{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:39:58Z","timestamp":1792460398685,"version":"4.5.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Microbiota-targeted strategies are increasingly moving beyond the administration of live microorganisms toward cell-free microbial components with postbiotic potential. Among these, extracellular vesicles released by lactic acid bacteria (LAB-derived EVs) are emerging as biologically active particles capable of transferring bacterial signals to host epithelial and immune cells. However, their effects should not be interpreted as uniform or intrinsically beneficial, because vesicle composition and activity are strongly influenced by bacterial strain, culture conditions, growth phase, isolation procedures and target cell context. In this Perspective, we discuss LAB-derived EVs as candidate postbiotic modulators of epithelial adhesion and barrier homeostasis. We focus on the epithelial interface as an integrated functional unit in which tight junctions, adherens junctions, junctional adhesion molecules, integrin-related cell\u2013matrix adhesion, extracellular matrix remodeling and epithelial\u2013immune communication converge. Evidence, largely derived from\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    \/\n                    <jats:italic>Lactobacillaceae<\/jats:italic>\n                    models, supports the ability of LAB-derived EVs to influence barrier integrity, inflammatory tone, pathogen adhesion and tissue repair. We also propose an exploratory framework based on early transcriptional responses observed in A549 respiratory epithelial cells exposed to an EV-enriched preparation obtained from\n                    <jats:italic>Lactobacillus fermentum<\/jats:italic>\n                    18A-TV, highlighting a transcriptional signature compatible with transient epithelial remodeling involving junctional, extracellular matrix, integrin-related and repair-associated genes. Future studies should combine standardized EV characterization with protein-level and functional assays to define reproducible potency markers and clarify the therapeutic potential of LAB-derived EVs.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1905504","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T06:01:53Z","timestamp":1785304913000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Lactic acid bacteria-derived extracellular vesicles as postbiotic modulators of epithelial adhesion and barrier homeostasis: emerging perspectives"],"prefix":"10.3389","volume":"17","author":[{"given":"Francesco","family":"Coppolino","sequence":"first","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \"Gaetano Barresi\", University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Tavella","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \"Gaetano Barresi\", University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Berbiglia","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \"Gaetano Barresi\", University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco Simone","family":"Sframeli","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \"Gaetano Barresi\", University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Filippone","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \"Gaetano Barresi\", University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Grasso","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \"Gaetano Barresi\", University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Fam\u00e0","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \"Gaetano Barresi\", University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta Lucia","family":"Pecora","sequence":"additional","affiliation":[{"name":"Section Microbiology, Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania","place":["Catania, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Santagati","sequence":"additional","affiliation":[{"name":"Section Microbiology, Department of Biomedical and Biotechnological Sciences (BIOMETEC), University of Catania","place":["Catania, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Germana","family":"Lentini","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \"Gaetano Barresi\", University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe Valerio","family":"De Gaetano","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \"Gaetano Barresi\", University of Messina","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Beninati","sequence":"additional","affiliation":[{"name":"Department of Human Pathology in Adult and Developmental Age \"Gaetano Barresi\", University of Messina","place":["Messina, Italy"]},{"name":"Scylla Biotech Srl","place":["Messina, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1007\/978-3-031-62036-2_19","article-title":"Microbial extracellular vesicles in host-microbiota interactions","volume":"73","author":"Abubaker","year":"2024","journal-title":"Results Probl. Cell Differ."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/s12551-013-0124-0","article-title":"Structural and mechanical functions of integrins","volume":"6","author":"Anderson","year":"2014","journal-title":"Biophys. Rev."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"19237","DOI":"10.1038\/s41598-020-75930-9","article-title":"Lactobacillus casei extracellular vesicles stimulate EGFR pathway likely due to the presence of proteins P40 and P75 bound to their surface","volume":"10","author":"B\u00e4uerl","year":"2020","journal-title":"Sci. Rep."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e00433-20","DOI":"10.1128\/IAI.00433-20","article-title":"Extracellular vesicle biogenesis and functions in gram-positive bacteria","volume":"88","author":"Briaud","year":"2020","journal-title":"Infect. Immun."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1038\/nrmicro3480","article-title":"Through the wall: extracellular vesicles in gram-positive bacteria, mycobacteria and fungi","volume":"13","author":"Brown","year":"2015","journal-title":"Nat. Rev. Microbiol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"a029314","DOI":"10.1101\/cshperspect.a029314","article-title":"Cell biology of tight junction barrier regulation and mucosal disease","volume":"10","author":"Buckley","year":"2018","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/s12276-019-0359-3","article-title":"Lactobacillus paracasei-derived extracellular vesicles attenuate the intestinal inflammatory response by augmenting the endoplasmic reticulum stress pathway","volume":"52","author":"Choi","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1186\/s12934-022-01963-6","article-title":"Lactobacilli extracellular vesicles: potential postbiotics to support the vaginal microbiota homeostasis","volume":"21","author":"Croatti","year":"2022","journal-title":"Microb. Cell Factories"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1479","DOI":"10.1111\/mmi.14920","article-title":"Streptococcus pneumoniae binds collagens and C1q via the SSURE repeats of the PfbB adhesin","volume":"117","author":"De Gaetano","year":"2022","journal-title":"Mol. Microbiol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1367898","DOI":"10.3389\/fmicb.2024.1367898","article-title":"Engagement of \u03b13\u03b21 and \u03b12\u03b21 integrins by hypervirulent Streptococcus agalactiae in invasion of polarized enterocytes","volume":"15","author":"De Gaetano","year":"2024","journal-title":"Front. Microbiol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1038\/s41598-018-37120-6","article-title":"Isolation and characterization of Lactobacillus-derived membrane vesicles","volume":"9","author":"Dean","year":"2019","journal-title":"Sci. Rep."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1006\/excr.1998.4172","article-title":"Characterization of the A549 cell line as a type II pulmonary epithelial cell model for drug metabolism","volume":"243","author":"Foster","year":"1998","journal-title":"Exp. Cell Res."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1242\/jcs.193482","article-title":"The mucosal barrier at a glance","volume":"130","author":"France","year":"2017","journal-title":"J. Cell Sci."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1459213","DOI":"10.3389\/fimmu.2024.1459213","article-title":"Extracellular vesicles from a novel Lactiplantibacillus plantarum strain suppress inflammation and promote M2 macrophage polarization","volume":"15","author":"Gong","year":"2024","journal-title":"Front. Immunol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"5296","DOI":"10.3390\/nu14245296","article-title":"Novel horizons in postbiotics: Lactobacillaceae extracellular vesicles and their applications in health and disease","volume":"14","author":"Gonz\u00e1lez-Lozano","year":"2022","journal-title":"Nutrients"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"777147","DOI":"10.3389\/fimmu.2021.777147","article-title":"Effect of extracellular vesicles derived from Lactobacillus plantarum Q7 on gut microbiota and ulcerative colitis in mice","volume":"12","author":"Hao","year":"2021","journal-title":"Front. Immunol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"522","DOI":"10.3390\/biomedicines8110522","article-title":"Extracellular vesicles derived from kefir grain Lactobacillus ameliorate intestinal inflammation via regulation of proinflammatory pathway and tight junction integrity","volume":"8","author":"Kang","year":"2020","journal-title":"Biomedicine"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"516","DOI":"10.4168\/aair.2018.10.5.516","article-title":"Lactobacillus plantarum-derived extracellular vesicles protect atopic dermatitis induced by Staphylococcus aureus-derived extracellular vesicles","volume":"10","author":"Kim","year":"2018","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1793514","DOI":"10.1080\/20013078.2020.1793514","article-title":"Lactobacillus plantarum-derived extracellular vesicles induce anti-inflammatory M2 macrophage polarization in vitro","volume":"9","author":"Kim","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"522","DOI":"10.3390\/pharmaceutics15020522","article-title":"Extracellular vesicles of probiotics: shedding light on the biological activity and future applications","volume":"15","author":"Krzy\u017cek","year":"2023","journal-title":"Pharmaceutics"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"136685","DOI":"10.1016\/j.foodchem.2023.136685","article-title":"Proteomic characterization of extracellular vesicles derived from lactic acid bacteria","volume":"427","author":"Lee","year":"2023","journal-title":"Food Chem."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"2427311","DOI":"10.1080\/19490976.2024.2427311","article-title":"Lactic acid bacteria derived extracellular vesicles: emerging bioactive nanoparticles in modulating host health","volume":"16","author":"Li","year":"2024","journal-title":"Gut Microbes"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1111\/1751-7915.13972","article-title":"Extracellular vesicle formation in Lactococcus lactis is stimulated by prophage-encoded holin-lysin system","volume":"15","author":"Liu","year":"2022","journal-title":"Microb. Biotechnol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"26913","DOI":"10.3402\/jev.v3.26913","article-title":"Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles","volume":"3","author":"L\u00f6tvall","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"5656","DOI":"10.1038\/s41467-019-13468-9","article-title":"Extracellular vesicles from symbiotic vaginal lactobacilli inhibit HIV-1 infection of human tissues","volume":"10","author":"\u00d1ahui Palomino","year":"2019","journal-title":"Nat. Commun."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"27263","DOI":"10.1038\/s41598-025-12873-z","article-title":"Comparative and pharmacological investigation of bEVs from eight Lactobacillales strains","volume":"15","author":"Park","year":"2025","journal-title":"Sci. Rep."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/s41575-021-00440-6","article-title":"The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics","volume":"18","author":"Salminen","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines","volume":"7","author":"Th\u00e9ry","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"3319","DOI":"10.3390\/nu13103319","article-title":"Lactobacillus rhamnosus GG derived extracellular vesicles modulate gut microbiota and attenuate inflammatory in DSS-induced colitis mice","volume":"13","author":"Tong","year":"2021","journal-title":"Nutrients"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"RESEARCH0034","DOI":"10.1186\/gb-2002-3-7-research0034","article-title":"Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes","volume":"3","author":"Vandesompele","year":"2002","journal-title":"Genome Biol."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1186\/s12951-024-02893-8","article-title":"Lactobacillus rhamnosus GG-derived extracellular vesicles promote wound healing via miR-21-5p-mediated re-epithelization and angiogenesis","volume":"22","author":"Wang","year":"2024","journal-title":"J. Nanobiotechnol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"e12404","DOI":"10.1002\/jev2.12404","article-title":"Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches","volume":"13","author":"Welsh","year":"2024","journal-title":"J. Extracell. Vesicles"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1273813","DOI":"10.3389\/fcimb.2023.1273813","article-title":"An update on our understanding of gram-positive bacterial membrane vesicles: discovery, functions, and applications","volume":"13","author":"Xu","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"2782","DOI":"10.1099\/ijsem.0.004107","article-title":"A taxonomic note on the genus Lactobacillus: description of 23 novel genera, emended description of the genus Lactobacillus Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae","volume":"70","author":"Zheng","year":"2020","journal-title":"Int. J. Syst. Evol. 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