Outer Membrane Vesicles of a Human Commensal Mediate Immune Regulation and Disease Protection
Open accessAbstract
Commensal bacteria impact host health and immunity through various mechanisms, including the production of immunomodulatory molecules. Bacteroides fragilis produces a capsular polysaccharide (PSA), which induces regulatory T cells and mucosal tolerance. However, unlike pathogens, which employ secretion systems, the mechanisms by which commensal bacteria deliver molecules to the host remain unknown. We reveal that Bacteroides fragilis releases PSA in outer membrane vesicles (OMVs) that induce immunomodulatory effects and prevent experimental colitis. Dendritic cells (DCs) sense OMV-associated PSA through TLR2, resulting in enhanced regulatory T cells and anti-inflammatory cytokine production. OMV-induced signaling in DCs requires growth arrest and DNA-damage-inducible protein (Gadd45α). DCs treated with PSA-containing OMVs prevent experimental colitis, whereas Gadd45α(-/-) DCs are unable to promote regulatory T cell responses or suppress proinflammatory cytokine production and host pathology. These findings demonstrate that OMV-mediated delivery of a commensal molecule prevents disease, uncovering a mechanism of interkingdom communication between the microbiota and mammals.
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PSA produced by Leuconostoc mesenteroides strain NTM048 or Bacteroides fragilis acts as an immunostimulant to enhance the mucosal barrier and influence systemic immune responses.
“Furthermore, PSA produced by Leuconostoc mesenteroides strain NTM048 or Bacteroides fragilis acts as an immunostimulant to enhance the mucosal barrier and influence systemic immune responses [111, 112] (Fig. 5G).”
From Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies (2022) · cites this paper as [112]
Some bacterial species promote Treg development through polysaccharide A and TLR signaling to dendritic cells.
“some bacterial species have been shown to drive Treg development via alternative pathways dependent on polysaccharide A and TLR signaling to dendritic cells”
From The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy (2018) · cites this paper as Shen et al., 2012
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Cites
The gut microbiota shapes intestinal immune responses during health and disease
Round, J. L., & Mazmanian, S. K. (2009) · Nature Reviews Immunology · doi:10.1038/nri2515 · Cited by 5,029 · see citing works
Self-citationUnravelling the pathogenesis of inflammatory bowel disease
Xavier, R. J., & Podolsky, D. K. (2007) · Nature · doi:10.1038/nature06005 · Cited by 4,364 · see citing works
Evolution of mammals and their gut microbes
Ley, R. E., Hamady, M., Lozupone, C., Turnbaugh, P. J., Ramey, R. R., Bircher, J. S., Schlegel, M. L., Tucker, T. A., Schrenzel, M. D., Knight, R., et al. (2008) · Science · doi:10.1126/science.1155725 · Cited by 3,747 · see citing works
An Immunomodulatory Molecule of Symbiotic Bacteria Directs Maturation of the Host Immune System
Mazmanian, S. K., Liu, C. H., Tzianabos, A. O., & Kasper, D. L. (2005) · Cell · doi:10.1016/j.cell.2005.05.007 · Cited by 2,910 · see citing works
Self-citationRecognition of microorganisms and activation of the immune response
Medzhitov, R. (2007) · Nature · doi:10.1038/nature06246 · Cited by 2,862 · see citing works
Rescigno, M., Urbano, M., Valzasina, B., Francolini, M., Rotta, G., Bonasio, R., Granucci, F., Kraehenbuhl, J.-P., & Ricciardi‐Castagnoli, P. (2001) · Nature Immunology · doi:10.1038/86373 · Cited by 2,554 · see citing works
A microbial symbiosis factor prevents intestinal inflammatory disease
Mazmanian, S. K., Round, J. L., & Kasper, D. L. (2008) · Nature · doi:10.1038/nature07008 · Cited by 2,340 · see citing works
Self-citationRound, J. L., & Mazmanian, S. K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909122107 · Cited by 2,233 · see citing works
Self-citationThe Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota
Round, J. L., Lee, S. M., Li, J., Tran, G., Jabri, B., Chatila, T. A., & Mazmanian, S. K. (2011) · Science · doi:10.1126/science.1206095 · Cited by 1,604 · see citing works
Self-citationRegulatory T Cell-Derived Interleukin-10 Limits Inflammation at Environmental Interfaces
Rubtsov, Y. P., Rasmussen, J. P., Chi, E. Y., Fontenot, J., Castelli, L., Ye, X., Treuting, P., Siewe, L., Roers, A., Henderson, W. R., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.02.017 · Cited by 1,586 · see citing works
Chemically induced mouse models of intestinal inflammation
Wirtz, S., Neufert, C., Weigmann, B., & Neurath, M. F. (2007) · Nature Protocols · doi:10.1038/nprot.2007.41 · Cited by 1,567 · see citing works
Structures of Gram-Negative Cell Walls and Their Derived Membrane Vesicles
Beveridge, T. J. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.16.4725-4733.1999 · Cited by 1,533 · see citing works
Gut immune maturation depends on colonization with a host-specific microbiota
Chung, H., Pamp, S. J., Hill, J. A., Surana, N. K., Edelman, S. M., Troy, E. B., Reading, N. C., Villablanca, E. J., Wang, S., Mora, J. R., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.037 · Cited by 1,241 · see citing works
Has the Microbiota Played a Critical Role in the Evolution of the Adaptive Immune System?
Lee, Y. K., & Mazmanian, S. K. (2010) · Science · doi:10.1126/science.1195568 · Cited by 1,115 · see citing works
Self-citationMechanisms of impaired regulation by CD4+CD25+FOXP3+ regulatory T cells in human autoimmune diseases
Buckner, J. H. (2010) · Nature reviews. Immunology · doi:10.1038/nri2889 · Cited by 790 · see citing works
Release of outer membrane vesicles by Gram‐negative bacteria is a novel envelope stress response
McBroom, A. J., & Kuehn, M. J. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05522.x · Cited by 734 · see citing works
Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10
Sun, J., Madan, R., Karp, C. L., & Braciale, T. J. (2009) · Nature Medicine · doi:10.1038/nm.1929 · Cited by 616 · see citing works
Self-citationIL-10–producing and naturally occurring CD4+ Tregs: limiting collateral damage
O’Garra, A., Vieira, P. L., Vieira, P., & Goldfeld, A. E. (2004) · Journal of Clinical Investigation · doi:10.1172/jci23215 · Cited by 530 · see citing works
Ochoa-Repáraz, J., Mielcarz, D. W., Wang, Y., Begum-Haque, S., Dasgupta, S., Kasper, D. L., & Kasper, L. H. (2010) · Mucosal Immunology · doi:10.1038/mi.2010.29 · Cited by 507 · see citing works
Regulatory Lymphocytes and Intestinal Inflammation
Ízcue, A., Coombes, J. L., & Powrie, F. M. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132657 · Cited by 505 · see citing works
Regulatory T cell development in the absence of functional Foxp3
Lin, W. X., Haribhai, D., Relland, L. M., Truong, N., Carlson, M. R. J., Williams, C. B., & Chatila, T. A. (2007) · Nature Immunology · doi:10.1038/ni1445 · Cited by 485 · see citing works
Diversity in the contribution of interleukin‐10 to T‐cell‐mediated immune regulation
Maynard, C. L., & Weaver, C. T. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00711.x · Cited by 404 · see citing works
Special delivery: vesicle trafficking in prokaryotes
Mashburn‐Warren, L., & Whiteley, M. (2006) · Molecular Microbiology · doi:10.1111/j.1365-2958.2006.05272.x · Cited by 392 · see citing works
Ochoa-Repáraz, J., Mielcarz, D. W., Ditrio, L. E., Burroughs, A. R., Begum-Haque, S., Dasgupta, S., Kasper, D. L., & Kasper, L. H. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1001443 · Cited by 367 · see citing works
Extensive surface diversity of a commensal microorganism by multiple DNA inversions
Krinos, C. M., Coyne, M. J., Weinacht, K. G., Tzianabos, A. O., Kasper, D. L., & Comstock, L. E. (2001) · Nature · doi:10.1038/35107092 · Cited by 359 · see citing works
Common Themes in the Design and Function of Bacterial Effectors
Galán, J. E. (2009) · Cell Host & Microbe · doi:10.1016/j.chom.2009.04.008 · Cited by 319 · see citing works
Biogenesis of bacterial membrane vesicles
Deatherage, B. L., Lara, J. C., Bergsbaken, T., Barrett, S. L. R., Lara, S. L., & Cookson, B. T. (2009) · Molecular Microbiology · doi:10.1111/j.1365-2958.2009.06731.x · Cited by 303 · see citing works
Extensive DNA Inversions in the B. fragilis Genome Control Variable Gene Expression
Cerdeño-Tárraga, A. M., Patrick, S., Crossman, L. C., Blakely, G., Abratt, V. R., Lennard, N. J., Poxton, I. R., Duerden, B. I., Harris, B. R., Quail, M. A., et al. (2005) · Science · doi:10.1126/science.1107008 · Cited by 298 · see citing works
A bacterial carbohydrate links innate and adaptive responses through Toll-like receptor 2
Wang, Q., McLoughlin, R. M., Cobb, B. A., Charrel-Dennis, M., Zaleski, K. J., Golenbock, D. T., Tzianabos, A. O., & Kasper, D. L. (2006) · The Journal of Experimental Medicine · doi:10.1084/jem.20062008 · Cited by 277 · see citing works
Kesty, N. C., & Kuehn, M. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307628200 · Cited by 230 · see citing works
The hologenome theory of evolution contains Lamarckian aspects within a Darwinian framework
Rosenberg, E., Sharon, G., & Zilber‐Rosenberg, I. (2009) · Environmental Microbiology · doi:10.1111/j.1462-2920.2009.01995.x · Cited by 189 · see citing works
Mice Lacking the p53-Effector Gene Gadd45a Develop a Lupus-Like Syndrome
Salvador, J. M., Hollander, M. C., Nguyen, A. T., Kopp, J. B., Barisoni, L. M. C., Moore, J. K., Ashwell, J. D., & Fornace, A. J. (2002) · Immunity · doi:10.1016/s1074-7613(02)00302-3 · Cited by 188 · see citing works
Self-citationHorstman, A. L., & Kuehn, M. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203740200 · Cited by 165 · see citing works
Regulation of surface architecture by symbiotic bacteria mediates host colonization
Liu, C., Lee, S. M., Vanlare, J. M., Kasper, D. L., & Mazmanian, S. (2008) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0709266105 · Cited by 126 · see citing works
Self-citationPolysaccharide Biosynthesis Locus Required for Virulence ofBacteroides fragilis
Coyne, M. J., Tzianabos, A. O., Mallory, B. C., Carey, V. J., Kasper, D. L., & Comstock, L. E. (2001) · Infection and Immunity · doi:10.1128/iai.69.7.4342-4350.2001 · Cited by 100 · see citing works
The autoimmune suppressor Gadd45α inhibits the T cell alternative p38 activation pathway
Salvador, J. M., Mittelstadt, P. R., Belova, G. I., Fornace, A. J., & Ashwell, J. D. (2005) · Nature Immunology · doi:10.1038/ni1176 · Cited by 100 · see citing works
Self-citationIL-10 gene therapy prevents TNBS-induced colitis
Lindsay, J. O., van Montfrans, C., Brennan, F. M., van Deventer, S. J. H., Drillenburg, P., Hodgson, H. J. F., Velde, A. A. T., & Rodríguez-Peña, M. S. (2002) · Gene Therapy · doi:10.1038/sj.gt.3301841 · Cited by 80 · see citing works
Patrick, S., McKenna, J. P., Seamus, O., & DERMOTT, E. (1996) · Microbial Pathogenesis · doi:10.1006/mpat.1996.0018 · Cited by 79 · see citing works
Paeonol attenuates TNBS-induced colitis by inhibiting NF-kappaB and STAT1 transactivation.
Ishiguro, K., Ando, T., Maeda, O., Hasegawa, M., Kadomatsu, K., Ohmiya, N., Niwa, Y., Xavier, R., & Goto, H. (2006) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2006.07.002 · Cited by 77 · see citing works
Separation of capsulate and non-capsulate Bacteroides fragilis on a discontinuous density gradient
Patrick, S., & REID, J. H. (1983) · Journal of Medical Microbiology · doi:10.1099/00222615-16-2-239 · Cited by 33 · see citing works
Gadd45α Regulates p38-Dependent Dendritic Cell Cytokine Production and Th1 Differentiation
Jirmanova, L., Jankovic, D. L., Fornace, A. J., & Ashwell, J. D. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.7.4153 · Cited by 29 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Role of the gut microbiota in immunity and inflammatory disease
Kamada, N., Seo, S.-U., Chen, G. Y., & Núñez, G. (2013) · Nature reviews. Immunology · doi:10.1038/nri3430 · Cited by 2,256 · see citing works
Outer-membrane vesicles from Gram-negative bacteria: biogenesis and functions
Schwechheimer, C., & Kuehn, M. J. (2015) · Nature Reviews Microbiology · doi:10.1038/nrmicro3525 · Cited by 1,932 · see citing works
The microbiota in adaptive immune homeostasis and disease
Honda, K., & Littman, D. R. (2016) · Nature · doi:10.1038/nature18848 · Cited by 1,846 · see citing works
The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy
Gopalakrishnan, V., Helmink, B. A., Spencer, C. N., Reuben, A., & Wargo, J. A. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.015 · Cited by 1,392 · see citing works
Extracellular vesicles as tools and targets in therapy for diseases
Kumar, M. A., Baba, S. K., Sadida, H. Q., Al-Marzooqi, S. K., Jerobin, J., Altemani, F. H., Algehainy, N. A., Alanazi, M. A., Abou‐Samra, A., Kumar, R., et al. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01735-1 · Cited by 1,447 · see citing works
Homeostatic Immunity and the Microbiota
Belkaid, Y., & Harrison, O. J. (2017) · Immunity · doi:10.1016/j.immuni.2017.04.008 · Cited by 1,261 · see citing works
Gut Bacteroides species in health and disease
Zafar, H., & Saier, M. H. (2021) · Gut Microbes · doi:10.1080/19490976.2020.1848158 · Cited by 1,258 · see citing works
Defining dysbiosis and its influence on host immunity and disease
Petersen, C., & Round, J. L. (2014) · Cellular Microbiology · doi:10.1111/cmi.12308 · Cited by 1,185 · see citing works
Immune modulation by bacterial outer membrane vesicles
Kaparakis‐Liaskos, M., & Ferrero, R. L. (2015) · Nature reviews. Immunology · doi:10.1038/nri3837 · Cited by 1,028 · see citing works
Chelakkot, C., Choi, Y., Kim, D., Park, H. T., Ghim, J., Kwon, Y., Jeon, J., Kim, M.-S., Jee, Y., Gho, Y. S., et al. (2018) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.282 · Cited by 852 · see citing works
New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD
Larabi, A. B., Barnich, N., & Nguyen, H. T. T. (2019) · Autophagy · doi:10.1080/15548627.2019.1635384 · Cited by 840 · see citing works
Sartor, R. B., & Wu, G. D. (2017) · Gastroenterology · doi:10.1053/j.gastro.2016.10.012 · Cited by 808 · see citing works
The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic strategies
Zitvogel, L., Ma, Y., Raoult, D., Kroemer, G., & Gajewski, T. F. (2018) · Science · doi:10.1126/science.aar6918 · Cited by 777 · see citing works
Bacterial Outer Membrane Vesicles Mediate Cytosolic Localization of LPS and Caspase-11 Activation
Vanaja, S. K., Russo, A. J., Behl, B., Banerjee, I., Yankova, M. P., Deshmukh, S. D., & Rathinam, V. A. K. (2016) · Cell · doi:10.1016/j.cell.2016.04.015 · Cited by 728 · see citing works
Emerging role of extracellular vesicles in inflammatory diseases
Buzás, E. I., György, B., Nagy, G., Falus, A., & Gay, S. (2014) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2014.19 · Cited by 673 · see citing works
Innate immune recognition of the microbiota promotes host-microbial symbiosis
Chu, H., & Mazmanian, S. K. (2013) · Nature Immunology · doi:10.1038/ni.2635 · Cited by 630 · see citing works
Self-citationRole of intestinal microbiota and metabolites on gut homeostasis and human diseases
Lin, L., & Zhang, J. (2017) · BMC Immunology · doi:10.1186/s12865-016-0187-3 · Cited by 731 · see citing works
Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease
Chu, H., Khosravi, A., Kusumawardhani, I. P., Kwon, A. H. K., Vasconcelos, A. C., Cunha, L. D., Mayer, A. E., Shen, Y., Wu, W.-L., Kambal, A., et al. (2016) · Science · doi:10.1126/science.aad9948 · Cited by 647 · see citing works
Self-citationAn insider's perspective: Bacteroides as a window into the microbiome
Wexler, A. G., & Goodman, A. L. (2017) · Nature Microbiology · doi:10.1038/nmicrobiol.2017.26 · Cited by 624 · see citing works
Composition and functions of bacterial membrane vesicles
Toyofuku, M., Schild, S., Kaparakis‐Liaskos, M., & Eberl, L. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-023-00875-5 · Cited by 607 · see citing works
Cullin, N., Azevedo Antunes, C., Straussman, R., Stein-Thoeringer, C. K., & Elinav, E. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.08.006 · Cited by 578 · see citing works
The Gastrointestinal Microbiome: A Review
Barko, P. C., McMichael, M. A., Swanson, K. S., & Williams, D. A. (2018) · Journal of Veterinary Internal Medicine · doi:10.1111/jvim.14875 · Cited by 750 · see citing works
Hiippala, K., Jouhten, H., Ronkainen, A., Hartikainen, A., Kainulainen, V., Jalanka, J., & Satokari, R. M. (2018) · Nutrients · doi:10.3390/nu10080988 · Cited by 599 · see citing works
Development and maintenance of intestinal regulatory T cells
Tanoue, T., Atarashi, K., & Honda, K. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.36 · Cited by 553 · see citing works
Kang, C.-S., Ban, M., Choi, E.-J., Moon, H.-G., Jeon, J.-S., Kim, D.-K., Park, S.-K., Jeon, S. G., Roh, T.-Y., Myung, S.-J., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076520 · Cited by 543 · see citing works
Therapeutic Applications of Extracellular Vesicles: Clinical Promise and Open Questions
György, B., Hung, M. E., Breakefield, X. O., & Leonard, J. N. (2014) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010814-124630 · Cited by 512 · see citing works
The role of inflammation and the gut microbiome in depression and anxiety
Peirce, J. M., & Alviña, K. (2019) · Journal of Neuroscience Research · doi:10.1002/jnr.24476 · Cited by 466 · see citing works
Quantitative imaging of gut microbiota spatial organization
Earle, K. A., Billings, G., Sigal, M., Lichtman, J. S., Hansson, G. C., Elias, J. E., Amieva, M. R., Huang, K. C., & Sonnenburg, J. L. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.09.002 · Cited by 433 · see citing works
Microbiota‐derived extracellular vesicles in interkingdom communication in the gut
Díaz‐Garrido, N., Badı́a, J., & Baldomà, L. (2021) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12161 · Cited by 413 · see citing works
Horizontal transfer of antibiotic resistance genes in the human gut microbiome
McInnes, R. S., McCallum, G. E., Lamberte, L. E., & van Schaik, W. (2020) · Current Opinion in Microbiology · doi:10.1016/j.mib.2020.02.002 · Cited by 401 · see citing works
Bacterial Outer Membrane Vesicles: From Discovery to Applications
Sartorio, M. G., Pardue, E. J., Feldman, M. F., & Haurat, M. F. (2021) · Annual Review of Microbiology · doi:10.1146/annurev-micro-052821-031444 · Cited by 398 · see citing works
Mucin-type O-glycans and their roles in intestinal homeostasis
Bergstrom, K. S. B., & Xia, L. (2013) · Glycobiology · doi:10.1093/glycob/cwt045 · Cited by 360 · see citing works
Bacteroides fragilis subverts mucosal biology: from symbiont to colon carcinogenesis
Sears, C. L., Geis, A. L., & Housseau, F. (2014) · Journal of Clinical Investigation · doi:10.1172/jci72334 · Cited by 354 · see citing works
Turroni, F., Ventura, M., Buttó, L. F., Duranti, S., O’Toole, P. W., Motherway, M. O., & van Sinderen, D. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1318-0 · Cited by 336 · see citing works
The microbiome and regulation of mucosal immunity
McDermott, A. J., & Huffnagle, G. B. (2013) · Immunology · doi:10.1111/imm.12231 · Cited by 335 · see citing works
Hayashi, A., Sato, T., Kamada, N., Mikami, Y., Matsuoka, K., Hisamatsu, T., Hibi∥, T., Roers, A., Yagita∥, H., Ohteki, T., et al. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2013.05.013 · Cited by 331 · see citing works
Release of Staphylococcus aureus extracellular vesicles and their application as a vaccine platform
Wang, X., Thompson, C. D., Weidenmaier, C., & Lee, J. C. (2018) · Nature Communications · doi:10.1038/s41467-018-03847-z · Cited by 331 · see citing works
Mining the microbiota for microbial and metabolite-based immunotherapies
Skelly, A. N., Sato, Y., Kearney, S., & Honda, K. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0144-5 · Cited by 306 · see citing works
Modulation of immune development and function by intestinal microbiota
Kabat, A. M., Srinivasan, N., & Maloy, K. J. (2014) · Trends in Immunology · doi:10.1016/j.it.2014.07.010 · Cited by 312 · see citing works
Dasgupta, S., Erturk-Hasdemir, D., Ochoa-Reparaz, J., Reinecker, H.-C., & Kasper, D. L. (2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.03.006 · Cited by 292 · see citing works
Ramakrishna, C., Kujawski, M., Chu, H., Li, L., Mazmanian, S. K., & Cantin, E. M. (2019) · Nature Communications · doi:10.1038/s41467-019-09884-6 · Cited by 284 · see citing works
Self-citationThe impacts of natural polysaccharides on intestinal microbiota and immune responses – a review
Tang, C., Ding, R., Sun, J. G., Liu, J., Kan, J., & Jin, C. (2019) · Food & Function · doi:10.1039/c8fo01946k · Cited by 281 · see citing works
Microbiota–host communications: Bacterial extracellular vesicles as a common language
Palomino, R. A. Ñ., Vanpouille, C., Costantini, P. E., & Margolis, L. B. (2021) · PLoS Pathogens · doi:10.1371/journal.ppat.1009508 · Cited by 278 · see citing works
Drug-microbiota interactions: an emerging priority for precision medicine
Zhao, Q. C., Chen, Y., Huang, W., Zhou, H., & Zhang, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01619-w · Cited by 296 · see citing works
Preferential Packing of Acidic Glycosidases and Proteases into Bacteroides Outer Membrane Vesicles
Elhenawy, W., Debelyy, M. O., & Feldman, M. F. (2014) · mBio · doi:10.1128/mbio.00909-14 · Cited by 274 · see citing works
Yue, Y., Xu, J., Li, Y., Cheng, K., Feng, Q., Ma, X., Ma, N., Zhang, T., Wang, X., Zhao, X., et al. (2022) · Nature Biomedical Engineering · doi:10.1038/s41551-022-00886-2 · Cited by 269 · see citing works
Caruana, J. C., & Walper, S. A. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.00432 · Cited by 264 · see citing works
Ashrafian, F., Shahryari, A., Behrouzi, A., Moradi, H. R., Raftar, S. K. A., Lari, A., Hadifar, S., Yaghoubfar, R., Badi, S. A., Khatami, S., et al. (2019) · Frontiers in Microbiology · doi:10.3389/fmicb.2019.02155 · Cited by 261 · see citing works
Effectiveness of probiotics, prebiotics, and prebiotic‐like components in common functional foods
Peng, M., Tabashsum, Z., Anderson, M., Truong, A., Houser, A., Padilla, J., Akmel, A., Bhatti, J., Rahaman, S. O., & Biswas, D. (2020) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12565 · Cited by 258 · see citing works
Gut microbiome and cancer immunotherapy
Li, W., Deng, Y., Chu, Q., & Zhang, P. (2019) · Cancer Letters · doi:10.1016/j.canlet.2019.01.015 · Cited by 258 · see citing works
Extracellular Vesicles from Child Gut Microbiota Enter into Bone to Preserve Bone Mass and Strength
Liu, J., Chen, C., Liu, Z., Luo, Z., Rao, S., Jin, L., Wan, T., Yue, T., Tan, Y., Yin, H., et al. (2021) · Advanced Science · doi:10.1002/advs.202004831 · Cited by 256 · see citing works
Microbiota-mediated inflammation and antimicrobial defense in the intestine
Caballero, S., & Pamer, E. G. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120238 · Cited by 238 · see citing works
Hickey, C., Kuhn, K. A., Donermeyer, D. L., Porter, N. T., Jin, C., Cameron, E. A., Jung, H., Kaiko, G. E., Wegorzewska, M. M., Malvin, N. P., et al. (2015) · Cell Host & Microbe · doi:10.1016/j.chom.2015.04.002 · Cited by 247 · see citing works
Fábrega, M.-J., Rodríguez-Nogales, A., Garrido-Mesa, J., Algieri, F., Badía, J., Giménez, R., Gálvez, J., & Baldomà, L. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.01274 · Cited by 240 · see citing works
Li, Z., Wang, Y., Liu, J., Rawding, P. A., Bu, J., Hong, S., & Hu, Q. (2021) · Advanced Materials · doi:10.1002/adma.202102580 · Cited by 243 · see citing works
Verma, R., Lee, C., Jeun, E.-J., Yi, J., Kim, K. S., Ghosh, A., Byun, S., Lee, C.-G., Kang, H.-J., Kim, G.-C., et al. (2018) · Science Immunology · doi:10.1126/sciimmunol.aat6975 · Cited by 242 · see citing works
Host- and Microbiota-Derived Extracellular Vesicles, Immune Function, and Disease Development
Macia, L., Nanan, R. K. H., Beheshti, E. H., & Grau, G. E. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms21010107 · Cited by 240 · see citing works
Healthy Human Gastrointestinal Microbiome: Composition and Function After a Decade of Exploration
Ruan, W. H., Engevik, M. A., Spinler, J. K., & Versalovic, J. A. (2020) · Digestive Diseases and Sciences · doi:10.1007/s10620-020-06118-4 · Cited by 233 · see citing works
Hiippala, K., Barreto, G., Burrello, C., Díaz-Basabe, A., Suutarinen, M., Kainulainen, V., Bowers, J., Lemmer, D., Engelthaler, D., Eklund, K., et al. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.575455 · Cited by 206 · see citing works
Gut Microbiota Composition Is Related to AD Pathology
Verhaar, B. J. H., Hendriksen, H. M. A., de Leeuw, F. A., Doorduijn, A. S., van Leeuwenstijn, M. S. S. A., Teunissen, C. E., Barkhof, F., Scheltens, P., Kraaij, R., van Duijn, C. M., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2021.794519 · Cited by 237 · see citing works
Yi, D. Y., & Kim, S. (2021) · Nutrients · doi:10.3390/nu13093094 · Cited by 225 · see citing works
Álvarez-Villagómez, C. S., Badı́a, J., Bosch, M., Gíménez, R., & Baldomà, L. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01981 · Cited by 220 · see citing works
Turner, L., Bitto, N. J., Steer, D. L., Lo, C. Y.-W., D’Costa, K., Ramm, G., Shambrook, M., Hill, A. F., Ferrero, R. L., & Kaparakis‐Liaskos, M. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.01466 · Cited by 219 · see citing works
Emerging role of bacterial extracellular vesicles in cancer
Chronopoulos, A., & Kalluri, R. (2020) · Oncogene · doi:10.1038/s41388-020-01509-3 · Cited by 215 · see citing works
Extracellular Vesicle RNA: A Universal Mediator of Microbial Communication?
Tsatsaronis, J. A., Franch-Arroyo, S., Resch, U., & Charpentier, E. (2018) · Trends in Microbiology · doi:10.1016/j.tim.2018.02.009 · Cited by 210 · see citing works
Jones, E. J., Booth, C., Fonseca, S., Parker, A., Cross, K. L., Miquel-Clopés, A., Hautefort, I., Mayer, U., Wileman, T. E., Stentz, R., et al. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.00057 · Cited by 214 · see citing works
Wang, Y., Telesford, K. M., Ochoa‐Repáraz, J., Haque-Begum, S., Christy, M., Kasper, E. J., Wang, L., Wu, Y., Robson, S. C., Kasper, D. L., et al. (2014) · Nature Communications · doi:10.1038/ncomms5432 · Cited by 204 · see citing works
Wipperman, M. F., Fitzgerald, D. W., Juste, M. A. J., Taur, Y., Namasivayam, S., Sher, A., Bean, J. M., Bucci, V., & Glickman, M. S. (2017) · Scientific Reports · doi:10.1038/s41598-017-10346-6 · Cited by 206 · see citing works
Cohen, L. J., Cho, J. H., Gevers, D., & Chu, H. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.03.017 · Cited by 202 · see citing works
Cañas, M.-A., Fábrega, M.-J., Gíménez, R., Badı́a, J., & Baldomà, L. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00498 · Cited by 197 · see citing works
The extracellular RNA complement of Escherichia coli
Ghosal, A., Upadhyaya, B. B., Fritz, J. V., Heintz‐Buschart, A., Desai, M. S., Yusuf, D., Huang, D. Y. C., Baumuratov, A., Wang, K., Galas, D. J., et al. (2015) · MicrobiologyOpen · doi:10.1002/mbo3.235 · Cited by 195 · see citing works
Kashiwagi, I., Morita, R., Schichita, T., Komai, K., Saeki, K., Matsumoto, M., Takeda, K., Nomura, M., Hayashi, A., Kanai∥, T., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.06.010 · Cited by 194 · see citing works
Ageing of the gut microbiome: Potential influences on immune senescence and inflammageing
Conway, J., & Duggal, N. A. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101323 · Cited by 194 · see citing works
Outer Membrane Vesicles: Current Status and Future Direction of These Novel Vaccine Adjuvants
Tan, K., Li, R., Huang, X., & Liu, Q. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.00783 · Cited by 193 · see citing works
Kim, J., Jeun, E.-J., Hong, C., Kim, S. H., Jang, M. S., Lee, E.-J., Moon, S. J., Yun, C. H., Im, S.-H., Jeong, S.-G., et al. (2015) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2015.08.016 · Cited by 192 · see citing works
Regionalized Development and Maintenance of the Intestinal Adaptive Immune Landscape
Agace, W. W., & McCoy, K. D. (2017) · Immunity · doi:10.1016/j.immuni.2017.04.004 · Cited by 185 · see citing works
Ha, S., Wong, V. W., Zhang, X., & Yu, J. Q. (2024) · Gut · doi:10.1136/gutjnl-2024-332398 · Cited by 186 · see citing works
Wang, B., Zhang, L., Wang, Y., Dai, T., Qin, Z., Zhou, F., & Zhang, L. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00986-0 · Cited by 185 · see citing works
Hu, R., Lin, H., Wang, M., Zhao, Y., Liu, H., Min, Y., Yang, X., Gao, Y., & Yang, M. (2021) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-020-00532-4 · Cited by 185 · see citing works
Bittel, M., Reichert, P., Sarfati, I., Dressel, A., Leikam, S., Uderhardt, S., Stolzer, I., Phu, T. A., Ng, M., Vu, N. K., et al. (2021) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12159 · Cited by 180 · see citing works
Xu, J., Xu, J., Shi, T., Zhang, Y., Chen, F., Yang, C., Guo, X., Liu, G., Shao, D., Leong, K. W., et al. (2022) · Advanced Materials · doi:10.1002/adma.202207890 · Cited by 180 · see citing works
Mao, Y.-K., Kasper, D. L., Wang, B., Forsythe, P., Bienenstock, J., & Kunze, W. A. (2013) · Nature Communications · doi:10.1038/ncomms2478 · Cited by 178 · see citing works
Bacterial membrane vesicles: Biogenesis, immune regulation and pathogenesis
Pathirana, R. D., & Kaparakis‐Liaskos, M. (2016) · Cellular Microbiology · doi:10.1111/cmi.12658 · Cited by 178 · see citing works
The microbiota, immunoregulation, and mental health: implications for public health
Lowry, C. A., Smith, D. G., Siebler, P. H., Schmidt, D., Stamper, C. E., Hassell, J. E., Yamashita, P. S., Fox, J. H., Reber, S. O., Brenner, L. A., et al. (2016) · Current Environmental Health Reports · doi:10.1007/s40572-016-0100-5 · Cited by 172 · see citing works
Yan, F., & Polk, D. B. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01428 · Cited by 173 · see citing works
Ladinsky, M. S., Araújo, L. P., Zhang, X., Veltri, J., Galán-Díez, M., Soualhi, S., Lee, C., Irie, K., Pinker, E. Y., Narushima, S., et al. (2019) · Science · doi:10.1126/science.aat4042 · Cited by 170 · see citing works
Al‐Nedawi, K., Mian, M. F., Hossain, N., Karimi, K., Mao, Y., Forsythe, P., Min, K. K., Stanisz, A. M., Kunze, W. A., & Bienenstock, J. (2015) · The FASEB Journal · doi:10.1096/fj.14-259721 · Cited by 177 · see citing works
Development of novel nanoantibiotics using an outer membrane vesicle-based drug efflux mechanism
Huang, W., Zhang, Q., Li, W., Yuan, M., Zhou, J., Hua, L., Chen, Y., Ye, C., & Ma, Y. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.11.017 · Cited by 168 · see citing works
Roles of intestinal bacteroides in human health and diseases
Wang, C., Zhao, J., Zhang, H., Lee, Y. K., Zhai, Q., & Chen, W. (2020) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2020.1802695 · Cited by 166 · see citing works
A Host-Produced Autoinducer-2 Mimic Activates Bacterial Quorum Sensing
Ismail, A. S., Valastyan, J. S., & Bassler, B. L. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.02.020 · Cited by 160 · see citing works
Porter, N. T., Hryckowian, A. J., Merrill, B. D., Fuentes, J. J., Gardner, J. O., Glowacki, R. W. P., Singh, S., Crawford, R., Snitkin, E. S., Sonnenburg, J. L., et al. (2020) · Nature Microbiology · doi:10.1038/s41564-020-0746-5 · Cited by 155 · see citing works
Prokaryotic membrane vesicles: new insights on biogenesis and biological roles
Haurat, M. F., Elhenawy, W., & Feldman, M. F. (2014) · Biological Chemistry · doi:10.1515/hsz-2014-0183 · Cited by 157 · see citing works
The Environment of Regulatory T Cell Biology: Cytokines, Metabolites, and the Microbiome
Hoeppli, R. E., Wu, D., Cook, L., & Levings, M. K. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00061 · Cited by 157 · see citing works
Molina‐Tijeras, J. A., Gálvez, J., & Rodríguez‐Cabezas, M. E. (2019) · Nutrients · doi:10.3390/nu11051038 · Cited by 156 · see citing works
Disease Tolerance as an Inherent Component of Immunity
Martins, R., Carlos, A. R., Braza, F., Thompson, J. A., Bastos-Amador, P., Ramos, S., & Soares, M. P. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041739 · Cited by 149 · see citing works
Choi, J., Kim, Y., & Han, P. (2019) · Experimental Neurobiology · doi:10.5607/en.2019.28.2.158 · Cited by 154 · see citing works
Fantastic voyage: the journey of intestinal microbiota-derived microvesicles through the body
Stentz, R., Carvalho, A. L., Jones, E. J., & Carding, S. R. (2018) · Biochemical Society Transactions · doi:10.1042/bst20180114 · Cited by 153 · see citing works
Shen, Q., Huang, Z., Yao, J., & Jin, Y. (2021) · Journal of Advanced Research · doi:10.1016/j.jare.2021.07.002 · Cited by 160 · see citing works
Villena, J., & Kitazawa, H. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00512 · Cited by 153 · see citing works
- Authors
- Shen, Y., Torchia, M. L. G., Lawson, G. W., Karp, C. L., Ashwell, J. D., & Mazmanian, S. K.
- Affiliations
- California Institute of Technology (US)
- National Institutes of Health (US)
- University of California, Los Angeles (US)
- Cincinnati Children's Hospital Medical Center (US)
- Corresponding author
- Mazmanian, Sarkis K.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 12
- Issue
- 4
- Pages
- 509-520
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC3895402
- OpenAlex
- W2051349444
- Cited by
- 714
- References
- 41
- Citations by year
- 2026: 59 · 2025: 84 · 2024: 60 · 2023: 61 · 2022: 69 · 2021: 83 · 2020: 61 · 2019: 48 · 2018: 34 · 2017: 40 · 2016: 30 · 2015: 27 · 2014: 33 · 2013: 23 · 2012: 1
- FWCI
- 11.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (T32GM007616, GM007616)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 078938, R01DK078938, R21DK083633, R56DK078938)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- outer membrane vesicles, Bacteroides fragilis, capsular polysaccharide, commensal bacteria, regulatory T cells, dendritic cells, TLR2, GADD45A, experimental colitis, mucosal tolerance, immunomodulation, interkingdom communication, gut microbiota, anti-inflammatory cytokines
- MeSH terms
- GADD45 Proteins, Animals, Bacteroides fragilis, Dendritic Cells, Immunologic Factors, Mice, Inbred BALB C, Mice, Inbred C57BL, Nuclear Proteins, Polysaccharides, Bacterial, Cytokines, Mice, Knockout, Cell Cycle Proteins, Gene Expression Profiling, T-Lymphocytes, Regulatory, Toll-Like Receptor 2, Mice, Exosomes
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