Competitive combat athletes are routinely exposed to high training loads, rapid weight-making practices, psychological stress, and frequent injuries-all of which may adversely affect the gut microbiome and, consequently, multiple physiological systems relevant to performance. Growing scientific interest in the role of probiotics and host-microbiome interactions suggests that targeted modulation of gut bacteria may offer functional benefits for athletes. This narrative review synthesizes current evidence on probiotics and microbiome-mediated pathways influencing performance, recovery, and health in combat-sports athletes. A comprehensive literature search was conducted across PubMed, Web of Science, and Google Scholar, with no date limits, including studies published up to October 2025. Search terms covered the gut microbiome, probiotics, athletic performance, combat sports, gastrointestinal barrier function, immune responses, psychological factors, nutrient absorption, hypoxia, weight cutting, and sex-specific considerations. Reference lists of relevant reviews and grey literature were manually screened. Across the available literature, probiotic supplementation has been associated with a range of effects that could be relevant to combat athletes. Evidence, largely from non‑combat and mixed‑population studies, suggests that probiotics may influence several physiological systems, including: (1) inflammatory and oxidative stress responses and injury rehabilitation; (2) immune function and upper respiratory tract infection outcomes; (3) gastrointestinal permeability and nutrient absorption, particularly after rapid weight loss; (4) psychological factors via the gut-brain axis; (5) muscle recovery through inflammatory and metabolic pathways; (6) body composition and weight regulation; (7) oral and skin microbiome composition; and (8) gut microbial changes during hypoxia or hormonal fluctuations. However, most of these findings are indirect, with very few studies conducted specifically in competitive combat‑sport athletes, and the overall evidence base remains heterogeneous. Probiotic and gut microbiome-targeted strategies may serve as potential adjunctive strategies to support health, recovery, and performance in combat athletes. However, because the current evidence is largely derived from non-combat and predominantly male populations, strain-, dose-, and sport-specific recommendations cannot yet be made. There is a clear need for randomized controlled trials in combat-sport athletes-including women-that employ standardized probiotic protocols and sport-specific outcome measures.
Probiotics are increasingly recognized for their role in enhancing fish health, strengthening immune responses, and mitigating stress, particularly as rising inland water salinity continues to compromise fish health and reduce aquaculture productivity. To investigate the potential of probiotics as a countermeasure against the health and productivity challenges posed by brackish water, a 9-month feeding trial was conducted to evaluate the hematological and antioxidant responses of Labeo rohita (20.18 ± 0.22 g; Mean ± SD) reared in inland brackish water earthen ponds (mean area: 1.0 acre; depth: 1.5 m; salinity: 6.1 ppt) and fed diets with or without a multi-species probiotic (MSP) containing Bacillus subtilis (1.9 × 10¹⁰ "CFU/g"), Bacillus licheniformis (2 × 10¹⁰ "CFU/g"), and Clostridium butyricum (2.2 × 10⁸ "CFU/g"). A total of 900 fish were randomly distributed into three treatment groups (P I, P II, and P III), each with three replicate ponds. Fish in group pond P I (control) were fed a basal diet without probiotic supplementation, whereas fish in groups P II and P III received the same basal diet supplemented with MSP at 0.5% and 1%, respectively. A significant improvement (p < 0.05) in blood biomarkers was observed in the 1% MSP fed fish, even when reared at inland brackish water. Erythrocyte count, hemoglobin content, hematocrit count, total serum protein, albumin, and globulin were significantly higher (p < 0.05) in the 1% MSP fed fish compared to the non-probiotic-fed fish. A significant effect of rearing time on oxidative stress markers (ROS and TBARS) which increased over time and significant decline in antioxidant enzymes (SOD, CAT, POD, and GSH) were observed in brackish water ponds without probiotics (p < 0.05), however, dietary MSP supplementation significantly mitigated oxidative damage and enhanced antioxidant defenses in liver, kidney, and gills (p < 0.05). Frequency of erythrocytic alterations was also significantly reduced in MSP-supplemented groups compared to non-probiotic groups (p < 0.05). Marked recovery in histoarchitecture of liver, kidneys, and gills in MSP-supplemented groups compared to non-probiotics groups. In conclusion, dietary MSP supplementation effectively improved blood health and antioxidant capacity in L. rohita in inland brackish-water ponds, suggesting its practical potential to enhance health performance under brackish-water farming conditions.
The growing restrictions on in-feed antibiotics and the global rise of antimicrobial resistance have intensified the demand for safe and sustainable alternatives to support animal health and productivity. Paraprobiotics, defined as non-viable or inactivated bacterial cells, have recently emerged as a promising class of functional bioactives capable of conferring health benefits without the risks associated with live probiotics. Unlike conventional probiotics, paraprobiotics mediate their effects through intact cell structures and microbial metabolites that engage host pattern-recognition receptors, thereby modulating both innate and adaptive immune responses. This review critically examines the antimicrobial efficacy of paraprobiotics in poultry, emphasizing their mechanistic role in maintaining gut barrier integrity, regulating microbial ecology, and mitigating inflammation-induced oxidative stress. Evidence indicates that paraprobiotics suppress pathogenic colonization enhance epithelial function, stimulating antimicrobial peptide production, and improve nutrient utilization and growth performance. Moreover, their stability during feed processing, prolonged shelf-life, and minimal risk of horizontal gene transfer further enhance their suitability for large-scale, intensive production systems. Additionally, emerging inactivation technologies, optimized dosing strategies, and synergistic applications with prebiotics and phytobiotics offer avenues to maximize their functional potential. Collectively, paraprobiotics exemplify a paradigm shift in antimicrobial nutrition providing "dead cells with living functions" that combine safety, efficacy, and sustainability. Their integration into antibiotic-free poultry system hold significant promise for enhancing disease resilience, productive performance and overall sustainability of modern poultry production.
Despite the well-documented health benefits of non-spore-forming probiotics such as Lactobacillus and Bifidobacterium, their broader application can be constrained by limited stability and survivability during processing, storage and gastrointestinal transit. These limitations have driven growing interest in spore-forming bacteria belonging to Bacillaceae family for potential use as probiotics particularly for products that require heat processing or extended shelf-life. This review focuses on the genera Bacillus, Heyndrickxia and Priestia, which have established roles across biotechnology, food and industrial applications, with evidence demonstrating benefits in plants, animals and human nutrition. Key technological traits, carbohydrates and nitrogen metabolism capacities and bioactive outputs are highlighted in this review, including the production of enzymes, antimicrobial compounds such as bacteriocins and non-ribosomal synthesized peptides, as well as other metabolites relevant to host and microbiome modulation. The mechanistic basis underpinning reported functions, such as competitive exclusions, antimicrobial activity, and immunomodulatory effect are also discussed in the context of probiotic and postbiotic. Finally, translational considerations, challenges and outlook in spore-forming probiotic and postbiotic biosolutions are addressed, including strain specific efficacy, safety evaluation and long-term use, and the practical requirements for robust human validation. This review intends to provide a critical and comprehensive synthesis, to update and further encourage researchers and industry stakeholders in developing Bacillaceae-based probiotics and postbiotics that align with the market needs.
This study evaluated the influence of dietary supplementation with prebiotics, probiotics and synbiotics on growth performance, immune response, antioxidant capacity, antimicrobial peptides (AMPs) expression and disease resistance in juvenile olive flounder (Paralichthys olivaceus) fed a low-fish meal (LFM, 45% fish meal) diet. Experimental diets were formulated by supplementing an LFM diet (Con) with 0.6% mannan oligosaccharides (Mos), Lactiplantibacillus plantarum (LP), Bacillus subtilis (BS), B. licheniformis (BL) and their combination (Syn; 0.15% Mos, 0.15% LP, 0.15% BS and 0.15% BL). Fish (initial body weight: 65.9 ± 0.09g) were randomly distributed into triplicate groups and fed the experimental diets for 11 weeks. After the feeding trial, growth performance, feed utilization efficiency, survival, condition factor and somatic indices showed no significant variation among dietary groups. Similarly, immune parameters and hematological indices remained comparable across all treatments. Aspartate aminotransferase and alanine aminotransferase levels were lower, whereas antioxidant capacity was higher in all supplemented groups. After the Edwardsiella piscicida challenge, cumulative survival, immune parameters and antioxidant capacity were significantly higher in probiotics and Syn groups than in Con group. The expression of AMPs (hepcidin, β-defensin, LEAP-2, NK-lysin and pleurocidin) was significantly upregulated in fish fed LP, BS, BL and Syn diets, whereas prebiotic supplementation showed a minimal effect on AMPs transcription. Therefore, these results demonstrate that dietary probiotics and synbiotics effectively enhance immunity, antioxidant defense and disease resistance of P. olivaceus when fed LFM diets without compromising growth performance. These findings support the use of such additives as sustainable alternatives to chemotherapeutic agents in intensive P. olivaceus aquaculture.
Dengue virus (DENV), a member of the flavivirus family, is transmitted by the Aedes mosquito, with an incubation period of typically four to ten days, and causes a clinical spectrum of Dengue virus infection (DVI), ranging from classic dengue fever (DF) to sever illness, with symptoms such as vascular leakage, hemorrhage, organ dysfunction, and dysregulated inflammatory responses mediated by cytokines such as interleukin 6 (IL-6). However, Concerns about the absence of effective antiviral treatments or the efficacy and safety limitations of existing vaccines have led to considering novel treatment ways. Probiotics and postbiotics modulate mucosal and systemic immunity in a variety of ways, including mechanisms such as interaction with intestinal epithelial cells and dendritic cells (DCs), increased antigen (Ag) presentation, modulation of the toll-like receptor (TLR) signaling pathway, upregulation of regulatory pathways, and stimulation of antiviral cellular responses, including increased interferon-gamma (IFN-γ) production and cluster of differentiation 4+ (CD4+) and CD8+ T cell activity. According to the immunological properties, probiotics and postbiotics have been hypothesized to influence host responses related to DENV infection. Furthermore, probiotics have been proposed as a potential approach to modulate immune responses following dengue infection or vaccination; however, their role in alleviating antibody-dependent enhancement (ADE) is not yet clearly established. They may rather contribute as adjunctive immunomodulators or potential vaccine adjuvants, rather than as independent therapeutic agents. This review article shows a conceptual and perspective potential of probiotics and postbiotics through which they may integrate mechanistic insights and preclinical or clinical evidence, rather than implying immediate therapeutic applicability. This review includes mechanistic data and existing preclinical and clinical evidence, identifies key gaps in strain selection, dosing, molecular correlates of protection, and safety assessment, and suggests higher-priority research avenues, including adequately powered randomized controlled trials that measure clinical endpoints, immunological markers, and potential interactions with DENV vaccines and antibody-dependent risk enhancement.
Both conventional and next-generation probiotics play a crucial role in maintaining host homeostasis. They modulate insulin sensitivity, immune-regulation, lipid metabolism, and trimethylamine synthesis. In recent years, probiotics have emerged as an effective and safe alternative to antibiotics for treating chronic life-style disorders via gut-organ-axis. Accounting for that, they contributed a market size of 71.2 billion USD in the year 2024. However, effective consortia that can completely address all the symptoms of a particular disease are still lacking. Further, natural probiotics also face the issues of low survival rate and transfer of antibiotic resistance genes. Thus, postbiotics, which act as the ultimate mediators of gut-organ-axis have gained recognition over probiotics. They bind with multiple receptors present in host organs and modulate their functioning. This suggests the multilayer-multichannel axis between postbiotics and host vital organs. However, postbiotics cannot colonize the gut, and dosage and time also need optimization. Hence, engineered probiotics are being developed for efficient self-regulatory release of postbiotics at the target site. There are a few reviews on the topic of probiotics and lifestyle diseases; however, there is an urgent need for a critical appraisal synchronous with the fast-evolving technology, including omics and artificial intelligence. Thus, our article discusses advancements in technology to address the shortcomings of probiotics and postbiotics using genome editing, machine learning, and functional genomics techniques. It also covers the detailed application of artificial intelligence in probiotic consortia formulation, disease diagnosis, novel postbiotics detection, genetically engineered probiotics, and personalized therapies.
Gastrointestinal motility disorders (GIMDs) are prevalent conditions with heterogeneous symptoms and limited long term therapeutic efficacy. Increasing evidence indicates that gut dysbiosis contributes to the development and persistence of these disorders by impairing mucosal barrier function, inducing low-grade inflammation, and disrupting signaling within the enteric nervous system and the gut brain axis. Consequently, microbiota targeted interventions including probiotics, prebiotics, synbiotics, and postbiotics have attracted growing interest. This review summarizes recent advances across these four microecological strategies and integrates mechanistic insights relevant to multiple motility phenotypes. Probiotics regulate gastrointestinal motility through strain specific mechanisms involving reshaping of microbial communities and metabolic outputs, reinforcement of barrier integrity, modulation of immune inflammatory responses, and regulation of enteric neural and neuroendocrine pathways. Prebiotics selectively promote beneficial bacteria such as Bifidobacterium and Lactobacillus and increase the production of short chain fatty acids, thereby optimizing the intestinal microenvironment to support motility recovery. Synbiotics combine microbial strains with fermentable substrates to accelerate ecological restoration and often provide broader benefits on intestinal transit, barrier function, and neuroimmune regulation. Postbiotics enable targeted interventions independent of live colonization by directly influencing metabolism, barrier homeostasis, immune signaling, and smooth muscle function. Despite promising evidence, clinical translation is challenged by patient heterogeneity, variable study design, and limited comparative trials. Future research should emphasize mechanism driven precision strategies supported by multi omics stratification and rigorously designed multicenter randomized studies.
Yeasts of the Candida genus area major cause of infections regarding respiratory, digestive, and reproductive systems. Doderlin is an antimicrobial peptide isolated from Lactobacillus acidophilus and is notable for presenting a non-hemolytic effect. However, its long sequence and broad antimicrobial spectrum may limit its therapeutic applications. This study evaluated the antimicrobial activity, cytotoxicity, and morphofunctional effects of three Doderlin analogues (Dod H, Dod B, Dod T). Peptides were synthesized via Fmoc solid-phase synthesis. Antimicrobial activity and cellular effects were evaluated through growth assays, flow cytometry, and fluorescence and scanning electron microscopy. Among the analogues, Dod B exhibited the most promising antifungal activity, particularly against Candida albicans, while also inhibiting other clinically relevant Candida species, including Candida glabrata and Candida tropicalis. Notably, Dod B promoted the formation of interconnected cellular multi-aggregates and alterations in cellular physiology, potentially associated with interactions involving Seryl-tRNA synthetase (SerRS) and Peptidyl-prolyl isomerase ESS1. Although sequence optimization reduced the broad-spectrum activity observed for native Doderlin, it enhanced antifungal specificity and potency. These findings highlight Dod B as a promising therapeutic candidate for the treatment of Candida infections.
Bacterial extracellular vesicles (BEVs) are nanosized lipid bilayer structures released by both Gram-positive and Gram-negative bacteria. They transport proteins, lipids, metabolites, and nucleic acids. Increasing evidence indicates that BEVs function as active mediators of gut-organ communication rather than passive microbial byproducts. This review synthesizes current knowledge on BEV cargo composition, isolation strategies, and host interaction mechanisms with particular emphasis on gut-liver and gut-brain cross-talk. Within the intestinal environment, BEVs interact with pattern-recognition receptors, including Toll-like receptor (TLR) pathways, and influence epithelial barrier integrity and cytokine signaling. Under conditions of increased permeability, BEVs can reach systemic circulation and activate Kupffer cells (KCs) and hepatic stellate cells, contributing to inflammation and fibrosis. In contrast, vesicles derived from commensal species such as Akkermansia muciniphila enhance barrier function and improve metabolic signaling. In obesity and type 2 diabetes, BEVs modulate insulin signaling pathways, linking microbial activity to host glucose homeostasis. Moreover, certain BEVs can cross the blood-brain barrier and influence neuroinflammatory processes. Importantly, we propose a context-dependent framework in which BEV-mediated effects are determined by vesicular cargo composition, host cellular state, and exposure dynamics. This perspective helps reconcile the dual pathogenic and protective roles reported in the literature. Finally, we discuss current methodological limitations and outline key future directions. These include standardized isolation protocols, in vivo fate-tracking studies, and the development of engineered vesicle-based therapeutic strategies. A more precise understanding of BEV biology may enhance biomarker discovery and support targeted interventions in chronic metabolic and inflammatory diseases.
Non-alcoholic fatty liver disease (NAFLD), recently reclassified as metabolic dysfunction-associated steatotic liver disease (MASLD), is a prevalent metabolic disorder with significant inflammatory underpinnings. Emerging evidence underscores the gut-liver axis as a pivotal pathway in MASLD pathogenesis through which dysbiosis drives cytokine-mediated inflammation, fibrosis, and disease progression. This review synthesizes preclinical and clinical findings on how probiotics and prebiotics modulate key inflammatory cytokines-including TNF-α, IL-6, IL-1β, IL-10, IL-17, and TGF-β-to ameliorate MASLD. The literature demonstrates that these interventions converge on the TLR4/NF-κB axis as the central mechanistic driver of cytokine dysregulation in MASLD. By restoring gut barrier integrity and reducing endotoxin (LPS) translocation, probiotics and prebiotics suppress TLR4/NF-κB activation, which secondarily inhibits the NLRP3 inflammasome (reducing IL-1β/IL-18), downregulates pro-inflammatory cytokines (TNF-α, IL-6, IL-17), and enhances anti-inflammatory signals (IL-10) through crosstalk with PPAR-α, AMPK, and Nrf2 pathways. In animal models, probiotic strains such as Bifidobacterium, Lactobacillus, and Akkermansia muciniphila consistently downregulate pro-inflammatory cytokines and enhance anti-inflammatory signals. The same is true for prebiotics, including inulin, oat β-glucan, and synbiotic formulations. However, clinical trial outcomes remain heterogeneous, influenced by strain specificity, intervention duration, and patient heterogeneity. Collectively, this review highlights the therapeutic potential of microbiota-targeted interventions to rebalance cytokine networks and proposes future directions for personalized, mechanism-driven approaches to the management of MASLD.
The gut-associated lymphoid tissue (GALT) serves as the main immunological interface between fish and their aquatic environment, playing a central role in defense, homeostasis, and adaptation. Over the past two decades, probiotics have gained recognition as powerful tools for enhancing GALT function in teleost fish, influencing immunity, gut microbiota composition, and overall health. While previous reviews have addressed specific aspects of probiotic applications in aquaculture, a comprehensive synthesis linking immunological, microbiological, molecular, nutritional, and practical perspectives has been lacking. This review fills that gap by integrating these diverse domains into a unified analysis of probiotic-GALT interactions. Evidence indicates that probiotics promote beneficial shifts in gut microbial communities, support mucosal immunity through modulation of key immune cell populations and immunoglobulins, and contribute to improved growth and disease resistance. Despite promising results, challenges remain in translating laboratory findings into consistent field-level outcomes, particularly regarding strain stability, delivery methods, and host-specific responses. Future research should prioritize standardized evaluation protocols, advanced formulation technologies, and sustainable implementation strategies. By bridging disciplinary boundaries, this review provides a foundation for optimizing probiotic use to advance fish health and sustainable aquaculture.
This review paper examines various polymers and biomaterials used for probiotic encapsulation, with particular emphasis on how these materials aid in improving probiotic viability. Probiotics are living microorganisms that offer the host a number of beneficial health effects when given in the right amounts to the targeted area of the digestive tract. Despite the array of promised health benefits, the functionality of these probiotics depends on their retaining viability and sufficient cell concentrations at the point of ingestion and digestion. However, a number of factors can compromise the viability of these probiotics, such as pH fluctuations, temperature extremes, oxygen content, flavored additives, moisture activity, packaging and storage conditions. Encapsulation, which is the process of entrapping one substance into another substance, has emerged as an effective strategy to overcome the difficulties associated with preserving probiotic viability. It shields probiotics from extrinsic stressors, while enhancing their stability and promoting efficient delivery to the gut. Probiotic viability during processing, storage, and digesting is ensured by the robust defense against external stressors provided by the polymers and biomaterials utilized to encapsulate these organisms. Their adaptable nature enables incorporation into diverse food systems, such as drinks, baked products, and plant-based formulations, helping to meet the increasing consumer interest in gut health-oriented functional foods. Some biomaterials can also serve as prebiotics, enhancing the proliferation of these beneficial microorganisms. This review aims to highlight the main polymers and biomaterials employed in probiotic encapsulation, with emphasis on how they enhance the stability, functionality, and overall viability of probiotic cells.
Western dietary patterns are major drivers of cardiometabolic dysfunction, partly mediated by gut microbiome dysbiosis and sustained inflammation along the gut-brain axis. In this study, we investigated whether a synbiotic formulation combining Limosilactobacillus (L.) fermentum strains with polyphenols, quercetin, and resveratrol could mitigate cardiovascular and neuroinflammatory alterations induced by a Western diet. Male Wistar rats were assigned to three groups receiving a standard diet, a Western diet, or a Western diet supplemented with the synbiotic. Arterial pressure and cardiac autonomic function were assessed, alongside gut microbiome diversity and composition, and gene expression analyses of intestinal permeability and inflammatory markers in colonic tissue and in the brainstem. Synbiotic supplementation prevented the Western diet-induced cardiac autonomic imbalance. These functional benefits were accompanied by marked modulation of the gut microbiome, characterized by increased abundance of beneficial bacterial taxa (Gemmiger formicilis, Lactobacillus acidophilus, Flavonifractor plautii, Blautia glucerasea, Blautia stercoris, Roseburia faecis, Marvinbryantia formatexigens, and Romboutsia timonensis) and significant shifts in microbial community structure. In parallel, synbiotic supplementation attenuated pro-inflammatory gene expression in both peripheral and central tissues associated with the gut-brain axis (Nlrp3, Casp1, Il-1β). These findings demonstrate that synbiotic supplementation exerts integrated anti-inflammatory and neuroautonomic protective effects through the gut-brain axis. Our results support the therapeutic potential of combined probiotic-phenolic strategies to counteract cardiometabolic dysfunction induced by Western diets.
Lactobacillus helveticus LH76 is a candidate strain with potential probiotic properties, but its safety and functional effects have not been comprehensively characterized. In this study, we systematically evaluated the safety profile and potential immunomodulatory and gut microbiota-modulating effects of LH76 through integrated genomic, preclinical, and clinical approaches. Preclinical safety assessment included whole-genome sequencing and bioinformatics analyses (AMRFinder, CARD, ResFinder, VFDB, and PathogenFinder), in vitro assays of hemolysis, biogenic amine production, and cytotoxicity in Caco-2 cells, as well as a 14-day acute oral toxicity study in mice. An 8-week randomized, double-blind, placebo-controlled trial was subsequently conducted in healthy adults to assess safety, immune-related biomarkers (IgA, IgM, IgG, C3, C4, LL-37, and calprotectin), and gut microbiota composition by 16 S rRNA sequencing. LH76 showed no detectable antibiotic resistance or classical virulence genes, no hemolytic activity, negligible biogenic amine production, and no detectable cytotoxicity in vitro, while no adverse effects or pathological abnormalities were observed in vivo. In the clinical trial, LH76 was well tolerated and was not associated with adverse changes in hematological, biochemical, or metabolic parameters. Compared with placebo, LH76 supplementation was associated with increased serum IgM and C3 levels, decreased C4 and LL-37 levels, increased microbial richness, and relative enrichment of genera including Blautia and Bifidobacterium. PICRUSt2-based analysis further suggested shifts in predicted microbial metabolic pathways, although these findings remain inferential. Overall, LH76 demonstrated a favorable safety profile, was well tolerated in healthy adults at the administered daily dose of 3 × 10¹⁰ CFU/day for 8 weeks and showed an acute oral LD50 exceeding 2 × 10¹⁰ CFU/kg in mice. These findings support further investigation of LH76 in larger and more mechanistic studies.
Developing targeted cancer therapies with high selectivity, low toxicity, and cost-effectiveness remains a major challenge in modern medicine. This study aimed to design a Gallocin-derived anticancer peptide (ACP) targeting the epidermal growth factor receptor (EGFR) using an integrated bioinformatics and experimental approach. Gallocin, a bacteriocin from Streptococcus gallolyticus, was selected for its unique four α-helix structure and anticancer motifs, making it a promising candidate for ACP in initial in silico analysis. The Gallocin-derived ACPs were predicted using web-based tools. Molecular docking studies assessed the binding affinity of ACPs to EGFR, and molecular dynamics simulations analyzed the stability of the Galcn-1-EGFR complex. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis evaluated pharmacokinetic properties. Docking revealed that Galcn-1 had a high binding affinity for EGFR, forming stable hydrogen bonds. Molecular dynamics simulations confirmed complex stability. Experimental validation showed that Galcn-1 exhibited an IC₅₀ of 16 µg/ml in HT-29 cells. Galcn-1 downregulated EGFR and PI3K expression, induced apoptosis via both extrinsic (CAS-8) and intrinsic (CAS-9) pathways, increased ROS production, and caused cell cycle arrest in the S-phase. Pharmacokinetic evaluations indicated improved metabolism and lower toxicity, along with decreased permeability and a shorter half-life. Future optimization through bioengineering, such as peptide conjugation and chemical modifications (PEGylation), use of a synthetic staple, and development of drug delivery systems, will enhance stability, protect the peptide from proteolytic degradation, extend its half-life and binding affinity, and improve permeability and function, positioning Galcn-1 for further preclinical and clinical development.
This study aimed to characterize lactic acid bacteria (LAB) isolated from donkey milk and to evaluate the probiotic properties of selected strains. A total of 97 isolates collected over one year were identified by MALDI-TOF MS, revealing eight LAB species, predominantly Lacticaseibacillus paracasei and Lactiplantibacillus plantarum. Based on preliminary safety and functional screening, 22 L. paracasei and 11 L. plantarum strains were selected for further characterization. All isolates were γ-hemolytic and DNase-negative. The selected strains exhibited tolerance to acidic conditions (pH 2-3) and bile salts (up to 1%). Cell surface hydrophobicity was generally high among the isolates, while auto-aggregation and co-aggregation values ranged between 52.1 and 3.2% and - 39-47.9%, respectively, depending on the isolate. Exopolysaccharide (EPS) production ranged from 348.4 to 622.9 µg/mL glucose equivalents, and FTIR analysis indicated structural variability among the produced EPS samples. Antimicrobial activity against Staphylococcus aureus, Listeria monocytogenes, Escherichia coli O157:H7, and Salmonella spp. was detected in 6 of 22 L. paracasei isolates and 7 of 11 L. plantarum isolates. Neutralization assays indicated that the observed antimicrobial effects were primarily associated with organic acid production and low pH conditions. All isolates exhibited strong inhibition responses to ampicillin, whereas reduced inhibition responses to vancomycin were observed in some strains. Overall, donkey milk was identified as a potential source of LAB exhibiting probiotic-related functional characteristics. However, further molecular, MIC-based, and in vivo studies are required to confirm the safety and functional efficacy of these strains.
Atherosclerosis is a chronic inflammatory disease influenced by host-microbiota interactions beyond traditional risk factors. Microbial communities in the oral cavity, gut, and blood contribute to vascular dysfunction through metabolic and immune mechanisms, yet an integrated perspective across these compartments remains lacking. This narrative review synthesizes current evidence on the distinct and interconnected roles of oral, gut, and blood microbiotas in atherosclerosis pathogenesis. We critically evaluate key microbial metabolites, trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and secondary bile acids, and their mechanisms of host metabolic and immune modulation. We also examine cross-compartment interactions, emerging multi-omics approaches, and the translational potential of microbiota-targeted interventions. Oral pathogens promote systemic inflammation and endothelial activation. Gut-derived metabolites such as TMAO exacerbate foam cell formation and impair reverse cholesterol transport, whereas SCFAs exert protective effects via immune modulation and gut barrier maintenance. Emerging evidence suggests that blood microbial components contribute to vascular inflammation, though methodological challenges remain. Multi-omics integration (metagenomics, metabolomics, host genomics) reveals interconnected metabolic networks linking microbial activity to atherosclerosis. Microbiota-targeted strategies, including dietary modulation, TMA lyase inhibitors, and probiotics, show promise for risk stratification and therapeutic intervention. The human microbiota regulates atherosclerosis through immunometabolic metabolites, offering promising biomarkers and therapeutic targets. However, clinical translation requires addressing interindividual variability, establishing causality, and standardizing methodologies. This review provides an integrated framework for leveraging microbiota-host interactions in precision cardiovascular medicine.
Postbiotics are stable, non-living microbial products that provide health benefits similar to probiotics and have lower safety concerns. Despite the expanding recognition and use of postbiotics, little is known about the specific properties and applications of postbiotics derived from cold-active (psychrophilic or psychrotolerant) microbial strains. To identify the molecular mechanisms that underpin therapeutic applications, we isolated cold-active probiotic candidates at 4 °C from fermented foods (feta cheese and kefir) sourced from local markets. Cell-free supernatant (CFS) of the isolates was initially screened for antioxidant activity, then followed by assessment of antimicrobial effects against Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis. Cold-active Lactobacillus fuchuensis H.Y.35 showed strong antioxidant and antimicrobial capacities compared to other isolates. Antifreeze and cryoprotective assays confirmed that H.Y.35 postbiotics inhibited ice recrystallization and reduced drip loss in frozen cells. Untargeted metabolomics of H.Y.35 CFS identified bioactive compounds, including phenolic acids, fatty acyl derivatives, and amino acid-based metabolites. These bioactive compounds are linked to radical scavenging, antimicrobial activity, and cryoprotection. Complementary proteomic analysis further revealed the enrichment of proteins involved in stress adaptation, antimicrobial defense, and cryoprotection. These detected compound include pseudouridine synthase, cyclic-di-AMP phosphodiesterase, RNA polymerase sigma factor SigA, and the Sakacin Q immunity protein. These findings provide molecular evidence supporting the multifunctionality of cold-active postbiotics. The Lactobacillus fuchuensis H.Y.35 postbiotics/CFS also demonstrated potent wound-healing activity in vitro at 1% and 10% (v/v) concentrations, achieving up to 100% closure within 24 h (p < 0.01). This multifunctionality highlights the biotechnological and therapeutic potential of cold-active postbiotics as natural agents for health and industrial applications.
Following the 2020 ban on antibiotic growth promoters in animal feed, diarrheal disease in weaned rabbits has become an increasingly important challenge for the rabbit industry. Due to their superior intestinal adaptability and colonization potential, host-derived probiotics are considered promising alternatives. In this study, Limosilactobacillus fermentum RLF77, a lactic acid bacterium, was isolated from the intestinal contents of healthy young rabbits. Strain RLF77 showed a favorable safety profile, including γ hemolysis, a negative indole reaction, and no production of biogenic amines. Furthermore, the strain exhibited strong tolerance to heat, acidic conditions, bile salts, and simulated gastrointestinal fluids, as well as broad antimicrobial activity against a range of enteric pathogens. It also displayed moderate cell surface hydrophobicity, auto-aggregation ability, and strong antioxidant activity. Whole genome sequencing revealed that RLF77 possesses a 2.31 Mbp genome enriched in genes involved in carbohydrate and amino acid metabolism, stress response, and oxidative defense. In addition, genome mining identified biosynthetic gene clusters putatively encoding enterolysin A. Oral administration in mice further supported the in vivo safety of RLF77 and significantly increased villus height and the villus height/crypt depth ratio. In an E. coli-challenged weaned rabbit model, dietary RLF77 supplementation improved growth performance, reduced diarrhea incidence, enhanced immune and antioxidant capacity, alleviated intestinal injury, and improved gut microbiota composition by increasing microbial richness and Akkermansiaceae abundance. Collectively, the host-derived strain L. fermentum RLF77 is a safe and promising probiotic candidate for improving intestinal health and preventing post-weaning diarrhea in rabbits.