Microbiota-Derived Extracellular Vesicles Detected in Human Blood from Healthy Donors

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Nov 26

PMID 36430266

Authors

Beatrice Schaack

Thomas Hindre

Nyamekye Quansah

Dalil Hannani

Corinne Mercier

David Laurin

Affiliations

Soon will be listed here.

Abstract

The microbiota constitutes an important part of the holobiont in which extracellular vesicles (EVs) are key players in health, especially regarding inter- and intra-kingdom communications. Analysis of EVs from the red blood cell concentrates of healthy donors revealed variable amounts of OmpA and LPS in 12 of the 14 analyzed samples, providing indirect experimental evidence of the presence of microbiota EVs in human circulating blood in the absence of barrier disruption. To investigate the role of these microbiota EVs, we tracked the fusion of fluorescent EVs with blood mononuclear cells and showed that, in the circulating blood, these EVs interacted almost exclusively with monocytes. This study demonstrates that bacterial EVs constitute critical elements of the host-microbiota cellular communication. The analysis of bacterial EVs should thus be systematically included in any characterization of human EVs.

Citing Articles

Oral delivery of therapeutic proteins by engineered bacterial type zero secretion system.

Gong X, Liu S, Xia B, Wan Y, Zhang S, Zhang B Nat Commun. 2025; 16(1):1862.

PMID: 39984501 PMC: 11845744. DOI: 10.1038/s41467-025-57153-6.

Stoichiometric constraints for detection of EV-borne biomarkers in blood.

Zarovni N, Mladenovic D, Brambilla D, Panico F, Chiari M J Extracell Vesicles. 2025; 14(2):e70034.

PMID: 39901737 PMC: 11791308. DOI: 10.1002/jev2.70034.

Regulation of hepatic lipid metabolism by intestine epithelium-derived exosomes.

Feng T, Liang Y, Sun L, Feng L, Min J, Mulholland M Life Metab. 2025; 2(6):load044.

PMID: 39872853 PMC: 11749469. DOI: 10.1093/lifemeta/load044.

Staphylococcus aureus vesicles impair cutaneous wound healing through p38 MAPK-MerTK cleavage-mediated inhibition of macrophage efferocytosis.

Ou J, Li K, Yuan H, Du S, Wang T, Deng Q Cell Commun Signal. 2025; 23(1):14.

PMID: 39780180 PMC: 11708000. DOI: 10.1186/s12964-024-01994-z.

The emerging role of bacterial extracellular vesicles in human cancers.

Liang A, Korani L, Yeung C, Tey S, Yam J J Extracell Vesicles. 2024; 13(10):e12521.

PMID: 39377479 PMC: 11460218. DOI: 10.1002/jev2.12521.

References

Aurell C, Wistrom A . Critical aggregation concentrations of gram-negative bacterial lipopolysaccharides (LPS). Biochem Biophys Res Commun. 1999; 253(1):119-23. DOI: 10.1006/bbrc.1998.9773. View

Yang Z, Liu X, Wu Y, Peng J, Wei H . Effect of the Microbiome on Intestinal Innate Immune Development in Early Life and the Potential Strategy of Early Intervention. Front Immunol. 2022; 13:936300. PMC: 9344006. DOI: 10.3389/fimmu.2022.936300. View

Chronopoulos A, Kalluri R . Emerging role of bacterial extracellular vesicles in cancer. Oncogene. 2020; 39(46):6951-6960. PMC: 7557313. DOI: 10.1038/s41388-020-01509-3. View

Laulagnier K, Javalet C, Hemming F, Chivet M, Lachenal G, Blot B . Amyloid precursor protein products concentrate in a subset of exosomes specifically endocytosed by neurons. Cell Mol Life Sci. 2017; 75(4):757-773. PMC: 11105273. DOI: 10.1007/s00018-017-2664-0. View

Schwechheimer C, Kuehn M . Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions. Nat Rev Microbiol. 2015; 13(10):605-19. PMC: 5308417. DOI: 10.1038/nrmicro3525. View

Ellis T, Leiman S, Kuehn M . Naturally produced outer membrane vesicles from Pseudomonas aeruginosa elicit a potent innate immune response via combined sensing of both lipopolysaccharide and protein components. Infect Immun. 2010; 78(9):3822-31. PMC: 2937433. DOI: 10.1128/IAI.00433-10. View

Jones E, Booth C, Fonseca S, Parker A, Cross K, Miquel-Clopes A . The Uptake, Trafficking, and Biodistribution of Generated Outer Membrane Vesicles. Front Microbiol. 2020; 11:57. PMC: 7015872. DOI: 10.3389/fmicb.2020.00057. View

Alvarez C, Badia J, Bosch M, Gimenez R, Baldoma L . Outer Membrane Vesicles and Soluble Factors Released by Probiotic Nissle 1917 and Commensal ECOR63 Enhance Barrier Function by Regulating Expression of Tight Junction Proteins in Intestinal Epithelial Cells. Front Microbiol. 2016; 7:1981. PMC: 5156689. DOI: 10.3389/fmicb.2016.01981. View

Tulkens J, Vergauwen G, Van Deun J, Geeurickx E, Dhondt B, Lippens L . Increased levels of systemic LPS-positive bacterial extracellular vesicles in patients with intestinal barrier dysfunction. Gut. 2018; 69(1):191-193. PMC: 6943244. DOI: 10.1136/gutjnl-2018-317726. View

10.

Zegarra-Ruiz D, Kim D, Norwood K, Kim M, Wu W, Saldana-Morales F . Thymic development of gut-microbiota-specific T cells. Nature. 2021; 594(7863):413-417. PMC: 8323488. DOI: 10.1038/s41586-021-03531-1. View

11.

Santos N, Silva A, Castanho M, Martins-Silva J, Saldanha C . Evaluation of lipopolysaccharide aggregation by light scattering spectroscopy. Chembiochem. 2003; 4(1):96-100. DOI: 10.1002/cbic.200390020. View

12.

Avila-Calderon E, Ruiz-Palma M, Aguilera-Arreola M, Velazquez-Guadarrama N, Ruiz E, Gomez-Lunar Z . Outer Membrane Vesicles of Gram-Negative Bacteria: An Outlook on Biogenesis. Front Microbiol. 2021; 12:557902. PMC: 7969528. DOI: 10.3389/fmicb.2021.557902. View

13.

Stentz R, Carvalho A, Jones E, Carding S . Fantastic voyage: the journey of intestinal microbiota-derived microvesicles through the body. Biochem Soc Trans. 2018; 46(5):1021-1027. PMC: 6195637. DOI: 10.1042/BST20180114. View

14.

Lee K, Kim J, Han S, Lee D, Lee H, Yim S . The extracellular vesicle of gut microbial Paenalcaligenes hominis is a risk factor for vagus nerve-mediated cognitive impairment. Microbiome. 2020; 8(1):107. PMC: 7364628. DOI: 10.1186/s40168-020-00881-2. View

15.

Paisse S, Valle C, Servant F, Courtney M, Burcelin R, Amar J . Comprehensive description of blood microbiome from healthy donors assessed by 16S targeted metagenomic sequencing. Transfusion. 2016; 56(5):1138-47. DOI: 10.1111/trf.13477. View

16.

Park J, Choi J, Lee Y, Lee J, Lee E, Kwon H . Metagenome Analysis of Bodily Microbiota in a Mouse Model of Alzheimer Disease Using Bacteria-derived Membrane Vesicles in Blood. Exp Neurobiol. 2018; 26(6):369-379. PMC: 5746502. DOI: 10.5607/en.2017.26.6.369. View

17.

Lee Y, Park J, Lee E, Yang J, Jeong B, Kim Y . Rapid Assessment of Microbiota Changes in Individuals with Autism Spectrum Disorder Using Bacteria-derived Membrane Vesicles in Urine. Exp Neurobiol. 2017; 26(5):307-317. PMC: 5661063. DOI: 10.5607/en.2017.26.5.307. View

18.

Bonnington K, Kuehn M . Protein selection and export via outer membrane vesicles. Biochim Biophys Acta. 2013; 1843(8):1612-9. PMC: 4317292. DOI: 10.1016/j.bbamcr.2013.12.011. View

19.

Thevaranjan N, Puchta A, Schulz C, Naidoo A, Szamosi J, Verschoor C . Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction. Cell Host Microbe. 2017; 21(4):455-466.e4. PMC: 5392495. DOI: 10.1016/j.chom.2017.03.002. View

20.

An J, Kim S, Hwang D, Lee K, Kim M, Yang E . Caspase-4 disaggregates lipopolysaccharide micelles via LPS-CARD interaction. Sci Rep. 2019; 9(1):826. PMC: 6351570. DOI: 10.1038/s41598-018-36811-4. View