REFERENCES
2. Cryan JF, O’Riordan KJ, Cowan CSM, et al. The microbiota-gut-brain axis. Physiol Rev. 2019;99:1877-2013.
3. Song C, Chai Z, Chen S, Zhang H, Zhang X, Zhou Y. Intestinal mucus components and secretion mechanisms: what we do and do not know. Exp Mol Med. 2023;55:681-91.
4. Ghosh S, Whitley CS, Haribabu B, Jala VR. Regulation of intestinal barrier function by microbial metabolites. Cell Mol Gastroenterol Hepatol. 2021;11:1463-82.
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. Melo-Marques I, Cardoso SM, Empadinhas N. Bacterial extracellular vesicles at the interface of gut microbiota and immunity. Gut Microbes. 2024;16:2396494.
7. Zou C, Zhang Y, Liu H, Wu Y, Zhou X. Extracellular vesicles: recent insights into the interaction between host and pathogenic bacteria. Front Immunol. 2022;13:840550.
8. Schaack B, Hindré T, Quansah N, Hannani D, Mercier C, Laurin D. Microbiota-derived extracellular vesicles detected in human blood from healthy donors. Int J Mol Sci. 2022;23:13787.
9. Jones EJ, Booth C, Fonseca S, et al. The uptake, trafficking, and biodistribution of Bacteroides thetaiotaomicron generated outer membrane vesicles. Front Microbiol. 2020;11:57.
10. Carvalho AL, Fonseca S, Miquel-Clopés A, et al. Bioengineering commensal bacteria-derived outer membrane vesicles for delivery of biologics to the gastrointestinal and respiratory tract. J Extracell Vesicles. 2019;8:1632100.
11. Dehghani M, Gulvin SM, Flax J, Gaborski TR. Systematic Evaluation of PKH labelling on extracellular vesicle size by nanoparticle tracking analysis. Sci Rep. 2020;10:9533.
12. Yi YW, Lee JH, Kim SY, et al. Advances in analysis of biodistribution of exosomes by molecular imaging. Int J Mol Sci. 2020;21:665.
13. Takov K, Yellon DM, Davidson SM. Confounding factors in vesicle uptake studies using fluorescent lipophilic membrane dyes. J Extracell Vesicles. 2017;6:1388731.
14. Simonsen JB. Pitfalls associated with lipophilic fluorophore staining of extracellular vesicles for uptake studies. J Extracell Vesicles. 2019;8:1582237.
15. Fonseca S, Carvalho AL, Miquel-Clopés A, et al. Extracellular vesicles produced by the human gut commensal bacterium Bacteroides thetaiotaomicron elicit anti-inflammatory responses from innate immune cells. Front Microbiol. 2022;13:1050271.
16. Whitaker WR, Shepherd ES, Sonnenburg JL. Tunable expression tools enable single-cell strain distinction in the gut microbiome. Cell. 2017;169:538-46.e12.
17. Hall MP, Unch J, Binkowski BF, et al. Engineered luciferase reporter from a deep sea shrimp utilizing a novel imidazopyrazinone substrate. ACS Chem Biol. 2012;7:1848-57.
18. England CG, Ehlerding EB, Cai W. NanoLuc: a small luciferase is brightening up the field of bioluminescence. Bioconjug Chem. 2016;27:1175-87.
19. Gupta D, Liang X, Pavlova S, et al. Quantification of extracellular vesicles in vitro and in vivo using sensitive bioluminescence imaging. J Extracell Vesicles. 2020;9:1800222.
20. Troy T, Jekic-McMullen D, Sambucetti L, Rice B. Quantitative comparison of the sensitivity of detection of fluorescent and bioluminescent reporters in animal models. Mol Imaging. 2004;3:9-23.
21. Schaub FX, Reza MS, Flaveny CA, et al. Fluorophore-NanoLuc BRET reporters enable sensitive in vivo optical imaging and flow cytometry for monitoring tumorigenesis. Cancer Res. 2015;75:5023-33.
22. Lázaro-Ibáñez E, Faruqu FN, Saleh AF, et al. Selection of fluorescent, bioluminescent, and radioactive tracers to accurately reflect extracellular vesicle biodistribution in vivo. ACS Nano. 2021;15:3212-27.
23. Valguarnera E, Scott NE, Azimzadeh P, Feldman MF. Surface exposure and packing of lipoproteins into outer membrane vesicles are coupled processes in Bacteroides. mSphere. 2018;3:e00559-18.
24. Juodeikis R, Martins C, Saalbach G, et al. Differential temporal release and lipoprotein loading in B. thetaiotaomicron bacterial extracellular vesicles. J Extracell Vesicles. 2024;13:e12406.
25. Modasia AA, Jones EJ, Martel LM, et al. The use of a multicellular in vitro model to investigate uptake and migration of bacterial extracellular vesicles derived from the human gut commensal Bacteroides thetaiotaomicron. J Extracell Biol. 2023;2:e93.
26. González-González M, Díaz-Zepeda C, Eyzaguirre-Velásquez J, González-Arancibia C, Bravo JA, Julio-Pieper M. Investigating gut permeability in animal models of disease. Front Physiol. 2018;9:1962.
27. Braniste V, Al-Asmakh M, Kowal C, et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med. 2014;6:263ra158.
28. Ji N, Wang F, Wang M, Zhang W, Liu H, Su J. Engineered bacterial extracellular vesicles for central nervous system diseases. J Control Release. 2023;364:46-60.
29. Shi Y, Wang X, Zhang S, et al. Research progress in in vivo tracing technology for extracellular vesicles. Extracell Vesicles Circ Nucl Acids. 2023;4:684-97.
30. Álamo P, Pallarès V, Céspedes MV, et al. Fluorescent dye labeling changes the biodistribution of tumor-targeted nanoparticles. Pharmaceutics. 2020;12:1004.
31. Zhang YN, Poon W, Tavares AJ, McGilvray ID, Chan WCW. Nanoparticle-liver interactions: cellular uptake and hepatobiliary elimination. J Control Release. 2016;240:332-48.
32. Hosseini-Kharat M, Bremmell KE, Prestidge CA. Why do lipid nanoparticles target the liver? Understanding of biodistribution and liver-specific tropism. Mol Ther Methods Clin Dev. 2025;33:101436.
33. He Y, Wang Y, Wang L, Jiang W, Wilhelm S. Understanding nanoparticle-liver interactions in nanomedicine. Expert Opin Drug Deliv. 2024;21:829-43.
34. Parthasarathy G, Hirsova P, Kostallari E, Sidhu GS, Ibrahim SH, Malhi H. Extracellular vesicles in hepatobiliary health and disease. Compr Physiol. 2023;13:4631-58.
35. Gandek TB, van der Koog L, Nagelkerke A. A comparison of cellular uptake mechanisms, delivery efficacy, and intracellular fate between liposomes and extracellular vesicles. Adv Healthc Mater. 2023;12:e2300319.
36. Boudna M, Campos AD, Vychytilova-Faltejskova P, Machackova T, Slaby O, Souckova K. Strategies for labelling of exogenous and endogenous extracellular vesicles and their application for in vitro and in vivo functional studies. Cell Commun Signal. 2024;22:171.
37. Lee KE, Kim JK, Han SK, et al. The extracellular vesicle of gut microbial Paenalcaligenes hominis is a risk factor for vagus nerve-mediated cognitive impairment. Microbiome. 2020;8:107.
38. Ma X, Shin YJ, Yoo JW, Park HS, Kim DH. Extracellular vesicles derived from Porphyromonas gingivalis induce trigeminal nerve-mediated cognitive impairment. J Adv Res. 2023;54:293-303.
39. Palacios E, Lobos-González L, Guerrero S, et al.
40. Park AM, Tsunoda I.
41. Xie J, Cools L, Van Imschoot G, et al.
42. Bittel M, Reichert P, Sarfati I, et al. Visualizing transfer of microbial biomolecules by outer membrane vesicles in microbe-host-communication in vivo. J Extracell Vesicles. 2021;10:e12159.
43. Ha JY, Choi SY, Lee JH, Hong SH, Lee HJ. Delivery of periodontopathogenic extracellular vesicles to brain monocytes and microglial IL-6 promotion by RNA cargo. Front Mol Biosci. 2020;7:596366.
44. Huang Y, Beringhs AO, Chen Q, et al. Genetically engineered bacterial outer membrane vesicles with expressed nanoluciferase reporter for in vivo bioluminescence kinetic modeling through noninvasive imaging. ACS Appl Bio Mater. 2019;2:5608-15.
45. Wei S, Peng W, Mai Y, et al. Outer membrane vesicles enhance tau phosphorylation and contribute to cognitive impairment. J Cell Physiol. 2020;235:4843-55.
46. Meng D, Lai Y, Zhang L, et al. Helicobacter pylori outer membrane vesicles directly promote Aβ aggregation and enhance Aβ toxicity in APP/PS1 mice. Commun Biol. 2024;7:1474.
47. Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009;9:313-23.
48. Durant L, Stentz R, Noble A, et al.
49. Weinberger V, Darnhofer B, Thapa HB, et al. Proteomic and metabolomic profiling of extracellular vesicles produced by human gut archaea. Nat Commun. 2025;16:5094.







