understood. Disruption of gut microbiota, short-chain fatty acid (SCFA) production, and mucosal barrier integrity may contribute to gastrointestinal symptoms. We aimed to compare the impacts of these antibiotics on gut microbiota, SCFA levels, and colonic goblet cells. Methods: C57BL/6N mice were treated with oral amoxicillin, clindamycin, or azithromycin at clinically relevant dosages. Cecal index, fecal water content, and diarrhea index were assessed during treatment and recovery. Gut microbiota composition and absolute bacterial abundance were determined using 16S rRNA amplicon absolute quantification sequencing. SCFAs in cecal contents were quantified by gas chromatography–mass spectrometry. Goblet cell abundance and Muc2 mRNA expression in colon tissues were evaluated using Alcian blue staining and RT-PCR. Results: Amoxicillin caused moderate increases in cecal index, reduced Ligilactobacillus abundance, increased Escherichia-Shigella, lowered SCFA levels, and decreased goblet cells and Muc2 expression, with partial recovery after two weeks. Clindamycin induced more severe dysbiosis, including sustained Proteobacteria expansion, persistent loss of beneficial taxa, 86–90% reduction in SCFA production, and lasting decreases in goblet cells and Muc2 expression without recovery during the observation period. Azithromycin caused mild and reversible changes across all parameters. Conclusions: Among the three antibiotics, azithromycin had the least detrimental effects on gut microbiota, SCFA production, and mucosal barrier function, whereas clindamycin caused profound and persistent intestinal disruption. These findings provide comparative evidence to inform antibiotic selection in clinical practices. Full article

This study examined the effects of dietary aniseed, thyme, and basil essential oils (EOs) on growth, health, and tissue integrity of common carp (Cyprinus carpio) reared in a recirculating aquaculture system (RAS). Juvenile carp (102 ± 2.8 g) were fed for 12 weeks four isonitrogenous diets: a control and three diets supplemented with 0.2% aniseed (V1), thyme (V2), or basil (V3) oils. Growth performance was not significantly affected (p > 0.05). Flesh biochemical composition improved, with higher protein in V1 (17.85 ± 0.22%) and lower fat in V3 (1.78 ± 0.21%) compared to the control. Hematological parameters and antioxidant enzymes (SOD, CAT, GPx) indicated enhanced immune and oxidative status, while MDA (malondialdehyde) levels decreased. SOD activity increased in treated groups, reaching 4.329 U mg⁻¹ protein in muscle and 4.908 U mg⁻¹ protein in liver in V2, compared to 2.775–3.677 U mg⁻¹ protein (muscle) and 3.508–4.349 U mg⁻¹ protein (liver) in controls. CAT activity was highest in the same group 57.045 U mg⁻¹ protein versus 31.403 U mg⁻¹ protein in controls. Microbiological assessment revealed reduced total aerobic bacteria and Enterobacteriaceae counts in EO-fed fish. Histological analysis showed healthier hepatic and intestinal structures, reduced vacuolation, intact epithelium, and abundant goblet cells in EO-treated groups. Full article

Eurotium cristatum-Fermented White Tea (FWT) significantly alters white tea (WT) composition, increasing caffeine while decreasing polyphenols and amino acids. FWT effectively ameliorated dextran sulfate sodium (DSS)-induced murine colitis symptoms (reducing weight loss, colon shortening). Mechanistically, FWT suppressed TLR4/Myd88/NF-κB signaling and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) while upregulating tight junction proteins (ZO-1, occludin, claudin-1), MUC2, and E-cadherin. Single-cell/spatial transcriptomics revealed that FWT treatments augment enterocyte, goblet cell, and stem cell populations, optimize goblet function, restructure stem cell differentiation, and induce epithelial REG3B (antimicrobial) and LYPD8 (motility inhibitor), plus immunomodulator GM42418 lncRNA across cell types, repairing the barrier. FWT intervention was also associated with an increase in beneficial bacteria (Akkermansia, Lactobacillus, Bifidobacterium), restoration of microbiota balance, and elevated levels of short-chain fatty acids (SCFAs) and was associated with alterations in caffeine-related metabolite profiles. Collectively, these multi-scale changes correlate with the alleviation of UC, suggesting an integrated mechanism involving mucosal barrier repair, immune–stromal modulation, microbiota–metabolism regulation, and cellular reprogramming. Full article

Goose astrovirus 2 (GAstV-2) infection leads to visceral gout and swollen kidneys in goslings, causing a 5–50% mortality rate and significant economic losses for goose flocks. While most studies on the virus’s pathological damage have focused on the kidneys, few reports have examined the effects of this fecal-oral pathogen on the digestive system. This study investigated GAstV-2 localization, cellular targets, and its impact on intestinal structure and homeostasis in orally infected goslings. Twenty 1-day-old goslings were randomly assigned to the infected and control groups. Clinical signs, organ lesions, viral distribution, histopathology, and alterations in intestinal cell populations, cytokine expression, and signaling pathways were assessed at 7 days post-infection. GAstV-2 was detected in the duodenum, jejunum, ileum, cecum, and rectum, with the highest viral load in duodenal crypt cells. Infection induced crypt cell necrosis, reduced villus height, decreased villus-to-crypt ratio, and lowered numbers of goblet cells and Lgr5+ intestinal stem cells. In contrast, Paneth cell abundance, Bmi1+ stem cells, and tight junction-related gene expression increased. Inhibition of stem cell differentiation into goblet cells was observed, mediated by modulation of the Notch signaling pathway. Proinflammatory cytokines, including IL-1β, IL-6, IL-8, IL-22, and TNF-α, were markedly upregulated, indicating a strong inflammatory response. These results demonstrate that GAstV-2 preferentially targets duodenal crypt cells, disrupts epithelial renewal, and impairs mucosal barrier function, while triggering compensatory regenerative and immune mechanisms. This study provides new insights into the intestinal pathogenesis of GAstV-2 and identifies potential targets for interventions to mitigate intestinal injury and economic losses in gosling production. Full article

Prolonged periods of sailing may contribute to the development of functional constipation, which can significantly impair an individual’s work efficiency. Currently, the efficacy of Bifidobacteria in treating functional constipation is gaining recognition. However, since the therapeutic effects of Bifidobacteria are strain-specific, further research is required on strains isolated from pre-voyage fecal samples. This study examines the role of gut microbiota in post-stroke constipation, aiming to identify specific microbial biomarkers for the development of targeted therapeutic strategies. B. adolescentis was identified through metagenomic analysis and subsequently isolated for validation. In the experimental group (EG), C57BL/6J mice received fecal suspension treatment following a 12-day navigation period, which was subsequently followed by a 12-day oral administration of B. adolescentis. After treatment, EG significantly improved fecal volume, intestinal motility, and goblet cells; reversed microbial ecological imbalance; reduced pathogens (E. coli and Klebsiella) by restoring arginine/bile acid metabolism, decreasing Tauro-ursodeoxycholic acid (TUDCA) content, 5-Hydroxytryptamine 4 Receptor (5-HT4R)/Slc8a1 signaling, and Ca²⁺ signaling pathway; and restoring beneficial species (B. adolescentis, Pseudomonas aeruginosa). This study provides new insights into probiotics in improving human intestinal health. Full article

We investigated the roles and regulation of contractile and sodium ion transporter proteins in the pathogenesis of diarrhea in the acute ulcerative colitis. Acute ulcerative colitis was induced in male Sprague-Dawley rats using dextran sulfate sodium (DSS) in drinking water for seven days. The effects of nobiletin, a citrus flavonoid, were also examined. Increased myeloperoxidase activity, colon mass, and inflammatory cell infiltration were associated with damage to goblet cells and the epithelial cell lining indicating the development of acute ulcerative colitis. SERCA-2 calcium pump expression remained unchanged, whereas the phospholamban (PLN) regulatory peptide was reduced and its phosphorylated form (PLN-P) increased, suggesting a post-translational increase in SERCA-2 activity in the inflamed colon. Higher levels of IP3 were associated with a decrease in the Gαq protein levels without altering phospholipase C expression, suggesting that IP3 regulation is independent of Gαq protein signaling. In addition, the expression of sodium/hydrogen exchanger isoforms NHE-1, NHE-3 and carbonic anhydrase-1 and sodium pump activity were decreased in the inflamed colon. Nobiletin treatment of colitis selectively reversed the inflammatory and oxidative stress markers, including superoxide dismutase and catalase without restoring the expression of ion transporters. This study highlights alterations in the expression of ion transporters and their regulatory proteins in acute ulcerative colitis. These changes in the ion transporters are likely to reduce NaCl absorption and alter contractility, thereby contributing to the pathogenesis of diarrhea in the present model of acute ulcerative colitis. Nobiletin selectively ameliorates acute colitis in this model. Full article

Background: Intestinal-type vulvar adenocarcinoma (VAIt) is an exceptionally rare form of primary vulvar cancer, characterized by histological features resembling mucinous colonic carcinomas, including villo-glandular structures composed of goblet and Paneth cells with intracytoplasmic mucin. Objective: To provide a comprehensive synthesis of the existing literature on VAIt and to also report a case from our institution in order to define its clinical, pathological, and immunohistochemical characteristics and its management and prognosis. Materials and Methods: A systematic review of the literature according to PRISMA guidelines was performed through searching five electronic databases (MEDLINE, EMBASE, Web of Science, SCOPUS and Cochrane Library), considering studies from 1998 to May 2025. In our research, we included all peer-reviewed studies which reported cases of VAIt. Data about VAIt were extracted by included studies and compared. Results: All in all, 32 studies with a total of 40 cases (including our case) of VAIt were assessed. The median age at diagnosis was 58 years. Most tumors arose in the labia or perineal structures, often mimicking benign lesions. Immunohistochemistry consistently showed CK20 and CDX2 positivity, with variable CK7 and p16 expression. FIGO stage IA was the most frequent stage at diagnosis. Surgical excision was the mainstay of treatment, while adjuvant therapy was less commonly reported. Lymph node metastases were present in about 31.5% of cases. Despite aggressive histology, most patients were disease-free at follow-up. Mortality due to disease occurred in 10% of cases. Conclusions: VAIt is a very rare histotype of vulvar cancer. Compared to vulvar squamous cell carcinomas, approximately 40% of early-stage clinical diseases reported in the literature presented positive inguinal lymph nodes with recurrence even after many years. The optimal treatment is not well defined and should be based on the individual clinical history of the patient, as there are no established guidelines. Further studies and longer follow-up periods are needed to clarify the best therapeutic management and its long-term prognosis. Full article

As a nutritionally important amino acid, cysteine (Cys) could attenuate oxidative damage on growth performance and intestinal barrier function in piglets. However, the mechanism of Cys in attenuating intestinal injury remains unclear. The aim of this study was to investigate the mechanism of Cys in defending against intestinal inflammation in piglets. A total of twenty-four piglets were divided into four groups and fed a diet with or without 0.1% BPA or Cys for a 28 d feeding trial. The results showed that Cys supplementation reinstated the jejunal barrier by increasing cell proliferation and the goblet cell number, and decreased cell apoptosis upon BPA exposure. Cys supplementation also decreased serum and jejunal pro-inflammatory cytokine and immunoglobulin levels in BPA-challenged piglets. Furthermore, Cys mitigated inflammation by normalizing the activation of the toll-like receptor 4 (TLR4)-JNK/MAPK-nuclear factor-kappa B (NF-κB) pathway caused by BPA. Additionally, dietary Cys supplementation restored the levels of butyrate, valerate and isovalerate in cecum contents that were decreased by BPA exposure. Meanwhile, Cys supplementation normalized the abundances of Prevotellaceae and Romboutsia upon BPA exposure. In conclusion, Cys is critical to nutrition through attenuating intestinal inflammation by regulating gut microbial balance and suppressing the TLR4-JNK/MAPK-NF-κB pathway. Full article

Dry Anophthalmic Socket Syndrome (DASS) is a multifactorial condition that affects roughly half of all prosthetic eye wearers and remains frequently underrecognized. It is characterised by symptoms such as dryness, discomfort, discharge, and inflammation of the socket surface. Diagnostic criteria include validated symptom questionnaires (e.g., OSDI, DEQ-5, SANDE) and at least one clinical sign such as conjunctival staining, blepharitis, or reduced tear meniscus height. This review describes the anatomical, cellular, and molecular changes associated with DASS. Meibomian gland dysfunction is common, with a significant reduction in gland density and structure. Goblet cell density is also often decreased, particularly in the tarsal and bulbar conjunctiva, although findings may be affected by topical treatments. Increased conjunctival inflammation—evidenced by immune cell infiltration and elevated markers such as MMP-9 and ICAM-1—is frequently observed, particularly in the posterior socket lining. Oxidative stress, mediated by dysregulated NOX4, KEAP1, and NRF2 expression, appears to play a contributory role. Additional factors influencing DASS include eyelid malpositions such as entropion and ectropion, prosthesis smoothness and amount of tear film production. Poor hygiene practices and environmental factors may exacerbate symptoms. Given its multifactorial aetiology, DASS requires a complex management strategy targeting inflammation, tear film instability, mechanical irritation, eyelid position and patient education. Increased awareness, standardised diagnostics, and evidence-based care protocols are critical to improving outcomes for prosthetic eye wearers. Full article