Probiotics and Antimicrobial Proteins最新文献

Bacteroides ovatus (B. ovatus), a key member of the gut microbiota, is strongly associated with host health, thereby emerging as a promising candidate for the development of next-generation probiotics. This bacterium is linked to various pathophysiological conditions and shows potential probiotic biological activity, particularly in modulating metabolism and treating certain diseases. In the present review, we aim to provide a comprehensive synthesis of the established biological attributes of B. ovatus, while also elucidating the patterns and characteristics of its abundance fluctuations across diverse clinical indications. We also investigate the influence of probiotics, prebiotics, natural products, dietary patterns, and other extrinsic factors on the dynamic changes in B. ovatus abundance. Additionally, an evaluative and prospective analysis of the potential applications of B. ovatus in the realms of functional nutrition and specialized medical foods is presented. Finally, we highlight the transformative potential of B. ovatus in functional nutrition and specialized medical foods, providing a basis for the development of novel microbiome preparations.

Selenium (Se)-enriched probiotics have gained widespread application in the fields of food, nutraceuticals, and biomedicine due to their capacity to deliver organic Se with high nutritional value to their hosts. Here, the inorganic Se bioconcentration was employed to generate Se-enriched Akkermansia muciniphila (Se-AM), and we investigated its Se distribution, selenoprotein and selenoamino acid species, essential elements, and amino acid contents. Furthermore, the major probiotic properties of Se-AM were evaluated. The results showed that the Se-AM exhibited remarkable survival and Se enrichment levels. The organic Se content in Se-AM accounted for approximately 81.9%, predominantly composed of protein bound Se (44.3%), followed by nucleic acid bound Se (17.8%) and polysaccharide bound Se (17.4%). The Se element in Se-AM exhibits a preference for binding to proteins with medium molecular weight, predominantly forming selenoamino acids containing SeCys2 and SeMet. Moreover, the content of both individual and total amino acids is higher in Se-AM compared to AM. Furthermore, Se-AM demonstrates robust acid resistance and antioxidant activity along with enhanced adhesion to Caco-2 and HT-29 cells. It also possesses immune-stimulating properties by activating the TLR4/NF-κB signaling pathway in Raw 264.7 cells, leading to increased cytokine release. Transcriptomic analysis reveals elevated expression levels of key genes associated with potent antioxidants, strong cellular adhesion capabilities, and effective cancer cell eradication within Se-AM when compared to AM. Our findings indicated that the Se-AM holds promising potential as a novel probiotic formulation supplemented with Se for both its Se-enhancing properties and probiotic functionality.

Helicobacter pylori (H. pylori) is a highly prevalent gastrointestinal infection associated with peptic ulcers, gastritis, and psychological disorders like anxiety and depression. This study explored whether probiotic supplementation with Lactobacillus rhamnosus (L. rhamnosus) and/or Lactobacillus plantarum (L. plantarum) could mitigate anxiety- and depressive-like behaviors in H. pylori-infected rats. In addition, specific biochemical mechanisms underlying H. pylori and probiotic effects were investigated. Rats were infected with H. pylori and treated with L. rhamnosus, L. plantarum, or both probiotics via oral gavage. Anxiety- and depression-like behaviors were assessed using open field, elevated plus maze, forced swimming, and marble burying tests. Oxidative stress markers, inflammatory cytokines, brain-derived neurotrophic factor (BDNF), serotonergic function, and corticosterone level were quantified in cortical tissues. Both L. rhamnosus and L. plantarum, particularly when co-administered, potently reversed the anxiogenic and depressogenic effects of H. pylori infection. These behavioral rescues were paralleled by normalization of dysregulated cortical oxidative and inflammatory parameters including suppressed anti-inflammatory cytokine IL-10 and reduced antioxidant defenses. Similarly, H. pylori-induced attenuation of neurotrophic capacity and serotonin availability alongside heightened corticosterone level were all opposed by L. rhamnosus and L. plantarum supplementation. Our integrative methodology provided pivotal evidence that multispecies probiotic intervention with L. plantarum and L. rhamnosus alleviates anxiety/depressive-like symptoms in a preclinical model of gastrointestinal inflammation. We propose that adjunctive probiotic therapy could promote the behavioral resilience by optimizing the redox regulation, suppression of inflammatory response, enhancement of neurotrophic support, and maintenance of serotonergic transmission in brain cortex. These data signify probiotic supplementation warrants further evaluation in infected patients with psychiatric comorbidities.

Antimicrobial peptides (AMPs) constitute a chemically and structurally heterogeneous family of molecules produced by a wide range of living organisms, including plants, fish, amphibians, mammals, and insects. Their expression is particularly high in hosts frequently exposed to microorganisms, where AMPs play a key role in innate immune responses. Insects represent one of the richest natural sources of AMPs. Over their long evolutionary history, they have developed a highly efficient immune system with AMPs playing a central role in defense against pathogens, enabling them to colonize various habitats. In recent years, interest in AMPs has significantly increased due to the emergence of antibiotic resistance, positioning these peptides as potential therapeutic alternatives for treating infections caused by multi-resistant pathogens. In this study, we investigated the antimicrobial activity of peptide fractions extracted from the hemolymph of Hermetia illucens larvae (Diptera, Stratiomyidae), an insect known for its high expression of AMPs. Larvae were injected separately with either Escherichia coli (Gram-negative) or Micrococcus flavus (Gram-positive), and hemolymph was collected 24 h post-infection, as well as from uninfected larvae. Antimicrobial activity was assessed through microbiological assays, including both agar diffusion tests and microdilution assays. Results demonstrated significant activity against pathogenic bacterial strains, including antibiotic-resistant ones. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were determined for each experimental condition. MIC values ranged from 0.023 to 0.375 µg·µL⁻¹, while MBC values ranged from 0.187 to 0.750 µg·µL⁻¹, depending on the bacterial strain and the infection treatment group. These findings demonstrate the potential of H. illucens-derived AMPs as effective agents against Gram-positive and Gram-negative bacteria, including resistant strains, and support their further development as alternatives or adjuvants to conventional antibiotics.

Postmenopausal osteoporosis is a common bone disease characterized by bone loss due to the disruption of bone homeostasis caused by decreased estrogen levels. It is estimated that approximately one third of women over the age of 50 will experience osteoporosis in their lifetime. Therefore, developing functional foods or treatments that can be safely consumed to prevent bone disease is essential. Recent studies have reported that gut microbiota is closely related to the development of osteoporosis. In this study, we confirmed that Lactobacillus sakei CVL-001 (CVL-001) and its metabolites (CVL-001S) alleviate OVX-induced bone loss. Furthermore, they inhibited RANKL-induced osteoclastogenesis by regulating NFATc1 expression. Imbalance in the gut microbiota also affects the release of cellular components such as lipoteichoic acid and exopolysaccharides from beneficial bacteria (e.g., lactic acid bacteria), as well as production metabolites such as short chain fatty acid. Therefore, to investigate the association between CVL-001S-mediated inhibition of osteoclast differentiation, we used osteoclast precursor cells isolated from TLR2 KO mice and the GPCR inhibitor. Although the inhibitory effect of CVL-001S on osteoclast differentiation could not be fully rescued by either the TLR2 KO cells or the GPCR inhibitor alone, pretreatment of TLR2 KO cells with the GPCR inhibitor completely abolished the inhibitory effect of CVL-001S on osteoclast differentiation. These results suggest that CVL-001S inhibits RANKL-induced osteoclast differentiation through the cooperation of TLR2 with GPCR. Our results suggest that CVL-001S and CVL-001 can be a potentially therapeutic agent for preventing or treating bone disease.

In general, endodontic infections are polymicrobial infections, and the severity of the infection depends on the pathogenicity of the microbes and the resistance of the host. For the treatment of endodontic infections, antibiotics are widely used; however, the development of resistance raises concerns for their wide-scale application; hence, there is always an unmet need to develop alternative treatment strategies in the fight against endodontic infection. Basically, the searches were conducted in PubMed (459), Science Direct (559 articles), and WOS (493) using keywords and phrases to identify relevant articles. Search criteria consisted of combinations of the following words and phrases: Bioactive peptides, endodontic infections, oral microbiota, intraradicular infections, extraradicular infections, In vitro, In vivo study, clinical trials, mechanism of peptides, oral biofilm. It is important to note that bioactive peptides are short sequences of 2-40 amino acids, displaying various functional and structural diversities, and exhibiting a wide range of therapeutic activity. This comprehensive review discusses various aspects related to bioactive peptide sources; chemistry; biosynthesis; bioavailability; safety along with the periradicular disease, oral microbiota, and microbial analysis; molecular mechanisms of pathogenicity; host susceptibility; prediction markers; focal infection; and bioactive peptide resistance as well as approaches to overcome peptide resistance. Overall, this review will enlighten the readers with the prospective potential of bioactive peptides against endodontic infections.

This study aimed to produce a new functional Beyaz cheese variety with the addition of different ratios (0.5% and 1%) of walnut leaf powder (WLP) and probiotic bacteria (Lactobacillus acidophilus LA-5.). The probiotic shelf-life and techno-functional properties of Beyaz cheeses were investigated at 30-day intervals during ripening in brine (120 days at + 4 °C). The highest acidity, ash, salt, Fe, Cu, Mn, a*, b*, H°, and C* values were found in the WLP-supplemented cheeses compared with those in the control without probiotic (C) and probiotic control (PC) cheeses (p < 0.01). The count of L. acidophilus LA-5 in probiotic cheeses decreased to less than 10⁶ colony-forming units (CFU)/g after the 60th day of storage. Compared with PC (77.52%), WLP increased the viability rate (82.04-86.52%) over the 60-day shelf-life period. The total phenolic content (TPC), total flavonoid content (TFC), chlorophyll a and chlorophyll b contents, and total antioxidant activity (DPPH•, CUPRAC, and FRAP assays) of the cheeses significantly increased with the addition of 0.5 and 1% WLP (p < 0.01). The addition of WLP increased proteolysis (WSN, pH 4.6‒SN, TCA‒SN and PTA-SN) and lipolysis (p < 0.01). The general acceptability of cheese samples was PC > C > PWL_0.5% > PWL_1%. Consequently, a new variety of functional Beyaz cheese with a probiotic shelf life of 60 days that is rich in bioactive compounds and microminerals (Fe, Cu and Mn) and natural for healthy nutrition can be produced with the addition of L. acidophilus LA-5 and 0.5% WLP.

Vulvovaginal candidiasis (VVC), primarily caused by Candida albicans, is a common fungal infection that typically causes inflammation and discomfort. Current antifungal treatments, such as fluconazole, are associated with adverse effects and drug resistance, highlighting the need for alternative therapies. In this study, we investigated the antifungal efficacy of Limosilactobacillus fermentum 21N1 (LF21) against C. albicans using both in vitro assays and a murine model of VVC. A spotting assay assessed the inhibitory activity of LF21 against C. albicans. A murine VVC model was established by intravaginally inoculating C. albicans. Fungal burden, inflammation, and histopathological changes were assessed using colony counting, H&E, and PAS staining. Immunofluorescence and Western blot analyses quantified the expression of NLRP3 inflammasome and pyroptosis-related proteins. In vitro experiments using a spot formation assay revealed that LF21significantly inhibited C. albicans growth. Additionally, oral administration of LF21 alleviated VVC symptoms in mice inoculated with C. albicans, reducing the vaginal fungal burden and IL-1β levels. Histological analysis revealed reduced polymorphonuclear neutrophil infiltration and decreased C. albicans presence in the vaginal tissues of LF21-treated mice. LF21 treatment significantly reduced the expression of NLR family pyrin domain containing 3 (NLRP3) inflammasome components and pyroptosis-related proteins, including gasdermin-D, which were upregulated in response to the inoculation of C. albicans. These findings suggest that LF21 exerts antifungal effects by modulating the NLRP3 inflammasome and consequently reducing inflammation, indicating its potential as a novel therapeutic agent for treating VVC.

Melittin (MLT), an antimicrobial peptide, is considered due to its wide range of antimicrobial properties against Gram-negative and Gram-positive bacteria. In this study, we performed in silico and in vitro studies for the evaluation of the synergistic effect of M1 and M2 peptides derived from MLT to limit vancomycin intermediate E. faecalis. Results obtained from coarse-grained simulations indicated significant destruction during the penetration of the M1 and M2 peptides into the E. faecalis membrane model. The trajectory results also revealed notable movements of 2.381 nm and 2.758 nm within the membrane for M1 and M2 peptides, respectively. The synergistic effect of MLT, M1, and M2 peptides with vancomycin was evaluated to inhibit the growth of a VIE clinical isolate using the established checkerboard method. MTT assays and hemolysis tests were conducted to examine the toxicity of the peptides. The combination therapy of vancomycin with the peptides led to an 80-fold reduction in the MIC value of vancomycin (from 8 to 0.125 µg/ml). In contrast, it led to a 13.33-fold reduction in the MIC value of MLT, an eightfold decrease in the MIC value of both M1 and M2 peptides. Based on FICI values, a synergistic effect was observed between MLT, M1, and M2 with vancomycin. MTT assay and hemolysis results indicated a notable reduction in the toxicity of the peptides at the synergistic concentrations. In conclusion, the combination therapy of MLT and M1 and M2 peptides with the vancomycin antibiotic could be an appealing therapeutic strategy against E. faecalis infections.

Inflammation and oxidative/nitrosative stress (O&NS) are serious complications in non-communicable diseases (NCDs), including endocrine and metabolic and neurodegenerative diseases. The beneficial probiotic microbes, such as Lactobacillus, Bifidobacterium, and Streptococcus, can decrease O&NS and inflammation. We conducted this systematic review and meta-analysis of randomized controlled trials (RCTs) with aims to elucidate the effects of probiotics on O&NS and inflammation in NCDs. A systematic search of PubMed, Scopus, and EMBASE resulted in the inclusion of studies if they met the eligibility criteria. Methodological quality was assessed using the Cochrane Risk of Bias 2 tool. Data (combined effect size) were analyzed using Meta-Essentials software. Fifteen studies/16 trials with a total of 807 participants (421 cases/386 controls) were reviewed. There was high and moderate certainty of evidence (GRADE) for the effectiveness of probiotic intervention (vs. placebo) in increasing (↑) glutathione (GSH) levels (SMD(SE) = 0.89 (0.51)/p < 0.05, 95%CI - 0.23 to 2.1, I² = 92.77%) and total antioxidant capacity (TAC) (SMD(SE) = 0. 75 (0.22)/p < 0.01, 95%CI 0.28 to 1.23, I² = 87.50%) as well as decreased (↓) malondialdehyde (MDA) (SMD(SE) = 1.03 (0.31)/p < 0.01, 95%CI 0.37 to 1.7, I² = 93.88%) and C-reactive protein (hsCRP) (SMD(SE) = 0.74 (0.36)/p < 0.05, 95%CI - 0.07 to 1.55, I² = 94.32%). There were no effects on nitric oxide, 8-hydroxy-2'-deoxyguanosine, interleukin-6, and tumor necrosis factor-α. Subgroup analysis to reduce heterogeneity indicated probiotic effectiveness on strain number (one/↑GSH), age bracket (41-60 years/↓MDA or > 61 years/↓hsCRP), and NCD (nervous system/neurodegenerative diseases/↑GSH and ↓hsCRP or rheumatoid arthritis/polycystic ovary syndrome/↑TAC). An overall low risk of bias was observed. In conclusion, probiotics may have beneficial effects on markers of O&NS and inflammation in patients with NCDs.