REFERENCES
1. Zhang R, Li G, Wu Y, Wang X, Luan Q. Pathogenic mechanisms and potential applications of extracellular vesicles from periodontal pathogens in periodontitis. Front Immunol. 2024;15:1513983.
2. Gill S, Catchpole R, Forterre P. Extracellular membrane vesicles in the three domains of life and beyond. FEMS Microbiol Rev. 2019;43:273-303.
3. Di Naro M, Petronio Petronio G, Mukhtar F, et al. Extracellular vesicles in bacteria, archaea, and eukaryotes: mechanisms of inter-kingdom communication and clinical implications. Microorganisms. 2025;13:636.
4. Toyofuku M, Tashiro Y, Hasegawa Y, Kurosawa M, Nomura N. Bacterial membrane vesicles, an overlooked environmental colloid: biology, environmental perspectives and applications. Adv Colloid Interface Sci. 2015;226:65-77.
5. Toyofuku M, Schild S, Kaparakis-Liaskos M, Eberl L. Composition and functions of bacterial membrane vesicles. Nat Rev Microbiol. 2023;21:415-30.
6. Brown L, Wolf JM, Prados-Rosales R, Casadevall A. Through the wall: extracellular vesicles in Gram-positive bacteria, mycobacteria and fungi. Nat Rev Microbiol. 2015;13:620-30.
7. Mashburn-Warren L, McLean RJ, Whiteley M. Gram-negative outer membrane vesicles: beyond the cell surface. Geobiol. 2008;6:214-9.
8. Bose S, Aggarwal S, Singh DV, Acharya N. Extracellular vesicles: an emerging platform in gram-positive bacteria. Microb Cell. 2020;7:312-22.
9. Morishita M, Sagayama R, Yamawaki Y, Yamaguchi M, Katsumi H, Yamamoto A. Activation of host immune cells by probiotic-derived extracellular vesicles via TLR2-mediated signaling pathways. Biol Pharm Bull. 2022;45:354-9.
10. Chen X, Li Q, Xie J, Nie S. Immunomodulatory effects of probiotic-derived extracellular vesicles: opportunities and challenges. J Agric Food Chem. 2024;72:19259-73.
11. Li Z, Li M, Fang X, Yu D, Hu X. Dietary Lactobacillus johnsonii-derived extracellular vesicles ameliorate acute colitis by regulating gut microbiota and maintaining intestinal barrier homeostasis. Food Funct. 2024;15:11757-79.
12. Rima M, Dakramanji M, El Hayek E, El Khoury T, Fajloun Z, Rima M. Unveiling the wonders of bacteria-derived extracellular vesicles: from fundamental functions to beneficial applications. Heliyon. 2025;11:e42509.
13. Lima S, Matinha-Cardoso J, Tamagnini P, Oliveira P. Extracellular vesicles: an overlooked secretion system in cyanobacteria. Life. 2020;10:129.
14. Bril’kov MS, Stenbakk V, Jakubec M, et al. Bacterial extracellular vesicles: towards realistic models for bacterial membranes in molecular interaction studies by surface plasmon resonance. Front Mol Biosci. 2023;10:1277963.
15. Díaz-Garrido N, Badia J, Baldomà L. Microbiota-derived extracellular vesicles in interkingdom communication in the gut. J Extracell Vesicles. 2021;10:e12161.
16. Welsh JA, Goberdhan DCI, O’Driscoll L, et al.; MISEV Consortium. Minimal information for studies of extracellular vesicles (MISEV2023): from basic to advanced approaches. J Extracell Vesicles. 2024;13:e12404.
17. Ahmadi Badi S, Moshiri A, Fateh A, et al. Microbiota-derived extracellular vesicles as new systemic regulators. Front Microbiol. 2017;8:1610.
18. Xiu L, Wu Y, Lin G, Zhang Y, Huang L. Bacterial membrane vesicles: orchestrators of interkingdom interactions in microbial communities for environmental adaptation and pathogenic dynamics. Front Immunol. 2024;15:1371317.
19. Zhang Y, Song M, Fan J, Guo X, Tao S. Impact of probiotics-derived extracellular vesicles on livestock gut barrier function. J Anim Sci Biotechnol. 2024;15:149.
20. Wu Q, Kan J, Fu C, et al. Insights into the unique roles of extracellular vesicles for gut health modulation: mechanisms, challenges, and perspectives. Curr Res Microb Sci. 2024;7:100301.
21. O’Donoghue EJ, Krachler AM. Mechanisms of outer membrane vesicle entry into host cells. Cell Microbiol. 2016;18:1508-17.
22. Kaparakis-Liaskos M, Ferrero RL. Immune modulation by bacterial outer membrane vesicles. Nat Rev Immunol. 2015;15:375-87.
23. Chen S, Lei Q, Zou X, Ma D. The role and mechanisms of gram-negative bacterial outer membrane vesicles in inflammatory diseases. Front Immunol. 2023;14:1157813.
24. Kaparakis M, Turnbull L, Carneiro L, et al. Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells. Cell Microbiol. 2010;12:372-85.
25. Wang X, Eagen WJ, Lee JC. Orchestration of human macrophage NLRP3 inflammasome activation by Staphylococcus aureus extracellular vesicles. Proc Natl Acad Sci U S A. 2020;117:3174-84.
26. Deo P, Chow SH, Han ML, et al. Mitochondrial dysfunction caused by outer membrane vesicles from Gram-negative bacteria activates intrinsic apoptosis and inflammation. Nat Microbiol. 2020;5:1418-27.
27. Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2:17023.
28. Chen Z, Larregina AT, Morelli AE. Impact of extracellular vesicles on innate immunity. Curr Opin Organ Transplant. 2019;24:670-8.
29. Rodovalho VR, da Luz BSR, Rabah H, et al. Extracellular vesicles produced by the probiotic Propionibacterium freudenreichii CIRM-BIA 129 mitigate inflammation by modulating the NF-κB pathway. Front Microbiol. 2020;11:1544.
30. Melo-Marques I, Cardoso SM, Empadinhas N. Bacterial extracellular vesicles at the interface of gut microbiota and immunity. Gut Microbes. 2024;16:2396494.
31. Alvarez CS, Badia J, Bosch M, Giménez R, Baldomà L. Outer membrane vesicles and soluble factors released by probiotic Escherichia coli nissle 1917 and commensal ECOR63 enhance barrier function by regulating expression of tight junction proteins in intestinal epithelial cells. Front Microbiol. 2016;7:1981.
32. Lee HJ. Microbe-host communication by small RNAs in extracellular vesicles: vehicles for transkingdom RNA transportation. Int J Mol Sci. 2019;20:1487.
33. Kim HJ, Kim YS, Kim KH, et al. The microbiome of the lung and its extracellular vesicles in nonsmokers, healthy smokers and COPD patients. Exp Mol Med. 2017;49:e316.
34. Kageyama T, Ito T, Tanaka S, Nakajima H. Physiological and immunological barriers in the lung. Semin Immunopathol. 2024;45:533-47.
35. Lloyd CM, Marsland BJ. Lung homeostasis: influence of age, microbes, and the immune system. Immunity. 2017;46:549-61.
36. Dickson RP, Erb-Downward JR, Martinez FJ, Huffnagle GB. The microbiome and the respiratory tract. Annu Rev Physiol. 2016;78:481-504.
37. Man WH, de Steenhuijsen Piters WA, Bogaert D. The microbiota of the respiratory tract: gatekeeper to respiratory health. Nat Rev Microbiol. 2017;15:259-70.
38. O’Dwyer DN, Dickson RP, Moore BB. The lung microbiome, immunity, and the pathogenesis of chronic lung disease. J Immunol. 2016;196:4839-47.
39. Shen Y, Giardino Torchia ML, Lawson GW, Karp CL, Ashwell JD, Mazmanian SK. Outer membrane vesicles of a human commensal mediate immune regulation and disease protection. Cell Host Microbe. 2012;12:509-20.
40. Keshavarz Aziziraftar S, Bahrami R, Hashemi D, et al. The beneficial effects of Akkermansia muciniphila and its derivatives on pulmonary fibrosis. Biomed Pharmacother. 2024;180:117571.
41. Fadaee M, Mahrooghi D, Lahouty M, Oskouei SA, Nezhadi J. Postbiotics and extracellular vesicles: mechanisms of action and clinical promise in respiratory infections and inflammation. Infect Genet Evol. 2025;135:105837.
42. Bisaccia P, Zaramella A, Hochuli AHD, et al. Overview of extracellular vesicles as biomarkers and therapeutic tools in pediatric diseases: focus on the gut-lung axis. Extracell Vesicles Circ Nucl Acids. 2025;6:921-36.
43. Albano GD, Taverna S. From microbiota to cancer: role of extracellular vesicles in gut-lung axis. Cancers. 2025;17:3946.
44. Cordaillat-Simmons M, Rouanet A, Pot B. Live biotherapeutic products: the importance of a defined regulatory framework. Exp Mol Med. 2020;52:1397-406.
46. Macia L, Nanan R, Hosseini-Beheshti E, Grau GE. Host- and microbiota-derived extracellular vesicles, immune function, and disease development. Int J Mol Sci. 2019;21:107.
47. Krzyżek P, Marinacci B, Vitale I, Grande R. Extracellular vesicles of probiotics: shedding light on the biological activity and future applications. Pharmaceutics. 2023;15:522.
48. Raja M, Ramamurthy K, Sudhakaran G, Guru A, Arockiaraj J. Exploring the potential of bacterial-derived EVs for targeted enzyme replacement therapy: mechanisms, applications, and future directions. Arch Microbiol. 2025;207:118.
49. Molina-Tijeras JA, Gálvez J, Rodríguez-Cabezas ME. The immunomodulatory properties of extracellular vesicles derived from probiotics: a novel approach for the management of gastrointestinal diseases. Nutrients. 2019;11:1038.
50. Domínguez Rubio AP, D’Antoni CL, Piuri M, Pérez OE. Probiotics, their extracellular vesicles and infectious diseases. Front Microbiol. 2022;13:864720.
51. Piqué N, Berlanga M, Miñana-Galbis D. Health benefits of heat-killed (tyndallized) probiotics: an overview. Int J Mol Sci. 2019;20:2534.
52. Durack J, Lynch SV. Promotion of epithelial barrier integrity via probiotic-derived products. J Pediatr Gastroenterol Nutr. 2017;64:335-6.
53. Liu L, Zheng C, Xu Z, et al. Intranasal administration of Clostridium butyricum and its derived extracellular vesicles alleviate LPS-induced acute lung injury. Microbiol Spectr. 2024;12:e0210824.
54. Zhao Q, Lai J, Jiang Y, et al. Lactiplantibacillus plantarum -derived extracellular vesicles alleviate acute lung injury by inhibiting ferroptosis of macrophages. J Nanobiotechnol. 2025;23:307.
56. Sim S, Lee DH, Kim KS, et al. Micrococcus luteus-derived extracellular vesicles attenuate neutrophilic asthma by regulating miRNAs in airway epithelial cells. Exp Mol Med. 2023;55:196-204.
57. Lee DH, Park HK, Lee HR, et al. Immunoregulatory effects of Lactococcus lactis-derived extracellular vesicles in allergic asthma. Clin Transl Allergy. 2022;12:e12138.
58. Ciprandi G, Schiavetti I, Cioffi L, Pane M, Drago L. The probiotics in pediatric asthma management (PROPAM) study: a post hoc analysis in allergic children. Ann Allergy Asthma Immunol. 2022;129:111-3.
59. La Mantia I, Gelardi M, Drago L, et al. Probiotics in the add-on treatment of rhinosinusitis: a clinical experience. J Biol Regul Homeost Agents. 2020;3:27-34.
60. Drago L, Cioffi L, Giuliano M, et al. The probiotics in pediatric asthma management (PROPAM) study in the primary care setting: a randomized, controlled, double-blind trial with Ligilactobacillus salivarius LS01 (DSM 22775) and Bifidobacterium breve B632 (DSM 24706). J Immunol Res. 2022;2022:3837418.
61. Schmid AM, Razim A, Wysmołek M, et al. Extracellular vesicles of the probiotic bacteria E. coli O83 activate innate immunity and prevent allergy in mice. Cell Commun Signal. 2023;21:297.
62. Preet R, Islam MA, Shim J, et al. Gut commensal Bifidobacterium-derived extracellular vesicles modulate the therapeutic effects of anti-PD-1 in lung cancer. Nat Commun. 2025;16:3500.
63. Park KS, Lässer C, Lötvall J. Extracellular vesicles and the lung: from disease pathogenesis to biomarkers and treatments. Physiol Rev. 2025;105:1733-821.
64. Yang J, Kim EK, Park HJ, McDowell A, Kim YK. The impact of bacteria-derived ultrafine dust particles on pulmonary diseases. Exp Mol Med. 2020;52:338-47.
65. Kim YY, Joh JS, Lee JY. Importance of microbial extracellular vesicle in the pathogenesis of asthma and chronic obstructive pulmonary disease and its diagnostic potential. Asia Pac Allergy. 2020;10:e25.
66. Yang J, Hong G, Kim YS, et al. Lung disease diagnostic model through IgG sensitization to microbial extracellular vesicles. Allergy Asthma Immunol Res. 2020;12:669-83.
67. Kim YS, Choi JP, Kim MH, et al. IgG sensitization to extracellular vesicles in indoor dust is closely associated with the prevalence of non-eosinophilic asthma, COPD, and lung cancer. Allergy Asthma Immunol Res. 2016;8:198-205.
68. Yun H, Seo JH, Kim YK, Yang J. Examining the bacterial diversity including extracellular vesicles in air and soil: implications for human health. PLoS ONE. 2025;20:e0320916.
69. Jang JY, Seo JH, Choi JJ, et al. Insight into microbial extracellular vesicles as key communication materials and their clinical implications for lung cancer (Review). Int J Mol Med. 2025;56:119.
70. Park KS, Lee J, Jang SC, et al. Pulmonary inflammation induced by bacteria-free outer membrane vesicles from Pseudomonas aeruginosa. Am J Respir Cell Mol Biol. 2013;49:637-45.
71. Kim YS, Lee WH, Choi EJ, et al. Extracellular vesicles derived from Gram-negative bacteria, such as Escherichia coli, induce emphysema mainly via IL-17A-mediated neutrophilic inflammation. J Immunol. 2015;194:3361-8.
72. Kim YS, Choi EJ, Lee WH, et al. Extracellular vesicles, especially derived from Gram-negative bacteria, in indoor dust induce neutrophilic pulmonary inflammation associated with both Th1 and Th17 cell responses. Clin Exp Allergy. 2013;43:443-54.
73. Qin S, Xiao W, Zhou C, et al. Pseudomonas aeruginosa: pathogenesis, virulence factors, antibiotic resistance, interaction with host, technology advances and emerging therapeutics. Signal Transduct Target Ther. 2022;7:199.
74. Xie Y, Shi YH, Wang LL, Li CW, Wu M, Xu JF. Outer membrane vesicle contributes to the Pseudomonas aeruginosa resistance to antimicrobial peptides in the acidic airway of bronchiectasis patients. MedComm. 2025;6:e70084.
75. Yang D, Chen X, Wang J, et al. Dysregulated lung commensal bacteria drive interleukin-17B production to promote pulmonary fibrosis through their outer membrane vesicles. Immunity. 2019;50:692-706.e7.
76. Moghaddam ZS, Dehghan A, Halimi S, et al. Bacterial extracellular vesicles: bridging pathogen biology and therapeutic innovation. Acta Biomater. 2025;200:1-20.
77. Hong SW, Kim MR, Lee EY, et al. Extracellular vesicles derived from Staphylococcus aureus induce atopic dermatitis-like skin inflammation. Allergy. 2011;66:351-9.
78. Hong SW, Choi EB, Min TK, et al. An important role of α-hemolysin in extracellular vesicles on the development of atopic dermatitis induced by Staphylococcus aureus. PLoS ONE. 2014;9:e100499.
79. Verta R, Grange C, Skovronova R, et al. Generation of spike-extracellular vesicles (S-EVs) as a tool to mimic SARS-CoV-2 interaction with host cells. Cells. 2022;11:146.
80. Fu Y, Xiong S. Tagged extracellular vesicles with the RBD of the viral spike protein for delivery of antiviral agents against SARS-COV-2 infection. J Control Release. 2021;335:584-95.
81. Giordano NP, Cian MB, Dalebroux ZD. Outer membrane lipid secretion and the innate immune response to gram-negative bacteria. Infect Immun. 2020;88:e00920-19.
82. Chen MY, Cheng TW, Pan YC, et al. Endotoxin-free outer membrane vesicles for safe and modular anticancer immunotherapy. ACS Synth Biol. 2025;14:148-60.
83. Rossi O, Pesce I, Giannelli C, et al. Modulation of endotoxicity of Shigella generalized modules for membrane antigens (GMMA) by genetic lipid A modifications: relative activation of TLR4 and TLR2 pathways in different mutants. J Biol Chem. 2014;289:24922-35.
84. Sartorio MG, Pardue EJ, Feldman MF, Haurat MF. Bacterial outer membrane vesicles: from discovery to applications. Annu Rev Microbiol. 2021;75:609-30.
85. Kawasaki T, Takeda Y, Kumanogoh A. Proteomics of blood extracellular vesicles in inflammatory respiratory diseases for biomarker discovery and new insights into pathophysiology. Inflamm Regen. 2024;44:38.
86. An J, McDowell A, Kim YK, Kim TB. Extracellular vesicle-derived microbiome obtained from exhaled breath condensate in patients with asthma. Ann Allergy Asthma Immunol. 2021;126:729-31.
87. McDowell A, Kang J, Yang J, et al. Machine-learning algorithms for asthma, COPD, and lung cancer risk assessment using circulating microbial extracellular vesicle data and their application to assess dietary effects. Exp Mol Med. 2022;54:1586-95.
88. Park J, Lee JJ, Hong Y, Seo H, Shin TS, Hong JY. Metagenomic analysis of plasma microbial extracellular vesicles in patients receiving mechanical ventilation: a pilot study. J Pers Med. 2022;12:564.
