Search Results (608)

Background/Objectives: Rabbit farming in Romania is increasingly important for providing high-quality meat, yet productivity is frequently threatened by enteric diseases, particularly in young animals. Among bacterial etiologies, Clostridioides difficile (C. difficile) has emerged as a significant gastrointestinal pathogen, with findings suggestive of systemic dissemination and public health implications. This study aimed to investigate a fatal case of C. difficile infection in a farmed rabbit and to characterize the pathogen’s microbiological, toxigenic, and antimicrobial profile. Methods: An 11-month-old male German Giant Spotted rabbit presenting acute diarrhea, anorexia, and rapid deterioration after unsupervised administration of enrofloxacin and sulfaquinoxaline was submitted postmortem. Necropsy was performed, and samples from cecum, colon, liver, spleen, mesenteric lymph nodes, lungs, and femoral bone marrow were collected. Microbiological analysis included selective culture on CCFA medium, ELISA for toxin A and B detection, MALDI-TOF MS identification, PCR confirmation, and antimicrobial susceptibility testing with the VITEK 2 system. Histopathological examination was conducted on intestinal and parenchymal tissues. Results: Necropsy revealed severe congestion and necrosis of the cecal and colonic mucosa, hepatomegaly, splenic congestion, and petechial hemorrhages. C. difficile was isolated from intestinal sites, confirmed as toxigenic by ELISA and PCR. Histopathology showed necrotizing colitis with epithelial desquamation, fibrin deposition, and heterophilic infiltration. The strain exhibited resistance to clindamycin, ampicillin, and tetracycline, with susceptibility to vancomycin, linezolid, and tigecycline. Conclusions: This case demonstrates that C. difficile can cause severe disease in rabbits, particularly following antimicrobial-induced dysbiosis. The findings underscore the importance of prudent antibiotic use, monitoring of toxigenic strains in rabbit populations, and implementation of preventive strategies to mitigate health risks in both animals and potentially humans. Full article

NDRG1 protein engages with the orphan nuclear receptor NR4A1, effectively suppressing the transcriptional activity of NF-κB and influencing the inflammatory response. However, the specific roles of the NDRG family and NR4A transcription factors in inflammatory bowel disease (IBD) remain poorly defined, particularly regarding potential differential mechanisms between ulcerative colitis (UC) and Crohn’s disease (CD). We hypothesize that NDRG–NR4A interactions are differentially regulated in UC versus CD, contributing to disease-specific modulation of NF-κB signaling and inflammatory responses. Therefore, the aim was to analyze gene and protein expression of both protein families (NDRGs: NDRG1, NDRG2, NDRG3, and NDRG4; and NR4A: NR4A1, NR4A2, and NR4A3), their contributions to UC and CD, and their association with disease severity. In this cross-sectional and comparative study, we assess gene and protein expression of NR4A and NDRG1-4 in 38 UC patients, 10 CD patients, and 18 controls. Gene and protein expression levels were measured by RT-PCR (mucosa) and immunohistochemistry (colonic tissue), respectively. The colonic mucosa from remission UC patients showed upregulation of NDRG2 and the nuclear receptor genes NR4A1-3 compared with controls. NDRG4 was upregulated in active UC patients compared with controls. NDRG1 was downmodulated in active and remission UC patients compared with controls. All differences were statistically significant (p < 0.05). Decreased NR4A2 gene expression was associated with high-sensitivity C-reactive protein (p = 0.030) and erythrocyte sedimentation rate levels (p = 0.001). Our results provide the first evidence of differential alterations in the NDRG–NR4A axis in UC and CD, which could modulate NF κB signaling and the inflammatory profile differently in each disease, opening the possibility of new therapeutic options. Full article

Background: Eosinophilic infiltration is frequently observed in ulcerative colitis (UC), but its impact on disease course remains incompletely understood. This study aimed to assess eosinophilic infiltration of the colonic mucosa in patients with newly diagnosed UC and to investigate its association with the achievement of clinical remission during the first year of follow-up. Methods: A retrospective study was conducted in patients with newly diagnosed UC. Patients were stratified into two groups according to clinical outcome during the first year of follow-up: clinical remission (n = 30) and non-remission (n = 30). Clinical and laboratory data were extracted from an integrated medical information system database. Archived colonic mucosal biopsy specimens were independently evaluated by two pathologists. Mean eosinophil density across five high-power fields and peak eosinophil count were assessed. Results: In primary biopsy specimens, the median eosinophil density was 19 (11 to 27) cells in the clinical remission group and 33 (23 to 51) cells in the non-remission group. Logistic regression analysis showed that an increased eosinophil count (OR 6.48; 95% CI 1.76 to 23.88; p = 0.005) and the presence of extraintestinal manifestations (OR 5.78; 95% CI 1.17 to 28.6; p = 0.031) were associated with failure to achieve clinical remission during the first year of treatment. Conclusions: In adult patients with ulcerative colitis, a higher density of eosinophils in the colonic mucosa at the time of initial diagnosis is associated with failure to achieve clinical remission during the first year of treatment. These results should be considered hypothesis-generating and require confirmation in larger prospective studies to further clarify the potential prognostic significance of tissue eosinophilia in ulcerative colitis. Full article

The maintenance of gastrointestinal homeostasis relies on a tightly coordinated interplay between the intestinal epithelium, the immune system, and the commensal microbiome. Disruption of this balance underlies inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, and is characterized by chronic, relapsing mucosal inflammation driven by genetic susceptibility, environmental factors, immune dysregulation, and microbial imbalance. Persistent inflammation promotes repeated cycles of epithelial injury and aberrant repair, creating a permissive environment for dysplasia and the development of colitis-associated cancer, most notably colorectal carcinoma. Recent evidence identifies the anti-apoptotic regulator myeloid cell leukemia-1 (Mcl1) as a critical determinant of epithelial integrity and cellular turnover during mucosal stress. Loss or destabilization of Mcl1 disrupts epithelial homeostasis, amplifies inflammatory signaling, and accelerates tumor initiation, whereas its adaptive upregulation in established malignancy promotes tumor cell survival, metabolic fitness, and therapeutic resistance. Thus, Mcl1 functions as a context-dependent molecular switch via restraining malignant transformation during chronic inflammation while supporting tumor progression once neoplasia is established. This functional duality positions Mcl1 as both a biomarker of disease progression and a therapeutically actionable vulnerability. In this review, we synthesize recent advances elucidating how Mcl1 integrates epithelial cell-fate decisions, immune signaling and tumor evolution across the IBD–cancer continuum. We further support these concepts through integrative analyses of multiple transcriptomic datasets comparing normal colonic mucosa with colorectal tumors, and we discuss emerging pharmacological strategies targeting Mcl1 in colitis-associated cancer. Full article

Oral candidiasis (OC) is the most frequent fungal infection among users of dental prosthetic devices, immunocompromised patients, and those who underwent chemotherapy treatment and had a complication of long-term antibiotic therapy. About 150 species of Candida fungi have been described, whereas over 80% of oral fungal infections are attributed to the opportunistic pathogen Candida albicans. Pain, dryness of oral mucosa, pathological lesions, and intermittent mucosal bleeding are the main symptoms that worsen the daily functioning of the abovementioned fungal-infected patients. A promising adjunctive strategy may involve the use of probiotic bacteria to attenuate fungal colonization in the oral cavity in order to reduce the need for conventional treatment, which carries a risk of antifungal drug resistance—a significant problem worldwide. Probiotic formulations mostly incorporate commensal bacteria that naturally inhabit oral ecosystems such as Lactobacillus spp., Bifidobacterium spp., Bacillus spp., and others. Probiotic organisms may contribute to the restoration of oral microbiome homeostasis through numerous mechanisms, such as competitive control of Candida species numbers, better adhesion to oral mucosa and production of bioactive compounds and antimicrobial metabolites. Despite many studies, the current evidence base remains heterogeneous. Well-designed studies across diverse populations are required to determine whether probiotic-based interventions can be an effective and clinically useful alternative or adjunct to standard antifungal therapy of OC. Full article

Ulcerative colitis (UC) is a type of inflammatory bowel disease without curative therapeutics. Recent studies demonstrate that Akkermansia muciniphila exerts mitigating effects on UC, but the underlying mechanisms remain unclear. In this study, we isolated a strain of A. muciniphila, designated NND9, from the feces of DSS-induced ulcerative colitis model mice and investigated its effects on UC of the mouse model. NND9 significantly alleviated UC severity in the mice by restoring gut barrier integrity through improving colonic mucus layer thickness, mitigating goblet cell depletion, and halting epithelial cell death. Mechanistically, NND9 suppressed the expression of the Tnfrsf10b gene encoding death receptor 5 (DR5) on the surface of colonic epithelial cells. Additionally, NND9 inhibited the phosphorylation of kinase 3 (RIPK3) and the pseudokinase mixed-lineage kinase domain-like protein (MLKL) associated with the necrotic apoptosis pathway, thereby reducing gut epithelial cell death. NND9 also markedly ameliorated the gut microbiome of the colitis mice. Untargeted metabolomics analysis demonstrated that NND9 modulated both tryptophan and bile acid metabolism. In conclusion, NND9 exhibits curative effects on UC by resolving inflammatory reactions of the gut mucosa through the DR5-RIPK3/p-RIPK3-MLKL/p-MLKL pathway and redressing gut dysbiosis. This study provides valuable information for the development of innovative therapeutic strategies for the treatment of UC. Full article

Pertussis is a highly contagious respiratory infection caused by Bordetella pertussis and remains a persistent global health challenge despite widespread vaccination. This review aims to analyze the immune pathogenesis of B. pertussis infection and to identify key immunological limitations of current acellular pertussis vaccines that contribute to ongoing transmission. A narrative review of the literature was conducted, focusing on mechanisms of host–pathogen interaction, immune evasion, and vaccine-induced immunity. Evidence indicates that although acellular vaccines effectively reduce disease severity, they fail to prevent nasopharyngeal colonization and transmission, largely due to insufficient induction of mucosal immunity, T helper 1 (Th1) and T helper 17 (Th17) responses, and airway tissue-resident memory T cells. In contrast, natural infection induces broader immune responses, including secretory IgA production and robust cellular immunity, which are associated with improved bacterial clearance. Emerging next-generation vaccine strategies, including mucosal, outer membrane vesicle-based, and live-attenuated platforms, demonstrate enhanced ability to reduce bacterial colonization in preclinical and clinical models. In conclusion, effective control of pertussis transmission will require vaccine approaches that replicate infection-induced immunity at the respiratory mucosa, emphasizing the need for redesigned immunization strategies. Full article

This study aimed to investigate the effects of pterostilbene (PTE) on the intestinal barrier function, antioxidant capacity, lipid metabolism, and microbial and metabolite homeostasis of suckling piglets via its action on breast milk. Findings indicate that PTE supplementation enhanced the antioxidant status of mature milk and strengthened intestinal barrier function in piglets. Specifically, PTE enhanced intestinal antioxidant status and fatty acid β-oxidation in piglets by regulating the PI3K-AKT and SIRT1-Nrf2/Keap1 signaling pathways. 16S rDNA sequencing and Liquid Chromatography–Mass Spectroscopy (LC–MS) identified breast milk and gut microbiota and their metabolites, respectively. Results indicate that PTE significantly elevated levels of amino acid derivatives in colostrum (Glutathione Reducedform (GSH) and N-acetyl-L-glutamate (NAG)), whilst concurrently reducing levels of glycerophospholipid-related metabolites in both colostrum and mature milk (p < 0.05). Moreover, PTE supplementation markedly altered the composition of the colonic mucosal microbiota in piglets, with Faecalibacterium, Mucispirillum and Ruminococcus identified as key beneficial microbial markers of the colonic mucosa. Combined multi-omics revealed strong correlations in microbial community composition between mature milk and the colon, identifying glycerophospholipid metabolism as a key metabolic pathway that may be associated with the regulatory effects of PTE on milk and the piglet colon. In conclusion, the PTE supplement can improve the quality of breast milk and have a positive impact on the intestinal homeostasis of the offspring. Full article

The intestinal mucosal barrier is a layered structure comprising fundamental components that play important roles in regulating paracellular permeability. Disruption of intestinal barrier homeostasis predisposes to infections, mucosal damage, and metabolic and allergic diseases. To provide protection against potential damage to the intestinal mucosa, agents such as prebiotics and probiotics are recommended due to their ability to secrete components and metabolites (e.g., bacteriocins, organic acids, enzymes) that can exert beneficial biological effects. The aim of this study is to comprehensively investigate the effects of a postbiotic derived from Pediococcus acidilactici on healthy rat intestinal tissue. A total of 78 Wistar Albino rats were used in this study. Following compositional analysis of the postbiotic, the animals were administered the postbiotic orally via gavage for different durations (7, 14, 21, 28 days) and at different doses (250 mg/Kg, 500 mg/Kg, 1000 mg/Kg). Characterization of the produced postbiotic revealed a diverse spectrum of biologically active compounds, including organic acids, phenolics, and volatile compounds. Histopathological examination of intestinal sections (duodenum, jejunum, ileum, cecum, colon, and rectum) showed no pathological lesions in any of the experimental groups. Conversely, immunohistochemical analysis revealed that the postbiotic increased the expression of CLDN3, OCLN, ZO1, AQP4, and AQP8, proteins involved in intestinal permeability and fluid transport, in a dose-dependent manner. These results highlight the potential of Pediococcus acidilactici as a supportive agent in a range of intestinal pathologies, including major intestinal diseases such as Crohn’s disease, ulcerative colitis, and inflammatory bowel disease (IBD). Full article

Growing evidence suggests that chronic kidney disease (CKD) profoundly disrupts gut microbiome and its activity. This study explores how CKD affects colon microbial metabolism, focusing on (1) the representativeness of fecal metabolomics, (2) saccharolytic and proteolytic fermentation metabolites, and (3) the gut microbiome’s role in the partitioning of tryptophan in its metabolic pathways. Tryptophan’s main metabolic pathways include the indolic and the kynurenine pathways, which lead, respectively, to the formation of indoxyl sulfate and kynurenine, both contributing to uremic toxicity. Using a rat model of CKD, we evaluated whether fecal concentrations of microbial compounds, on which most studies are based, reflect the colonic concentrations in contact with the gut mucosa. Thus, we quantified the concentration and content of amino acids, indole, p-cresol, and also short-chain fatty acids, in different colon sections. We demonstrated that CKD promotes increased proteolytic fermentation and an augmented tryptophan partitioning into both the indolic and kynurenine pathways. Depletion of the indolic pathway obtained upon antibiotic treatment leads to a further enhancement of the kynurenine pathway. Full article

Background/Objectives: Enteric glial cells (EGCs) are key players in regulating enteric neurons and gastrointestinal functions including disturbed gut motility in diabetic patients. Enteric neuronal damage has been shown in type 1 diabetes, but EGCs’ vulnerability to hyperglycaemic insults requires more investigation. Therefore, we aimed to study the quantitative changes in the EGC network enmeshing enteric plexuses, intestinal smooth muscle and mucosa in streptozotocin-induced acute (1-week) and chronic (10-weeks) diabetic rat models. Methods: Fluorescent immunohistochemistry using Sox10 glial and HuC/HuD pan-neuronal markers, immunogold electron microscopy and ELISA were performed on different gut segments. Results: In the submucosal ganglia of the ileum and colon, the density of Sox10-immunoreactive EGCs was significantly reduced in acute and increased in chronic hyperglycaemic rats without any changes in the duodenum. In the myenteric ganglia, regionally distinct alterations of glial density were noted in acute hyperglycaemia; however, a remarkable decrease was observed in chronic animals. Alterations of neuronal density did not follow the pattern of glial changes, resulting in shifts in the glia/neuron ratio. The presence of Sox10-HuC/HuD-immunoreactive cells and their diabetes-related quantitative changes were also revealed in enteric plexuses. The density of Sox10-labelling gold particles was significantly increased in the duodenal myenteric glia of diabetic rats. Muscular EGC density increased only in the colon after acute hyperglycaemia and changed in all segments after chronic hyperglycaemia. Glial fibrillary acidic protein levels decreased in the small intestine of chronic hyperglycaemic rats. Conclusions: Our present findings reveal time-dependent and regionally distinct changes in the EGC network in response to hyperglycaemia, contributing to diabetic enteric neuropathy and gut motility disturbances. Full article

Zearalenone (ZEN) is a widely distributed estrogenic mycotoxin that compromises intestinal health in pigs, but its spatial difference ZEN and niche-specific regulatory effects on the intestinal microbiota remain largely unelucidated. In this study, 12 healthy three-way crossbred weaned piglets (Duroc × Landrace × Yorkshire) were randomly divided into two treatments. The control group (CON) was fed with the basal diet, and the treatment group (ZEN) was supplemented with 1.5 mg ZEA/kg of the basal diet for 28 days. Chyme and mucosal microorganisms in the duodenum, jejunum, ileum, colon and cecum were profiled by using 16S rDNA sequencing. The results indicated that ZEN significantly reduced the α-diversity of ileal chyme, while the abnormal increase in α-diversity of ileal and cecal mucosa represented a pathological signature of intestinal mucosal barrier damage induced by ZEN, which was detrimental to intestinal health. β-Diversity analysis revealed ZEN altered the microbial community composition of the cecal chyme. LEfSe analysis revealed gut segment-specific and niche-specific biomarker taxa among the groups, and functional prediction further indicated that ZEN exposure significantly perturbed key metabolic pathways: it downregulated nicotinate and nicotinamide metabolism as well as the citrate cycle in ileal chyme and upregulated the pentose and glucuronate interconversions pathway in cecal chyme. Collectively, this study demonstrated the effects of ZEN on the intestinal microbiota across spatial difference and ecological niches in weaned piglets, providing a basis for elucidating the microecological mechanisms underlying ZEN-induced intestinal injury in pigs. Full article

Background/Objectives: Dietary intake of fruits and vegetables (FVs) has been inversely associated with a lower risk of ulcerative colitis. Using a pig model, we evaluated the effect of FV supplementation on dextran sulfate sodium (DSS)-induced colitis. Methods: Six-week-old pigs were fed a grower diet (negative control), grower diet + 4% DSS (positive control), half-FV diet + DSS, or full-FV diet + DSS. FV levels matched half or full daily recommendations from the Dietary Guidelines for Americans (DGA). Clinical signs were monitored; proximal colon contents (PCs) and mucosa (PCM) were analyzed for metagenome, transcriptome and histopathology. Results: Full-FV pigs showed no diarrhea, less fecal occult blood (FOB), crypt hyperplasia, but no changes in gene expression or microbiome diversity (p < 0.05). Half-FV pigs had increased FOB, differentially expressed genes (DEGs) linked to tissue remodeling, crypt/goblet cell hyperplasia and two cases of diarrhea (p < 0.05). DSS controls showed reduced immune-related DEGs, altered microbiome, PCM erosion, FOB, and persistent diarrhea in one pig (p < 0.05). Conclusions: A three-week full-FV diet conferred protection against DSS-induced colitis, with a dose-dependent protection of intestinal tissue and gut metagenome under inflammatory challenge. Full article

Foreign material is an uncommon finding in routine gastrointestinal histopathology, but may occasionally contribute to disease pathogenesis or create diagnostic pitfalls. We report two illustrative cases highlighting the diverse clinical and histologic implications of ingested plant material. The first case involves a 10-year-old boy who presented with clinical features consistent with acute appendicitis and underwent appendectomy. Although gross examination revealed a macroscopically unremarkable appendix, histological evaluation demonstrated mucosal ulceration associated with an impacted plant seed within the appendiceal lumen, supporting a diagnosis of obstructive acute appendicitis. The second case describes a 60-year-old woman undergoing a screening colonoscopy, during which a small sessile lesion in the transverse colon was resected. Histologic examination revealed no colonic mucosa; instead, the specimen consisted entirely of plant material, morphologically consistent with a tomato seed, representing an incidental finding mimicking a colonic polyp. These cases underscore that plant seeds, while rare, may act as obstructive agents in appendicitis or simulate true pathological lesions during endoscopic and histologic evaluation. Awareness of the characteristic microscopic features of plant material is essential to avoid misdiagnosis and to recognise their potential clinical and forensic relevance. Full article

Background/Aim: Fermented soybean-based products are known to influence gut microbial composition; however, the long-term effects of multicomponent soybean fermented preparations on gut microbiota and colonic mucosal features remain insufficiently characterized. This study examined the effects of a commercially available soybean fermented preparation (SFP), containing additional fermented plant and marine derived components, on gut microbial community structure and colonic histological features in BALB/c mice. Methods: BALB/c mice received oral SFP (1000 mg/kg) for 30 and 60 days. Gut microbial communities were analyzed using full-length rRNA operon sequencing. Colonic mucosal architecture and goblet cell density were evaluated via histological analysis (H&E). Results: SFP supplementation induced significant β-diversity separation at both 30 and 60 days (p < 0.05), indicating consistent restructuring of the gut microbial community. While alpha diversity (Observed OTUs) remained stable at 30 days, Shannon and Simpson indices were significantly reduced at 60 days (p = 0.001), indicating reduced community evenness driven by increased dominance of specific taxa, including Duncaniella. At the genus level, SFP administration was associated with increased relative abundances of Akkermansia, Lactobacillus, and Duncaniella, accompanied by reductions in several genera previously linked to dysbiosis. Histological analysis demonstrated a significant increase in goblet cell density (p < 0.01) in SFP-treated mice. Conclusions: Long-term SFP supplementation was associated with sustained alterations in gut microbial composition and measurable histological changes in the colonic mucosa. While these findings indicate that SFP intake influences microbial structure and goblet cell abundance, further studies are required to determine the functional and physiological implications of these changes, particularly in relation to epithelial barrier function and host health. Full article