Probiotics and Antimicrobial Proteins最新文献

Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea and colitis, driven by toxin-mediated epithelial injury and inflammation. While antibiotics such as vancomycin remain the primary treatment, they can further disrupt the gut microbiota and promote recurrence. Probiotics, including yeast strains, have emerged as potential adjunctive therapies for mitigating CDI. In this study, several Saccharomyces cerevisiae strains were evaluated for their probiotic potential, and strain 48338 was identified as the most promising candidate based on its gastrointestinal tolerance, auto-aggregation ability, and antioxidant activity. Using a CDI mouse model, we found that treatment with S. cerevisiae 48338 reduced disease severity, as reflected by lower clinical sickness scores. Quantitative PCR analysis confirmed that the expression of the toxin gene tcdA was significantly decreased following 48338 treatment, whereas total C. difficile burden remained unchanged. In addition, 48338 treatment might enhance intestinal barrier integrity by upregulating occludin gene expression and also might attenuate production of pro-inflammatory cytokines, particularly the expression of IL-1β. The strain also increased the proportions of Foxp3⁺ regulatory T cells and macrophages in both the spleen and mesenteric lymph nodes, as determined by flow cytometry, suggesting a shift towards an anti-inflammatory immune profile. Collectively, these findings suggest that the primary mechanism by which S. cerevisiae 48338 exerts its protective effect against C. difficile infection is not through direct reduction of C. difficile colonization, but primarily through modulation of the microbiome, host immune response, and maintenance of epithelial cell integrity. This study highlights the potential of yeast-based probiotics as adjunctive agents for the prevention or mitigation of CDI.

Antimicrobial resistance poses a significant threat to global health. Host defense peptides (HDPs) are being investigated as a strategy to mitigate this threat. Porcine β-defensins (pBDs) are a class of HDPs present in the swine immune system. Our group previously identified pBD‑5 as a component of the innate immune system of pigs and found that a synthetically produced cysteine-protected analogue modulated gene expression in swine gut cells in response to Brachyspira hyodysenteriae infection but lacked direct antimicrobial activity. In this study, we synthesized pBD‑5 with three disulfide bonds using orthogonal protection strategies and evaluated its antimicrobial activity, structural stability at pH 7, and cytocompatibility with swine red blood cells. Circular dichroism spectroscopy revealed a secondary structure predominantly composed of β-sheets and random coils, a conformation reported for other β-defensins. Using a paired study design with three technical replicates per group, we assessed pBD-5 antimicrobial properties at eight concentrations (1.56-200 µM) against Escherichia coli and Staphylococcus epidermidis. Growth inhibition was measured by optical density (OD₆₀₀ nm) and confirmed through colony-forming unit (CFU) counts on agar plates. Dose-dependent antimicrobial activity was observed, with significant growth reductions at 100 µM for CFU assays (S. epidermidis: 2-log reduction, P = 0.0318; E. coli: 1-log reduction, P = 0.0474) and 25 µM for OD₆₀₀ nm measurements (P < 0.001). Cytocompatibility assays revealed statistically significant hemolysis only at the concentration of 240 µM (P = 0.0009), highlighting the peptide's cytocompatibility at antimicrobial concentrations. While pBD-5 demonstrated modest antimicrobial properties compared to other AMPs, its cytocompatibility suggests potential for further investigations, including in vivo experimentation.

Growing evidence has suggested that probiotic consumption can decrease the incidence of Atopic dermatitis (AD) in infants and children. However, even meta-analyses have reported uncertain findings. The current umbrella meta-analysis aimed to assess the findings of multiple meta-analyses on the efficacy of probiotic supplementation on AD and other atopic manifestations in infants and children. A systematic search of the Literature was carried out in PubMed, ISI Web of Knowledge, Scopus, Cochrane Central Library, EMBASE, and Google Scholar from inception up to September 2024. Random-effects model was utilized when there was a significant between-study heterogeneity; otherwise, fixed-effects model was employed. The quality of the selected meta-analyses was assessed using a measurement tool to assess multiple systematic reviews 2 (AMSTAR2). Of the 1302 articles identified in the search, 22 articles that met the criteria were included in the present comprehensive umbrella meta-analysis. Findings indicated a notable decrease in AD severity based on WMD (ES = -4.16; 95%CI: -6.75, -1.57, p < 0.000) and Eczema (ES = 0.75; 95% CI: 0.69,0.81, p < 0.000) among infants. Subgroup analysis showed that factors such as type of probiotic, sample size, duration, and population were not significant sources of heterogeneity. Our research suggests that probiotics could play a beneficial role in managing AD and eczema. However, we found no statistically significant link between probiotic use and IgE levels, wheezing, allergies, or asthma.