{"title":"Postbiotic Metabolites: Therapeutic Potential, Industrial Applications, Market Dynamics, and Regulatory Frameworks.","authors":"Atru Gnana Surya Chandu, Akula Venkata Nagarjuna, Abinaya Soundar, Siby Isac, Sahana Nedunchezhian, Gayathri Shama Bhat, Kavish Kumar Jain","doi":"10.1007/s12602-026-11213-5","DOIUrl":"https://doi.org/10.1007/s12602-026-11213-5","url":null,"abstract":"<p><p>Postbiotic metabolites, bioactive compounds produced by probiotic microorganisms, have emerged as key players in modulating host health. Despite extensive documentation of individual classes and their health benefits, there remains a lack of an integrated understanding linking specific metabolites to their mechanisms of action remains a primary research gap, this contributes to ongoing challenges in standardization, clinical validation and long-term efficacy studies that pose hurdles to widespread adoption. This review consolidates evidence on major postbiotic metabolites, including short-chain fatty acids, peptides, organic acids, bacteriocins, and extracellular vesicles, derived from probiotic genera such as Lactobacillus, Bifidobacterium, Pediococcus, and Saccharomyces. It characterizes their roles in maintaining gut barrier function, regulating immune responses, and influencing metabolic processes, with implications for metabolic disorders, immune-related conditions, neurodegenerative diseases, and skin health. Given their stability, safety, and efficacy, postbiotic-based formulations are gaining traction in the functional food and nutraceutical industries, leading to a surge in products ranging from dietary supplements, fermented foods, to pharmaceutical formulations. Overall, this analysis underscores the need for well-designed clinical studies, standardized regulatory guidelines, and interdisciplinary research to support the effective use of postbiotics in precision medicine and personalized nutrition.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148963522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unveiling the Gastric Microbiome: Novel Insights into Early Detection and Pathogenesis of Gastric Cancer.","authors":"Suresh Malchi, Kodiganti Naresh Kumar, Sreekanthyadav Pokala, Sathish Kumar Venkatachalam, Parthasarathy Ranganathan, Nallusamy Duraisamy","doi":"10.1007/s12602-026-11134-3","DOIUrl":"https://doi.org/10.1007/s12602-026-11134-3","url":null,"abstract":"<p><p>Gastric cancer (GC) remains a major global health burden and is frequently diagnosed at advanced stages owing to the limited sensitivity, invasiveness, and restricted availability of current screening strategies. Increasing evidence indicates that the gastric microbiome including Helicobacter pylori and diverse non-H. pylori bacteria, fungi, and viruses actively contribute to gastric carcinogenesis by modulating mucosal immunity, chronic inflammation, epithelial barrier integrity, and metabolism. High-throughput sequencing has revealed reproducible dysbiosis signatures in GC, characterized by enrichment of taxa such as Lactobacillus, Streptococcus, and Fusobacterium, and depletion of beneficial commensals, including Bifidobacterium and short-chain fatty acid producing anaerobes, some of which show promise as diagnostic or prognostic biomarkers. This review summarizes current knowledge on bacterial, fungal, and viral inhabitants of gastric tumors, highlighting their mechanistic roles in tumor initiation and progression and their potential as microbial indicators of disease. It further evaluates noninvasive and minimally invasive early detection strategies based on fecal and salivary microbiota profiling, urinary extracellular vesicles, and metabolomic fingerprints, alongside multi-omics integration and machine-learning models that combine microbial and host features to improve risk stratification. Finally, the review discusses therapeutic avenues including microbiota modulation, immunotherapy microbiome interactions, and personalized medicine frameworks that incorporate microbial signatures into clinical decision-making, underscoring the need for standardized, multicenter studies to translate gastric microbiome insights into robust tools for early detection and targeted intervention in GC.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Animal-Derived Antimicrobial Peptides: Emerging Therapeutic Strategies against Multidrug-Resistant Pathogens.","authors":"Mallu Mallikarjuna, Narasimha Golla","doi":"10.1007/s12602-026-11225-1","DOIUrl":"https://doi.org/10.1007/s12602-026-11225-1","url":null,"abstract":"<p><p>The global escalation of antimicrobial resistance (AMR) has outpaced the conventional antibiotic discovery pipeline, with bacterial AMR associated with an estimated 4.71 million deaths in 2021 and forecast to contribute to rising mortality through 2050. The World Health Organization's 2024 Bacterial Priority Pathogens List continues to identify carbapenem-resistant Gram-negative organisms and rifampicin-resistant Mycobacterium tuberculosis as the most urgent targets for new therapeutics. Antimicrobial peptides (AMPs), ancient and evolutionarily conserved effectors of innate immunity, are one of several candidate classes under active investigation. The animal kingdom, spanning mammals, amphibians, fish, insects, arachnids, and venomous taxa, is a structurally and functionally diverse reservoir of these molecules, and this diversity has already attracted several recent, more narrowly focused reviews covering venom-derived, marine-derived, and computationally designed AMPs. The present narrative review instead undertakes a cross-taxon comparative synthesis, explicitly distinguishing native animal peptides, proteolytic fragments of animal proteins, and synthetic analogues derived from an animal scaffold from the bacterial and fungal peptide antibiotics sometimes discussed alongside them. We survey the principal structural families and their taxonomic sources, compare their membrane-disruptive and intracellular mechanisms, and critically assess their anti-biofilm activity by distinguishing biofilm prevention from eradication of established biofilms. We examine the molecular determinants of bacterial resistance to AMPs with reference to the primary mechanistic literature, and we compile a verified, trial-identifier-referenced account of clinical development that separates candidates with completed Phase III evaluation from those with only preclinical or unverified clinical support. Every animal-derived AMP evaluated in a controlled human trial to date has either failed to demonstrate superiority over an existing comparator or remains restricted to topical or localised use; none has achieved new systemic regulatory approval. Against this evidence base, we argue that the realistic near-term contribution of animal-derived AMPs lies in combination therapy with existing antibiotics and in topical or localised indications with direct clinical evidence, while their use as stand-alone systemic agents remains a preclinical and early-clinical prospect rather than an established therapeutic reality.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149064249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elvina Parlindungan, Yifeng Wei, Naedia Xuan Yi Loh, Veronica Wee Pin Ng, John En Song Luah, Mario Wibowo
{"title":"Evaluation of Indigenous Bacillus Strains from Asian Fermented Foods for Probiotic Properties.","authors":"Elvina Parlindungan, Yifeng Wei, Naedia Xuan Yi Loh, Veronica Wee Pin Ng, John En Song Luah, Mario Wibowo","doi":"10.1007/s12602-026-11210-8","DOIUrl":"https://doi.org/10.1007/s12602-026-11210-8","url":null,"abstract":"<p><p>Bacillus species hold particular importance due to their versatile enzymatic repertoire and ability to synthesize diverse bioactive metabolites. In this study, two fermented food-derived strains, Bacillus siamensis BB3 (from douchi) and Bacillus velezensis TMA10 (from tapai) were evaluated for their probiotic, anti-microbial and functional potentials. Both strains exhibited desirable probiotic characteristics, including desirable tolerance to simulated gastric and intestinal conditions, with BB3 showing greater acid tolerance than TMA10. Safety assessments confirmed the absence of hemolytic activity, virulence factors and antibiotic resistance genes. Whole genome sequencing showed that the strains harbored genomic sequences for a wide range of metabolites, including non-ribosomal peptides and polyketides. Ethyl acetate (EtOAc) extracts from both strains demonstrated broad-spectrum anti-microbial activity against several indicator microorganisms, including Listeria grayi, Bacillus cereus, Serratia marcescens, Escherichia coli, and Pseudomonas aeruginosa, with TMA10 additionally inhibiting MRSA and Streptococcus mutans. Liquid Chromatography-Mass Spectrometry profiling identified key anti-microbial compounds, namely surfactins, macrolactins, bacillaene from BB3 and TMA10. In addition, difficidins were also detected from TMA10. Genomic analysis further indicated diverse carbohydrate utilization capacities; both strains encoded pathways for sucrose, raffinose-family oligosaccharides and lactose metabolism, while TMA10 possessed pathways for trehalose, glucomannan and arabinoxylan degradation. Both strains also showed anti-oxidant activity, with enhanced effects observed in their cell-free supernatants and heat-killed preparations. Overall, these findings highlight BB3 and TMA10 as promising candidates for the development of fermented food-derived Bacillus probiotics and functional cultures with anti-microbial, anti-oxidant, and broad carbohydrate-utilization capabilities.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Carolina Nascimento Cidrini Golo, Thaís Emanuelle Silva Santos, Fernanda Teixeira Santos, Lara Beatriz Oliveira Mateus, Isabella Maciel Costa, Taynan Jonatha Neves Costa, Vinicius Tadeu da Veiga Correia, Erika Ramos Alvarenga, Luciano Soares de Lima, Henrique César Pereira Figueiredo, Elisabeth Neumann, Bruna Maria Salotti de Souza
{"title":"Indigenous Fruit-Derived Lactic Acid Bacteria with Probiotic Potential and Angiotensin-Converting Enzyme I Inhibitory Activity.","authors":"Ana Carolina Nascimento Cidrini Golo, Thaís Emanuelle Silva Santos, Fernanda Teixeira Santos, Lara Beatriz Oliveira Mateus, Isabella Maciel Costa, Taynan Jonatha Neves Costa, Vinicius Tadeu da Veiga Correia, Erika Ramos Alvarenga, Luciano Soares de Lima, Henrique César Pereira Figueiredo, Elisabeth Neumann, Bruna Maria Salotti de Souza","doi":"10.1007/s12602-026-11212-6","DOIUrl":"https://doi.org/10.1007/s12602-026-11212-6","url":null,"abstract":"<p><p>The prospecting of lactic acid bacteria (LAB) from natural niches represents a strategy in the development of functional foods. Fruits are promising sources of LAB adapted to acidic environments. This study evaluated the probiotic and biotechnological potential of LAB isolated from native fruits of the Minas Gerais biomes. Thirteen strains were isolated from pequi (Caryocar brasiliense) and tree tomato (Solanum betaceum), identified as Leuconostoc mesenteroides (MQ389, MQ395, MQ396, MQ397, MQ398, and MQ402), Weissella cibaria (MQ391 and MQ404), Pediococcus pentosaceus (MQ392 and MQ390), Enterococcus faecalis (MQ403), Lacticaseibacillus paracasei (MQ393), and Lactiplantibacillus plantarum (MQ394). Nine LAB showed γ-hemolysis. When evaluating susceptibility to antimicrobials, all strains were susceptible to chloramphenicol. MQ391 was susceptible to all nine tested antimicrobials. MQ393 showed autoaggregation of 26.37% at 37 °C and coaggregation greater than 81% with E. coli. Hydrophobicity results did not exceed 7.49% (MQ390). Seven LAB maintained counts above 8.0 log CFU/mL after simulated gastrointestinal conditions. Only MQ402 exhibited moderate antagonistic activity against Staphylococcus aureus. The tested LAB demonstrated technological potential through the production of exopolysaccharides and β-galactosidase, proteolytic activity, and absence of gelatinase. The evaluated strains showed promising functional characteristics, with ACE-I inhibitory activity observed above 80% across the strains and BSH activity qualitatively detected in seven of the nine strains (77.78%). Indigenous LAB from fruits of the Minas Gerais biome show promising properties for application in fermented foods.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Asiya Batool, Hussain Ali, Usman Waheed, Muhammad Nadeem Hassan
{"title":"Genomic Insights Into the Probiotic and Safety Attributes of Pediococcus acidilactici BC-7 for its Potential Application in Livestock Health.","authors":"Asiya Batool, Hussain Ali, Usman Waheed, Muhammad Nadeem Hassan","doi":"10.1007/s12602-026-11208-2","DOIUrl":"https://doi.org/10.1007/s12602-026-11208-2","url":null,"abstract":"<p><p>Pediococcus acidilactici is widely recognized for its health-beneficial aspects and has gained increasing interest for use in livestock industry. It shows strong probiotic efficacy, antimicrobial activity, cholesterol-lowering potential, immune modulation, and other therapeutic attributes. The novel strain from indigenous habitats mainly depicted potent probiotic efficacy and high adaptability. In this study, we evaluated the probiotic characteristics and genomic features of strain BC-7 obtained from a Nili - Ravi buffalo calf raised under domestic conditions using phenotypic assessment, genomic analysis and in vivo studies. The strain BC-7 exhibited key probiotic traits i.e., gut tolerance (70.43% - 97.5%), auto-aggregation (85.24%), co-aggregation (14.33% - 25.88%), hydrophobicity (78.33% - 88%), antioxidant potential (54%), and antibacterial activity (16.47-18 mm). The safety analysis revealed that BC-7 exhibited susceptibility and resistance to various antimicrobial agents and showed no β hemolytic activity. BC-7 was taxonomically classified as Pediococcus acidilactici by 16 S rRNA gene sequencing. Whole genome sequence (WGS) analysis showed that P. acidilactici BC-7 contains a 1.9 Mb genome with 42% GC content. Pediococccus acidilactici BC-7 harbored 1900 genes, which were mainly associated with metabolism and genetic processes. Based on genomic comparison, BC-7 shared 99% average nucleotide identity and strong genomic collinearity with P. acidilactici NARCC1 which is a TYPE strain having potent probiotic potential. Probiotic strain BC-7 shared 1,664 core genes with reference strains and 69 unique genes specific for metabolism and genetic processes. The BC-7 strain contained unique bacteriocins-associated genes and defense-related CAzymes, it harbors only vancomycin resistance genes and lacked true virulence determinants. In vivo trial showed that BC-7 treated mice showed increased growth rate, improved immune modulation, and membrane integrity. These significant findings revealed that BC-7 emerging as a potential probiotic strain with strong functionality and efficacy. Thus, our strain BC-7 could be used as a promising candidate for applications in the animal health industry.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unravelling Probiotic-Associated Traits and Protective Efficacy of Limosilactobacillus fermentum Strains Against Colitis.","authors":"Moubonny Das, Pinaki Biswas, Raktim Ghosh, Anirban Nandi, Raju Biswas, Tarun Kumar Kar, Sandip Chattopadhyay, Somasri Dam","doi":"10.1007/s12602-026-11211-7","DOIUrl":"https://doi.org/10.1007/s12602-026-11211-7","url":null,"abstract":"<p><p>Colitis is a serious gastrointestinal disorder, and drug therapy has problems of recurrence upon withdrawal as well as adverse effects from prolonged usage. Therefore, probiotics can be an effective substitute. This study aims to isolate bacterial strains having probiotic attributes and defensive traits against colitis. Initially, forty strains were isolated from Haria, a traditional rice-based fermented beverage of West Bengal, India. Eight isolates were selected based on their acid and bile salt tolerance properties. These selected isolates showed anti-amoebic activity against Entamoeba histolytica, a human protozoan parasite that causes colitis, amoebiasis and other disorders. Subsequently, the isolates were identified as Limosilactobacillus fermentum by 16S rRNA gene sequence analysis. Their phenotypic probiotic attributes, such as GI survival rate, good adhesion, antioxidant activity, inhibitory activity against four pathogenic bacterial strains, and safety evaluation, identified two promising strains, L-31 and L-35. They were further used as a probiotic mixture and ameliorated dextran sulfate sodium-induced colitis in experimental mice by protecting colon length and body weight loss, restoring organ indices, decreasing disease activity index score, improving blood parameters, reducing coliform count, and repairing tissues. L-31 has been identified as a promising candidate with good probiotic potential and protective effects against colitis, but further studies on its safety, efficacy, stability, formulation suitability, and clinical applicability are necessary for potential therapeutic applications.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Safety Assessment on Probiotic Mixture \"Prohep\" and Longitudinal Evaluation on its Gut Microbial Modulation Ability in Mice.","authors":"Fangfei Zhang, Koei Ho Lam Cheung, Emily Kwun Kwan Lo, Congjia Chen, Jetty Chung-Yung Lee, Felicianna, Marsena Jasiel Ismaiah, Hoi Kit Matthew Leung, Hani El-Nezami","doi":"10.1007/s12602-026-11209-1","DOIUrl":"https://doi.org/10.1007/s12602-026-11209-1","url":null,"abstract":"<p><p>The probiotic mixture Prohep has been studied as a potential therapy for liver diseases such as MASLD, MASH, and HCC. To evaluate its safety, we conducted an experiment on CD-1 mice to assess its acute, subacute, and subchronic oral toxicity. The results showed that Prohep intake did not cause any morbidity or mortality, nor did it produce adverse changes in body weight, histopathological, haematological, or biochemical parameters. Therefore, Prohep is considered safe for consumption, with LD<sub>50</sub> of Prohep being higher than 5000 mg/kg (category 5, LD<sub>50</sub> > 2000 mg/kg) and no-observed-adverse-effect-level (NOAEL) of Prohep being 2800 mg/kg. Furthermore, we investigated the ability of Prohep to modulate gut microbiota under both normal chow and high-fat diets. Based on faecal DNA sequencing results, a continuous 28-day course of Prohep supplementation is required to achieve complete reshaping of the gut microbiota composition. This 28-day supplementation window may therefore be informative for designing human dosing regimens aimed at inducing durable, clinically meaningful modulation of the gut microbiota. The modulatory effects of Prohep supplementation on gut microbiota were still observed 28 days after withdrawal. These findings provide valuable information for the pharmaceutical use of Prohep, including its safety and optimal duration of probiotic supplementation.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christian Kosisochukwu Anumudu, Chijioke Christopher Uhegwu, Teyfik Çelen
{"title":"Harnessing Probiotic LAB and Bacteriocins for Clean-Label Food Processing and Biopreservation: Omics, Molecular Innovations and Industrial Applications.","authors":"Christian Kosisochukwu Anumudu, Chijioke Christopher Uhegwu, Teyfik Çelen","doi":"10.1007/s12602-026-11201-9","DOIUrl":"https://doi.org/10.1007/s12602-026-11201-9","url":null,"abstract":"<p><p>The persistence of microbial agents in foods, especially spore forming bacteria is one of the most significant challenges to food preservation and safety, undermining product quality, shelf life, and consumer health. The use of traditional control methods, including thermal processing and chemical preservatives, are increasingly limited by consumer demands for minimally processed foods, and the emergence of resistant microbial strains. Advances have been made in the use of probiotics like lactic acid bacteria (LAB) and their biometabolites like bacteriocins in food processing and preservation, particularly to control biofilm and endospore forming pathogens including Bacillus sp., Listeria sp., Staphylococcus sp., Clostridium sp., E. coli etc. in foods and food processing plants/surfaces. Given the ability of these organisms to cause foodborne illness and form resilient biofilms in the food processing ecosystem and their resistance to the conventional method of their elimination, the antimicrobial peptides (bacteriocins) are gaining increasing prominence as useful alternatives to synthetic antimicrobials in enhancing food safety and combating the threats of these pathogens. This review addresses current information on the inhibition of persistent microbial spoilage contaminants, biofilm-forming pathogens, and spore formers of interest to the food industry using LAB and their bacteriocins. Current developments in isolation, characterization, and mode of action of bacteriocins are explored, including synergistic activity with other preservative hurdle techniques such as encapsulation, and nanobiotechnology. Importantly, there is a focus on the utilization of molecular and omics-based approaches to enable a better understanding of bacteriocin biosynthesis, gene regulation, host-microbe interactions and gut microbiome regulation potential of probiotic LABs, permitting the rational development of targeted and strain-specific interventions. Developments in the incorporation of bacteriocin-producing LAB into functional starter cultures and bio-protective products, and challenges in stability, regulatory approval, and scalability for industrial use, are also discussed in the paper. Despite their considerable potential, broader translation remains constrained by regulatory requirements, production and formulation costs, variable efficacy in complex food matrices, and the limited validation of many candidate bacteriocins beyond laboratory and model-food systems. Collectively, these advances position LAB and their bacteriocins at the leading edge of developing sustainable, clean-label, and efficacious functional foods and food preservation systems. Their functionality can be expanded by integrating genomics, synthetic biology, and predictive modeling for the maximization of their biopreservative potential in diverse food matrices and in gut microbiota modulation.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Della Grace Thomas Parambi, Prabhakaran Prabitha, Tariq G Alsahli, Arafa Musa, Dibya Sundar Panda, Dipen Purohit, Raja Karukuvelraja, Manal Mohammed
{"title":"Rational Design and In Silico Evaluation of a Dual-Action Antimicrobial Peptide Targeting Efflux Pump and Membrane Integrity in Pseudomonas aeruginosa.","authors":"Della Grace Thomas Parambi, Prabhakaran Prabitha, Tariq G Alsahli, Arafa Musa, Dibya Sundar Panda, Dipen Purohit, Raja Karukuvelraja, Manal Mohammed","doi":"10.1007/s12602-026-11192-7","DOIUrl":"https://doi.org/10.1007/s12602-026-11192-7","url":null,"abstract":"<p><p>The increasing prevalence of multidrug-resistant (MDR) Pseudomonas aeruginosa, largely associated with overexpression of the MexAB-OprM efflux pump, highlights the need for alternative antimicrobial strategies. In this study, antimicrobial peptide (AMP) candidates were rationally designed using the Artificial Neural Network (ANN) and Random Forest (RF) models implemented in the CAMPR4 platform. Approximately 18,000 AMP sequences were screened, resulting in nine candidate peptides that were subsequently evaluated for physicochemical properties, predicted hemolytic activity, and antimicrobial potential using the dbAMP framework. Five non-hemolytic peptides (1ANN, 2ANN, 4RF, 5RF, and 6RF) were selected for further analysis based on their predicted physicochemical characteristics and antimicrobial profiles. Molecular docking against the three components of the MexAB-OprM efflux pump (MexA, MexB, and OprM) predicted binding affinities ranging from - 7.1 to - 14.1 kcal mol⁻¹. Among the evaluated peptides, 2ANN was the only peptide predicted to form a hydrogen bond between Lys15 and Asp61 of MexA. Molecular dynamics simulations demonstrated that the 2ANN-MexA complex remained structurally stable over 200 ns, while membrane simulations showed spontaneous adsorption of 2ANN onto a Gram-negative membrane and persistent membrane association throughout the simulation. Collectively, these computational analyses identified 2ANN as a promising AMP candidate for further investigation against MDR P. aeruginosa. However, as the findings are based exclusively on computational prediction and simulation, experimental validation, including peptide synthesis, antimicrobial susceptibility testing, hemolytic assays, and efflux pump inhibition studies, is required to confirm its biological activity and mechanism of action.</p>","PeriodicalId":20506,"journal":{"name":"Probiotics and Antimicrobial Proteins","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}