Probiotics and Antimicrobial Proteins最新文献

The gut microbiome is crucial for human health, and its imbalance, known as dysbiosis, is associated with diseases such as inflammatory bowel disease, metabolic disorders, and neurological disorders. Traditional treatments, such as probiotics and fecal microbiota transplants, often lack precision, making the emerging field of nanomedicine a promising alternative. This review introduces the "MOF-Microbiome Axis," which explores the interactions between metal-organic frameworks (MOFs), versatile, porous materials, and the gut microbiome. It focuses on designing gastrointestinal-targeted MOFs that are biocompatible and responsive to stimuli. We discuss how MOFs can serve as scaffolds, controlled-release vehicles, and metabolite scavengers, highlighting their therapeutic applications in targeted antimicrobial therapy, enhanced probiotic delivery, and immunomodulation. The review also addresses important challenges in biosafety, scalable production, and personalized treatment, suggesting future directions such as bio-hybrid systems and precision microbiome editing. Overall, the MOF-Microbiome Axis offers a new perspective on microbiome engineering and advanced therapeutic approaches.

Diarrhea, a common gastrointestinal disorder, is often exacerbated by conventional antibiotic treatments that disrupt gut microbiota, necessitating the exploration of Lactic acid bacteria (LAB) alternatives. This study investigates the therapeutic potential and mechanisms of Streptococcus thermophilus NCU074001 (ST) in a rat model of PEG3350-induced osmotic diarrhea. ST treatment mitigated diarrheal symptoms and improved key markers of intestinal health by acting as a key modulator of the gut ecosystem. Its efficacy was driven by balancing immune responses via elevated IL-10 and suppressed pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, IFN-γ). Furthermore, ST reinforced the intestinal barrier by upregulating MUC2 expression and reshaping gut microbial ecology by suppressing certain genera (Bacteroides and Anaerofilum) while enriching others (Lactobacillus, Akkermansia, Phascolarctobacterium, and Parabacteroides). This taxonomic restoration was accompanied by a functional metabolic shift, characterized by increased production of short-chain fatty acids (acetate and butyrate) and a targeted modulation of tryptophan metabolism that enhanced the production of anti-inflammatory indole derivatives. Correlation analyses suggested potential links between ST-mediated microbiota remodeling and barrier strengthening and immunomodulation. Collectively, these results indicate that ST functions as a promising probiotic integrating immunomodulation, microbiota restoration, and metabolic reprogramming to alleviate diarrhea, and thus presents a promising therapeutic alternative to conventional antibiotics.

Aquaculture faces increasing challenges related to disease management and the need for sustainable alternatives to antibiotics that ensure productivity, fish welfare, and environmental sustainability. Probiotic bacteria, particularly lactic acid bacteria (LAB), have emerged as promising candidates for improving fish health through intestinal colonization, competitive exclusion of pathogens, and production of bioactive compounds. This study reports the phenotypic and genomic characterization of four Pediococcus pentosaceus strains (BE2, BE6, BE8, and BE9) isolated from the intestinal microbiota of freshwater fish (Cichlasoma spp.). Safety assessments revealed no hemolytic activity, coagulase production, or gelatinase activity, and antibiotic susceptibility profiles were consistent with international guidelines for probiotic candidates. The isolates demonstrated in vitro tolerance to acidic pH and bile salts, with viable counts decreasing by less than 2 log units under simulated gastrointestinal conditions. Adhesion assays using human Caco-2 cells showed approximately 30% adhesion efficiency. All strains exhibited growth on prebiotic substrates, including mannan oligosaccharides (MOS), fructo-oligosaccharides (FOS), and inulin (INU), with strain-specific preferences. Genomic analyses confirmed species-level identity and revealed biosynthetic gene clusters associated with the production of vitamins such as riboflavin, bacteriocins including penocin A and pediocin PA-1, alongside intrinsic resistance and stress response genes. Cell-free supernatants inhibited key aquaculture pathogens (Streptococcus agalactiae, Aeromonas hydrophila, and Francisella orientalis) in agar diffusion assays, suggesting antimicrobial potential mediated by bacteriocins identified in your genome. Therefore, the isolated strains exhibit promising functional and genomic characteristics, supporting their potential use as probiotics and components of synbiotic consortia for aquaculture applications.

The emergence of antibiotic-resistant pathogens has raised growing concern in aquaculture, prompting the development of probiotic-based strategies for disease control. In this study, a novel strain of Lactococcus lactis (LZK-02) was isolated from the intestine of healthy largemouth bass (Micropterus salmoides) and evaluated for its probiotic properties and immunomodulatory potential. The strain was identified through polyphasic taxonomy, including morphological characterization, 16 S rRNA gene sequencing, and whole-genome analysis. In vitro assays showed that LZK-02 exhibited strong antagonistic activity against Staphylococcus aureus, along with acid and bile tolerance, auto-aggregation, surface hydrophobicity, and digestive enzyme production. Genome annotation revealed genes related to stress resistance, adhesion, and bacteriocin biosynthesis. A feeding trial was conducted using diets supplemented with 10⁷-10⁹ CFU/g of LZK-02 for eight weeks. Results showed significant improvements in growth performance, intestinal histomorphology, antioxidant enzyme activities (SOD, CAT), and immune parameters (ACP, AKP, lysozyme) in treated groups compared to the control. Following intraperitoneal challenge with S. aureus, LZK-02-fed fish exhibited higher survival rates and lower bacterial loads in the liver. These findings suggest that L. lactis LZK-02 is a safe and effective probiotic candidate capable of enhancing immune responses and disease resistance in largemouth bass, and may serve as a potential alternative to antibiotics in intensive aquaculture.

Obesity is a global health challenge, but current pharmacological interventions (e.g., orlistat) often cause adverse effects. Although probiotics show potential in alleviating obesity, the mechanisms by which microencapsulated compound probiotics exert anti-obesity effects via peroxisome proliferator-activated receptors (PPARs) remain unclear. Our previous study demonstrated that pectin beads encapsulating compound probiotics (Lactiplantibacillus plantarum, Limosilactobacillus fermentum, Bifidobacterium breve) exhibited superior anti-obesity effects to single strain in high-fat diet (HFD)-fed rats. Here, we systematically investigated the alleviating effects of these microencapsulated compound probiotics (1 × 10⁸ CFU/day, oral gavage) against HFD-induced obesity in C57BL/6J mice (8-wk intervention) via PPARs-mediated regulatory mechanisms, with orlistat (24 mg·kg^- 1·day^- 1, oral gavage) as the positive control. Results showed that the microencapsulated compound probiotics significantly reduced weight gain rate (35.68% vs. 58.51% in HFD group, P < 0.05) without affecting food intake, improved hepatic steatosis (reduced hepatocyte vacuolation), and maintained glucose homeostasis (oral glucose tolerance test AUC: 14205 vs. 2150 mg·min/dL in HFD group, P < 0.05). Compared to HFD controls, the probiotics significantly reduced serum total cholesterol (2.90 vs. 6.31 mM, P < 0.05) and interleukin-6 (IL-6: 10.04 vs. 17.66 pg/mL, P < 0.05). Mechanistically, the probiotics downregulated PPAR-γ (0.65-fold vs. HFD, P < 0.05) to inhibit adipogenesis. 16 S rRNA sequencing revealed that the probiotics preserved gut microbial diversity (Shannon index: 5.2 vs. 4.1 in HFD group, P < 0.05), whereas orlistat caused gut dysbiosis (Shannon index: 3.8, P < 0.05 vs. ND group). Together, these findings clarified that microencapsulated compound probiotics alleviate obesity via PPAR-mediated lipid metabolism regulation, while protecting gut ecology-offering a safe and effective microecological strategy for obesity prevention.

The incidence of fungal infections has increased markedly in recent years, driven by increasing resistance to conventional antifungal agents. To address this challenge, the World Health Organization has highlighted the urgent need for novel antifungal molecules, particularly those that can enhance the efficacy of existing drugs. Synthetic peptides (γAFPs), derived from conserved γ-core motifs (GXC-X_3 - 9-C) of antifungal proteins, represent a potential source of such combination partners. Here, we systematically screened 19 γAFPs of various fungal origins and physicochemical properties to assess their activity and interaction with conventional agents. The intrinsic antifungal activity of these peptides was primarily governed by their net positive charge and hydrophilicity, with the charge-to-hydropathy ratio emerging as a strong predictor of efficacy. From this panel, two peptides (γAFP^B6GXZ8 from Penicillium rubens and γAFP^A0A2J5HZT4 from Aspergillus taichungensis) were identified as the leading candidates with potent antifungal activity mediated by the disruption of the plasma membrane. Although their standalone antifungal potency was modest, both peptides exhibited robust synergistic interactions with clinically used antifungal agents in vitro: γAFP^B6GXZ8 enhanced terbinafine efficacy against Candida albicans, while γAFP^A0A2J5HZT4 potentiated fluconazole activity against Aspergillus fumigatus. In a Galleria mellonella infection model, neither the peptides nor their combinations with conventional antifungal agents caused host toxicity, and effectively prevented C. albicans infection and prolonged the survival of larvae infected with A. fumigatus. These findings confirm that the synergistic effects observed in vitro can be maintained in vivo. Collectively, our findings identify two γ-core-derived peptides as well-tolerated synergistic co-therapeutics that augment antifungal drug efficacy and constitute promising templates for directed optimization.

Recently, a dental nanofloss containing a probiotic (Ligilactobacillus salivarius; LS-nanofloss) was developed by our team. This study aimed to evaluate: (i) its impact on subgingival plaque accumulation and gingival bleeding, and (ii) retention of selected subgingival periopathogens and the introduced probiotic bacteria, and (iii) its effect on the quantity of red complex periopathogens in the subgingival environment. This randomized, double-blind, crossover trial was conducted in 30 healthy male participants. Each subject underwent professional flossing and subsequently used LS-nanofloss/probiotic-free (control) nanofloss at two separate 14-day periods, always followed by a 14-day wash-out. Clinical assessments (subgingival plaque accumulation and gingival bleeding) were performed at five time points; subgingival plaque samples were collected at seven time points for quantitative analysis of total bacterial DNA, L. salivarius, a cariogenic bacterium Streptococcus mutans, and red complex periopathogens. Both nanofloss types significantly reduced plaque accumulation and gingival bleeding after 14 days (p < 0.05), especially in the anterior regions; these improvements, however, regressed after the wash-out period. L. salivarius DNA was detected in 93.3% of samples after professional flossing, 36.7% after self-flossing, and 13.3% even after the wash-out period. The use of LS-nanofloss was associated with a significant reduction in red complex periopathogens (p < 0.05). The investigated L. salivarius-containing nanofloss proved to be an effective oral hygiene device for subgingival introduction of this probiotic strain. Its application reduced the relative quantity of red complex periopathogens in the subgingival environment, showing potential to prevent the development of periodontitis. The trial was registered retrospectively on 2/9/2025 as NCT07149493.

The clinical consequences of biofilm-related infections are on the rise. Biofilm-related infections represent a mounting burden on healthcare worldwide, posing a significant challenge to patient care and health infrastructure. Another notorious function that needs to be underlined is the association of biofilms with medical devices. Considering the fact that bacteria under biofilm make them virulent and resistant to antibiotics, targeting the biofilms is a crucial area of investigation. Therefore, alternative approaches that extend beyond conventional antibiotic therapies are necessary to overcome biofilm-related infections. In this regard, Lactiplantibacillus plantarum, a probiotic bacterium, has lately shown promising outcomes as an antibiofilm agent. Largely renowned for its antimicrobial metabolite production, L. plantarum could be a potential alternative to improve biofilm-related treatment and its cost associated with biofilm infections. Therefore, the present review aims to provide a comprehensive understanding and implications of L. plantarum as an antibiofilm agent regardless of its biological form against pathogens in healthcare. Additionally, the potential of L. plantarum as a biofilm producer and its engineered applications in clinical applications and therapeutic use will also be discussed in this review.

Alcohol-associated liver disease (ALD) is a severe liver disease caused by excessive alcohol consumption. ALD remains a clinical challenge with limited therapeutic options. Following 5-day pretreatment with Lactobacillus acidophilus (Lac), mice were administered ethanol by gavage to induce ALD. Tissues were collected and analyzed for serum markers, hepatic pathology/inflammation/oxidative stress, ileal morphology/tight junctions, and cecal microbiota via 16 S rRNA gene sequencing. The fecal microbiota transplantation (FMT) experiment was performed, and tissues were then collected and analyzed as above. Moreover, the anti-inflammatory and antioxidant properties of Lac-derived particulate matter (pLac) were evaluated on RAW264.7 macrophages in vitro. Lac administration improved gut microbiota composition, enhanced intestinal barrier integrity and reduced lipopolysaccharide (LPS) translocation to the liver, thereby inhibiting the toll-like receptor 4 (TLR4)/ nuclear factor kappa B (NF-κB) pro-inflammatory pathway and activating the adenosine monophosphate activated protein kinase (AMPK)- peroxisome proliferator activated receptor α (PPARα) signaling axis. This led to significant attenuation of hepatic inflammation, oxidative stress and steatosis. The FMT experiments further validated that Lac-mediated protection is dependent on gut microbiota modulation. In vitro studies revealed that pLac exhibit direct anti-inflammatory and antioxidant properties. These findings elucidate the mechanistic basis for Lac in alleviating acute ALD, positioning it as a promising treatment or dietary intervention to enhance clinical management.