{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:51:04Z","timestamp":1791384664221,"version":"4.3.3"},"reference-count":164,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T00:00:00Z","timestamp":1606176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The discovery of the microbiota-gut-brain axis has revolutionized our understanding of systemic influences on brain function and may lead to novel therapeutic approaches to neurodevelopmental and mood disorders. A parallel revolution has occurred in the field of intercellular communication, with the realization that endosomes, and other extracellular vesicles, rival the endocrine system as regulators of distant tissues. These two paradigms shifting developments come together in recent observations that bacterial membrane vesicles contribute to inter-kingdom signaling and may be an integral component of gut microbe communication with the brain. In this short review we address the current understanding of the biogenesis of bacterial membrane vesicles and the roles they play in the survival of microbes and in intra and inter-kingdom communication. We identify recent observations indicating that bacterial membrane vesicles, particularly those derived from probiotic organisms, regulate brain function. We discuss mechanisms by which bacterial membrane vesicles may influence the brain including interaction with the peripheral nervous system, and modulation of immune activity. We also review evidence suggesting that, unlike the parent organism, gut bacteria derived membrane vesicles are able to deliver cargo, including neurotransmitters, directly to the central nervous system and may thus constitute key components of the microbiota-gut-brain axis.<\/jats:p>","DOI":"10.3390\/ijms21238899","type":"journal-article","created":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T09:06:28Z","timestamp":1606208788000},"page":"8899","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":133,"title":["A Budding Relationship: Bacterial Extracellular Vesicles in the Microbiota-Gut-Brain Axis"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7981-5285","authenticated-orcid":false,"given":"Sandor","family":"Haas-Neill","sequence":"first","affiliation":[{"name":"McMaster Brain-Body Institute, The Research Institute of St. Joseph\u2019s Hamilton, Hamilton, ON L8N 4A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Forsythe","sequence":"additional","affiliation":[{"name":"McMaster Brain-Body Institute, The Research Institute of St. Joseph\u2019s Hamilton, Hamilton, ON L8N 4A6, Canada"},{"name":"Firestone Institute for Respiratory Health, St. Joseph\u2019s Healthcare and Department of Medicine, McMaster University, Hamilton, ON L8N 4A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12916-016-0604-8","article-title":"Moody microbes or fecal phrenology: What do we know about the microbiota-gut-brain axis?","volume":"14","author":"Forsythe","year":"2016","journal-title":"BMC Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1113\/jphysiol.2004.063388","article-title":"Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice","volume":"558","author":"Sudo","year":"2004","journal-title":"J. Physiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"16050","DOI":"10.1073\/pnas.1102999108","article-title":"Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve","volume":"108","author":"Bravo","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14785\/lymphosign-2019-0018","article-title":"Microbiota-immune interactions: From gut to brain","volume":"7","author":"Stokes","year":"2020","journal-title":"Lymphosign J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/j.physbeh.2006.06.019","article-title":"Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium","volume":"3","author":"Lyte","year":"2006","journal-title":"Physiol. Behav."},{"key":"ref_6","first-page":"G661","article-title":"Posttraumatic stress disorder is associated with altered gut microbiota that modulates cognitive performance in veterans with cirrhosis","volume":"317","author":"Bajaj","year":"2019","journal-title":"Am. Psysiological Soc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2045125319859963","DOI":"10.1177\/2045125319859963","article-title":"Gut feeling: Randomized controlled trials of probiotics for the treatment of clinical depression: Systematic review and meta-analysis","volume":"9","author":"Nikolova","year":"2019","journal-title":"Ther. Adv. Psychopharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1097\/01.mpg.0000226376.95623.9f","article-title":"Nutritional approach to restore impaired intestinal barrier function and growth after neonatal stress in rats","volume":"43","author":"Bergonzelli","year":"2006","journal-title":"J. Pediatric Gastroenterol. Nutr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.biopsych.2008.06.026","article-title":"Early life stress alters behavior, immunity, and microbiota in rats: Implications for irritable bowel syndrome and psychiatric illnesses","volume":"65","author":"Marchesi","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1016\/j.neuroscience.2010.08.005","article-title":"Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression","volume":"170","author":"Desbonnet","year":"2010","journal-title":"Neuroscience"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7735","DOI":"10.1038\/ncomms8735","article-title":"Microbiota and host determinants of behavioural phenotype in maternally separated mice","volume":"6","author":"Blennerhassett","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"49","DOI":"10.3389\/fnins.2018.00049","article-title":"The vagus nerve at the interface of the microbiota-gut-brain axis","volume":"12","author":"Bonaz","year":"2018","journal-title":"Front. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.bbi.2007.08.009","article-title":"Campylobacter jejuni infection increases anxiety-like behaviour in the holeboard: Possible anatomical substrates for viscerosensory modulation of exploratory behavior","volume":"22","author":"Goehler","year":"2008","journal-title":"Brain Behav. Immun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/nmo.12049","article-title":"The microbiome is essential for normal gut intrinsic primary afferent neuron excitability in the mouse","volume":"25","author":"Mao","year":"2013","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1111\/j.1582-4934.2009.00686.x","article-title":"Lactobacillus reuteri enhances excitability of colonic AH neurons by inhibiting calcium-dependent potassium channel opening","volume":"13","author":"Kunze","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/nrgastro.2013.29","article-title":"Extrinsic primary afferent signaling in the gut","volume":"10","author":"Brookes","year":"2013","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1152\/ajpgi.00128.2012","article-title":"Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents","volume":"304","author":"Wang","year":"2013","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/978-1-4939-0897-4_5","article-title":"Vagal pathways for microbiome-brain-gut axis communication","volume":"17","author":"Forsythe","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1111\/j.1365-2982.2011.01796.x","article-title":"The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication","volume":"23","author":"Bercik","year":"2011","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.neuron.2018.11.018","article-title":"Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder","volume":"101","author":"Sgritta","year":"2019","journal-title":"Neuron"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/nmo.12540","article-title":"Vagotomy prevents the effect of probiotics on caspase activity in a model of postmyocardial infarction depression","volume":"27","author":"Malick","year":"2015","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00441-007-0413-7","article-title":"Vagal innervation of intestines: Afferent pathways mapped with new en bloc horseradish peroxidase adaptation","volume":"329","author":"Wang","year":"2007","journal-title":"Cell Tissue Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1016\/S0016-5085(00)70373-8","article-title":"Serotonin released from intestinal enterochromaffin cells mediates luminal non-cholecystokinin-stimulated pancreatic secretion in rats","volume":"118","author":"Li","year":"2000","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1053\/j.gastro.2004.10.043","article-title":"Gastrointestinal hormones and food intake","volume":"128","author":"Strader","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4453","DOI":"10.4049\/jimmunol.174.8.4453","article-title":"TLR signaling in the gut in health and disease","volume":"174","author":"Abreu","year":"2005","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"G1770-83","DOI":"10.1152\/ajpgi.00249.2006","article-title":"Enteroendocrine cells express functional Toll-like receptors","volume":"292","author":"Bogunovic","year":"2007","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3064","DOI":"10.1096\/fj.13-245282","article-title":"The gut-brain axis rewired: Adding a functional vagal nicotinic \u201csensory synapse\u201d","volume":"28","author":"Mao","year":"2014","journal-title":"FASEB J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ynstr.2016.03.001","article-title":"The microbiome: A key regulator of stress and neuroinflammation","volume":"4","author":"Rea","year":"2016","journal-title":"Neurobiol. Stress"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.neuroscience.2015.09.033","article-title":"Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress","volume":"310","author":"Liang","year":"2015","journal-title":"Neuroscience"},{"key":"ref_30","first-page":"1","article-title":"Stress induces endotoxemia and low-grade inflammation by increasing barrier permeability","volume":"6","author":"Pruimboom","year":"2015","journal-title":"Front. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3109\/08820131003667978","article-title":"Immunomodulation by commensal and probiotic bacteria","volume":"39","author":"Forsythe","year":"2010","journal-title":"Immunol. Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1038\/nrmicro2876","article-title":"The interplay between the intestinal microbiota and the brain","volume":"10","author":"Collins","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.bbi.2020.04.014","article-title":"CD4 + CD25 + T Cells are Essential for Behavioral Effects of Lactobacillus rhamnosus JB-1 in Male BALB\/c mice","volume":"88","author":"Liu","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nrn2297","article-title":"From inflammation to sickness and depression: When the immune system subjugates the brain","volume":"9","author":"Dantzer","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1016\/j.celrep.2016.04.074","article-title":"Ly6C(hi) Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis","volume":"15","author":"Mattei","year":"2016","journal-title":"Cell Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/npp.2016.102","article-title":"Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal","volume":"42","author":"Weber","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.cell.2014.03.011","article-title":"Role of the microbiota in immunity and inflammation","volume":"157","author":"Belkaid","year":"2014","journal-title":"Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"428","DOI":"10.3389\/fphys.2019.00428","article-title":"The Influence of the Gut Microbiome on Host Metabolism Through the Regulation of Gut Hormone Release","volume":"10","author":"Martin","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1210\/me.2014-1108","article-title":"Minireview: Gut Microbiota: The Neglected Endocrine Organ","volume":"28","author":"Clarke","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1016\/j.psyneuen.2012.03.007","article-title":"Regulation of the stress response by the gut microbiota: Implications for psychoneuroendocrinology","volume":"37","author":"Dinan","year":"2012","journal-title":"Phychoneuroendocrinology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/nn.4030","article-title":"Host microbiota constantly control maturation and function of microglia in the CNS","volume":"18","author":"Erny","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_42","first-page":"5","article-title":"Gut Microbiota and the Neuroendocrine System","volume":"15","author":"Farzi","year":"2018","journal-title":"Neurother. J. Am. Soc. Exp. Neurother."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1016\/j.tins.2016.09.002","article-title":"Psychobiotics and the Manipulation of Bacteria-Gut-Brain Signals","volume":"39","author":"Sarkar","year":"2016","journal-title":"Trends Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/bies.201100024","article-title":"Probiotics function mechanistically as delivery vehicles for neuroactive compounds: Microbial endocrinology in the design and use of probiotics","volume":"33","author":"Lyte","year":"2011","journal-title":"BioEssays"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1038\/nrn3346","article-title":"Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour","volume":"13","author":"Cryan","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.biopsych.2013.05.001","article-title":"Psychobiotics: A novel class of psychotropic","volume":"74","author":"Dinan","year":"2013","journal-title":"Biol. Psychiatry"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3389\/fphar.2010.00124","article-title":"A Gut Feeling about GABA: Focus on GABA(B) Receptors","volume":"1","author":"Hyland","year":"2010","journal-title":"Front. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1093\/femsre\/fuy042","article-title":"Extracellular membrane vesicles in the three domains of life and beyond","volume":"43","author":"Gill","year":"2019","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/s41579-018-0112-2","article-title":"Types and origins of bacterial membrane vesicles","volume":"17","author":"Toyofuku","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1002\/smll.201401803","article-title":"In vivo kinetic biodistribution of nano-sized outer membrane vesicles derived from bacteria","volume":"11","author":"Jang","year":"2015","journal-title":"Small"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.3389\/fmicb.2018.01502","article-title":"Gram-positive bacterial extracellular vesicles and their impact on health and disease","volume":"9","author":"Liu","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1146\/annurev.micro.091208.073413","article-title":"Biological Functions and Biogenesis of Secreted Bacterial Outer Membrane Vesicles","volume":"64","author":"Kulp","year":"2010","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e00207-16","DOI":"10.1128\/mBio.00207-16","article-title":"A two-component regulatory system impacts extracellular membrane-derived vesicle production in Group a Streptococcus","volume":"7","author":"Resch","year":"2016","journal-title":"MBio"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3389\/fmicb.2019.03026","article-title":"Cracking Open Bacterial Membrane Vesicles","volume":"10","author":"Nagakubo","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/s41467-017-00492-w","article-title":"Prophage-triggered membrane vesicle formation through peptidoglycan damage in Bacillus subtilis","volume":"8","author":"Toyofuku","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"e1439","DOI":"10.1128\/AAC.01439-18","article-title":"Antibiotics stimulate formation of vesicles in staphylococcus aureus in both phage-dependent and -independent fashions and via different routes","volume":"63","author":"Andreoni","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1038\/s41467-018-03847-z","article-title":"Release of Staphylococcus aureus extracellular vesicles and their application as a vaccine platform","volume":"9","author":"Wang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.3389\/fmicb.2017.02440","article-title":"In Silico analysis of the small molecule content of outer membrane vesicles produced by Bacteroides thetaiotaomicron indicates an extensive metabolic link between microbe and host","volume":"8","author":"Bryant","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1074\/jbc.M307628200","article-title":"Incorporation of Heterologous Outer Membrane and Periplasmic Proteins into Escherichia coli Outer Membrane Vesicles","volume":"279","author":"Nicole","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nri3837","article-title":"Immune modulation by bacterial outer membrane vesicles","volume":"15","author":"Ferrero","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2355","DOI":"10.1128\/JB.01493-14","article-title":"Streptococcus mutans extracellular DNA is upregulated during growth in biofilms, actively released via membrane vesicles, and influenced by components of the protein secretion machinery","volume":"196","author":"Liao","year":"2014","journal-title":"J. Bacteriol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1096\/fj.14-259721","article-title":"Gut commensal microvesicles reproduce parent bacterial signals to host immune and enteric nervous systems","volume":"29","author":"Mian","year":"2015","journal-title":"FASEB J."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Uddin, J., Dawan, J., Jeon, G., Yu, T., He, X., and Ahn, J. (2020). The Role of Bacterial Membrane Vesicles in theDissemination of Antibiotic Resistance and asPromising Carriers for Therapeutic Agent Delivery. Microorganisms, 8.","DOI":"10.3390\/microorganisms8050670"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/j.1365-2958.2006.05522.x","article-title":"Release of outer membrane vesicles by Gram-negative bacteria is a novel envelope stress response","volume":"63","author":"McBroom","year":"2007","journal-title":"Mol. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1100\/2012\/402919","article-title":"Vesiculation from Pseudomonas aeruginosa under SOS","volume":"2012","author":"Maredia","year":"2012","journal-title":"Sci. World J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1128\/JB.02267-12","article-title":"Stress-induced outer membrane vesicle production by Pseudomonas aeruginosa","volume":"195","author":"MacDonald","year":"2013","journal-title":"J. Bacteriol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/JB.00740-17","article-title":"Outer membrane vesicles facilitate trafficking of the hydrophobic signaling molecule CAI-1 between Vibrio harveyi cells","volume":"200","author":"Brameyer","year":"2018","journal-title":"J. Bacteriol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/0005-2736(78)90081-0","article-title":"Release of a special fraction of the outer membrane from both growing and phage T4-infected Escherichia coli B","volume":"514","author":"Loeb","year":"1978","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1111\/j.1472-4669.2008.00158.x","article-title":"Redox-reactive membrane vesicles produced by Shewanella","volume":"6","author":"Gorby","year":"2008","journal-title":"Geobiology"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1038\/nature03925","article-title":"Membrane vesicles traffic signals and facilitate group activities in a prokaryote","volume":"437","author":"Mashburn","year":"2005","journal-title":"Nature"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1039\/b803796p","article-title":"Quorum sensing by 2-alkyl-4-quinolones in Pseudomonas aeruginosa and other bacterial species","volume":"4","author":"Dubern","year":"2008","journal-title":"Mol. Biosyst."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"5945","DOI":"10.1128\/JB.00257-06","article-title":"Membrane vesicles: An overlooked component of the matrices of biofilms","volume":"188","author":"Schooling","year":"2006","journal-title":"J. Bacteriol."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Yonezawa, H., Osaki, T., Kurata, S., Fukuda, M., Kawakami, H., Ochiai, K., Hanawa, T., and Kamiya, S. (2009). Outer membrane vesicles of Helicobacter pylori TK1402 are involved in biofilm formation. BMC Microbiol., 9.","DOI":"10.1186\/1471-2180-9-197"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6927","DOI":"10.1073\/pnas.80.22.6927","article-title":"Transformasomes: Specialized membranous structures that protect DNA during Haemophilus transformation","volume":"80","author":"Kahn","year":"1983","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2985","DOI":"10.1128\/JB.182.10.2985-2988.2000","article-title":"Sulfolobicins, specific proteinaceous toxins produced by strains of the extremely thermophilic archaeal genus Sulfolobus","volume":"182","author":"Prangishvili","year":"2000","journal-title":"J. Bacteriol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1042\/BST20180114","article-title":"Fantastic voyage: The journey of intestinal microbiota-derived microvesicles through the body","volume":"46","author":"Stentz","year":"2018","journal-title":"Biochem. Soc. Trans."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.3389\/fmicb.2017.01053","article-title":"Outer Membrane Vesicles (OMVs) of gram-negative bacteria: A perspective update","volume":"8","author":"Jan","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"13412","DOI":"10.1096\/fj.201901575R","article-title":"Extracellular RNAs in periodontopathogenic outer membrane vesicles promote TNF-\u03b1 production in human macrophages and cross the blood-brain barrier in mice","volume":"33","author":"Han","year":"2019","journal-title":"FASEB J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2645","DOI":"10.1101\/gad.1299905","article-title":"Bacterial outer membrane vesicles and the host-pathogen interaction","volume":"19","author":"Kuehn","year":"2005","journal-title":"Genes Dev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"369","DOI":"10.5607\/en.2017.26.6.369","article-title":"Metagenome analysis of bodily microbiota in a mouse model of Alzheimer disease using bacteria-derived membrane vesicles in blood","volume":"26","author":"Park","year":"2017","journal-title":"Exp. Neurobiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1128\/JCM.39.5.1956-1959.2001","article-title":"Does Blood of Healthy Subjects Contain Bacterial Ribosomal DNA?","volume":"39","author":"Nikkari","year":"2001","journal-title":"J. Clin. Microbiol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1111\/trf.13477","article-title":"Comprehensive description of blood microbiome from healthy donors assessed by 16S targeted metagenomic sequencing","volume":"56","author":"Valle","year":"2016","journal-title":"Transfusion"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1007\/s10096-016-2805-7","article-title":"Comprehensive detection and identification of bacterial DNA in the blood of patients with sepsis and healthy volunteers using next-generation sequencing method\u2014The observation of DNAemia","volume":"36","author":"Gosiewski","year":"2017","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1007\/s11481-013-9462-8","article-title":"Evidence for a dysregulated immune system in the etiology of psychiatric disorders","volume":"8","author":"Gibney","year":"2013","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1111\/cei.13334","article-title":"The immune system and psychiatric disease: A basic science perspective","volume":"197","author":"Bennett","year":"2019","journal-title":"Clin. Exp. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-19276-3","article-title":"First description of behavior and immune system relationship in fish","volume":"8","author":"Kirsten","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1002\/hipo.10135","article-title":"Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity","volume":"13","author":"Avital","year":"2003","journal-title":"Hippocampus"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1084\/jem.20091419","article-title":"Regulation of learning and memory by meningeal immunity: A key role for IL-4","volume":"207","author":"Derecki","year":"2010","journal-title":"J. Exp. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1073\/pnas.0809479105","article-title":"Brain mast cells link the immune system to anxiety-like behavior","volume":"105","author":"Nautiyal","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nature18626","article-title":"Unexpected role of interferon-\u03b3 in regulating neuronal connectivity and social behavior","volume":"535","author":"Filiano","year":"2013","journal-title":"Nature"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1007\/s10519-015-9714-x","article-title":"IL-4 Knock Out Mice Display Anxiety-Like Behavior","volume":"45","author":"Moon","year":"2015","journal-title":"Behav. Genet."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.iac.2009.02.002","article-title":"Cytokine, sickness behavior, and depression","volume":"29","author":"Dantzer","year":"2009","journal-title":"Immunol. Allergy Clin. North Am."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1038\/sj.npp.1301649","article-title":"Aging exacerbates depressive-like behavior in mice in response to acti- vation of the peripheral innate immune system","volume":"33","author":"Godbout","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/nri.2015.5","article-title":"The role of inflammation in depression: From evolutionary imperative to modern treatment target","volume":"16","author":"Miller","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1046\/j.1532-5415.2002.50619.x","article-title":"Cytokines and cognition--the case for a head-to-toe inflammatory paradigm","volume":"50","author":"Wilson","year":"2002","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jad.2009.10.018","article-title":"Altered expression of CD4(+)CD25(+) regulatory T cells and its 5-HT(1a) receptor in patients with major depression disorder","volume":"124","author":"Li","year":"2010","journal-title":"J. Affect. Disord."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1016\/j.bbi.2009.07.003","article-title":"Substantial reduction of na\u00efve and regulatory T cells following traumatic stress","volume":"23","author":"Sommershof","year":"2009","journal-title":"Brain Behav. Immun."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Kim, S.J., Lee, H., Lee, G., Oh, S.J., Shin, M.K., Shim, I., and Bae, H. (2012). Cd4+cd25+ regulatory t cell depletion modulates anxiety and depression-like behaviors in mice. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042054"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Molina-Tijeras, J.A., G\u00e1lvez, J., and Rodr\u00edguez-Cabezas, M.E. (2019). The immunomodulatory properties of extracellular vesicles derived from probiotics: A novel approach for the management of gastrointestinal diseases. Nutrients, 11.","DOI":"10.3390\/nu11051038"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1038\/nrmicro2297","article-title":"Host interactions of probiotic bacterial surface molecules: Comparison with commensals and pathogens","volume":"8","author":"Leeber","year":"2010","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.jss.2013.05.035","article-title":"Outer membrane vesicles from pathogenic bacteria initiate an inflammatory response in human endothelial cells","volume":"184","author":"Soult","year":"2013","journal-title":"J. Surg. Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1111\/j.1462-5822.2009.01404.x","article-title":"Bacterial membrane vesicles deliver peptidoglycan to NOD1 in epithelial cells","volume":"12","author":"Kaparakis","year":"2010","journal-title":"Cell Microbiol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Meganathan, V., Moyana, R., Natarajan, K., Kujur, W., Kusampudi, S., Mulik, S., and Boggaram, V. (2020). Bacterial extracellular vesicles isolated from organic dust induce neutrophilic inflammation in the lung. Am. J. Physiol. Lung Cell. Mol. Physiol.","DOI":"10.1152\/ajplung.00107.2020"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.ijmm.2018.06.004","article-title":"Enterohemorrhagic Escherichia coli O157 outer membrane vesicles induce interleukin 8 production in human intestinal epithelial cells by signaling via Toll-like receptors TLR4 and TLR5 and activation of the nuclear factor NF-\u03baB","volume":"308","author":"Bielaszewska","year":"2018","journal-title":"Int. J. Med Microbiol."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"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., and Myung, S.J. (2013). Extracellular vesicles derived from gut microbiota, especially Akkermansia muciniphila, protect the progression of dextran sulfate sodium-induced colitis. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0076520"},{"key":"ref_106","first-page":"57","article-title":"Induction effects of bacteroides fragilis derived outer membrane vesicles on toll like receptor 2, toll like receptor 4 genes expression and cytokines concentration in human intestinal epithelial cells","volume":"21","author":"Badi","year":"2019","journal-title":"Cell J."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.chom.2012.08.004","article-title":"Outer Membrane Vesicles of a Human Commensal Mediate Immune Regulation and Disease Protection","volume":"12","author":"Shen","year":"2012","journal-title":"Cell Host Microbe"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1126\/science.aad9948","article-title":"Gene-Microbiota Interactions Contribute to the Pathogenesis of Inflammatory Bowel Disease","volume":"352","author":"Hiutung","year":"2016","journal-title":"Science"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0047556","article-title":"A Lactobacillus rhamnosus Strain Induces a Heme Oxygenase Dependent Increase in Foxp3+ Regulatory T Cells","volume":"7","author":"Karimi","year":"2012","journal-title":"PLoS ONE"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/19490976.2017.1344810","article-title":"Outer membrane vesicles blebbing contributes to B. vulgatus mpk-mediated immune response silencing","volume":"9","author":"Maerz","year":"2018","journal-title":"Gut Microbes"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.3389\/fmicb.2017.01274","article-title":"Intestinal Anti-inflammatory Effects of Outer Membrane Vesicles from Escherichia coli Nissle 1917 in DSS-Experimental Colitis in Mice","volume":"8","author":"Algieri","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_112","first-page":"705","article-title":"Activation of Immune and Defense Responses in the Intestinal Mucosa by Outer Membrane Vesicles of Commensal and Probiotic Escherichia coli Strains","volume":"7","author":"Aguilera","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"8662","DOI":"10.3168\/jds.2018-15014","article-title":"Therapeutic effects of kefir grain Lactobacillus-derived extracellular vesicles in mice with 2,4,6-trinitrobenzene sulfonic acid-induced inflammatory bowel disease","volume":"101","author":"Seo","year":"2018","journal-title":"J. Dairy Sci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"23","DOI":"10.12938\/bmfh.18-015","article-title":"IgA-enhancing effects of membrane vesicles derived from Lactobacillus sakei subsp. sakei NBRC15893","volume":"38","author":"Miyoshi","year":"2019","journal-title":"Biosci. Microbiota Food Health"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.jaci.2015.08.016","article-title":"Extracellular vesicle-derived protein from Bifidobacterium longum alleviates food allergy through mast cell suppression","volume":"137","author":"Kim","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.1128\/AEM.07581-11","article-title":"Interaction of Bifidobacterium bifidum LMG13195 with HT29 cells influences regulatory-T-cell-associated chemokine receptor expression","volume":"78","author":"Margolles","year":"2012","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_117","first-page":"108067","article-title":"The vagus nerve is necessary for the rapid and widespread neuronal activation in the brain following oral administration of psychoactive bacteria","volume":"15","author":"West","year":"2020","journal-title":"Neuropharmacology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.autneu.2009.07.007","article-title":"Gut Chemosensing: Interactions between Gut Endocrine Cells and Visceral Afferents","volume":"153","author":"Raybould","year":"2010","journal-title":"Auton. Neurosci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s40168-020-00881-2","article-title":"The extracellular vesicle of gut microbial Paenalcaligenes hominis is a risk factor for vagus nerve-mediated cognitive impairment","volume":"8","author":"Lee","year":"2020","journal-title":"Microbiome"},{"key":"ref_120","unstructured":"Lyte, M., and Freestone, P.P.E. (2020). Evolutionary Considerations of Neurotransmitters in Microbial, Plant, and Animal Cells. Microbial Endocrinology: Interkingdom Signaling in Infectious Disease and Health, Springer."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3389\/fnins.2019.01361","article-title":"Antidepressive Mechanisms of Probiotics and Their Therapeutic Potential","volume":"13","author":"Yong","year":"2020","journal-title":"Front. Neurosci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"5008","DOI":"10.1038\/s41598-017-05264-6","article-title":"Outer membrane vesicles secreted by pathogenic and nonpathogenic Bacteroides fragilis represent different metabolic activities","volume":"7","author":"Zakharzhevskaya","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.bcp.2006.12.002","article-title":"Histamine in the brain: Beyond sleep and memory","volume":"73","author":"Passani","year":"2007","journal-title":"Biochem. Pharmacol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.neuropharm.2011.08.040","article-title":"The GABA system in anxiety and depression and its therapeutic potential","volume":"62","year":"2012","journal-title":"Neuropharmacology"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3389\/fncel.2017.00305","article-title":"From Serotonin to Neuroplasticity: Evolvement of Theories for Major Depressive Disorder","volume":"11","author":"Liu","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"557928","DOI":"10.3389\/fneur.2020.557928","article-title":"From the Gut to the Brain and Back: Therapeutic Approaches for the Treatment of Network Dysfunction in Parkinson\u2019s Disease","volume":"11","author":"Paolone","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1177\/1535370220923585","article-title":"Microbial extracellular RNAs and their roles in human diseases","volume":"245","author":"Lee","year":"2020","journal-title":"Exp. Biol. Med."},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Koeppen, K., Hampton, T.H., Jarek, M., Scharfe, M., Gerber, S.A., Mielcarz, D.W., Demers, E.G., Dolben, E.L., Hammond, J.H., and Hogan, D.A. (2016). A Novel Mechanism of Host-Pathogen Interaction through sRNA in Bacterial Outer Membrane Vesicles. PLoS Pathogogy, 12.","DOI":"10.1371\/journal.ppat.1005672"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1177\/0022034516685071","article-title":"Secretable Small RNAs via Outer Membrane Vesicles in Periodontal Pathogens","volume":"96","author":"Choi","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.tim.2016.05.005","article-title":"How Our Other Genome Controls Our Epi-Genome","volume":"24","author":"Celluzzi","year":"2016","journal-title":"Trends Microbiol."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Zimmer-Bensch, G. (2019). Emerging Roles of Long Non-Coding RNAs as Drivers of Brain Evolution. Cells, 8.","DOI":"10.20944\/preprints201911.0031.v1"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1134\/S0006297920090023","article-title":"Epigenetic Regulation as a Basis for Long-Term Changes in the Nervous System: In Search of Specificity Mechanisms","volume":"85","author":"Borodinova","year":"2020","journal-title":"Biochemistry (Moscow)"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3389\/fnagi.2017.00195","article-title":"16S rRNA next generation sequencing analysis shows bacteria in Alzheimer\u2019s Post-Mortem Brain","volume":"9","author":"Emery","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1111\/j.1532-5415.2012.04064.x","article-title":"Dentition, dental health habits, and dementia: The Leisure World cohort study","volume":"60","author":"White","year":"2012","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jneuroim.2009.08.013","article-title":"TNF-\u03b1 and antibodies to periodontal bacteria discriminate between Alzheimer\u2019s disease patients and normal subjects","volume":"216","author":"Kamer","year":"2009","journal-title":"J. Neuroimmunol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1212\/WNL.0000000000003391","article-title":"Gram-negative bacterial molecules associate with Alzheimer disease pathology","volume":"87","author":"Zhan","year":"2016","journal-title":"Neurology"},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Branton, W.G., Ellestad, K.K., Maingat, F., Wheatley, B.M., Rud, E., Warren, R.L., Holt, R.A., Surette, M.G., and Power, C. (2013). Brain Microbial Populations in HIV\/AIDS: \u03b1-Proteobacteria Predominate Independent of Host Immune Status. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054673"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"eaau3333","DOI":"10.1126\/sciadv.aau3333","article-title":"Porphyromonas gingivalis in Alzheimer\u2019s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors","volume":"5","author":"Dominy","year":"2019","journal-title":"Sci. Adv."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2559","DOI":"10.1128\/iai.57.8.2559-2562.1989","article-title":"Haemophilus influenzae Outer Membrane Vesicle-Induced Blood-Brain Barrier Permeability during Experimental Meningitis","volume":"57","author":"Wispelwey","year":"1989","journal-title":"Infect. Immun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1172\/JCI112407","article-title":"Morphologic alterations of the blood-brain barrier with experimental meningitis in the rat. Temporal sequence and role of encapsulation","volume":"77","author":"Quagliarello","year":"1986","journal-title":"J. Clin. Investig."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"158","DOI":"10.5607\/en.2019.28.2.158","article-title":"Extracellular vesicles derived from Lactobacillus plantarum increase BDNF expression in cultured hippocampal neurons and produce antidepressant-like effects in mice","volume":"28","author":"Choi","year":"2019","journal-title":"Exp. Neurobiol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nrm.2017.125","article-title":"Shedding light on the cell biology of extracellular vesicles","volume":"19","author":"Raposo","year":"2018","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s00401-018-1868-1","article-title":"Alzheimer\u2019s disease pathology propagation by exosomes containing toxic amyloid-beta oligomers","volume":"136","author":"Sardar","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1080\/08923973.2019.1650371","article-title":"The multiple roles of exosomes in Parkinson\u2019s disease: An overview","volume":"41","author":"Porro","year":"2019","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"15699","DOI":"10.1074\/jbc.M112.425066","article-title":"Mutant copper-zinc superoxide dismutase (SOD1) induces protein secretion pathway alterations and exosome release in astrocytes: Implications for disease spreading and motor neuron pathology in amyotrophic lateral sclerosis","volume":"288","author":"Basso","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.jconrel.2020.09.019","article-title":"ADSCs-derived extracellular vesicles alleviate neuronal damage, promote neurogenesis and rescue memory loss in mice with Alzheimer\u2019s disease","volume":"327","author":"Ma","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1002\/sctm.18-0162","article-title":"Intranasal Administration of Extracellular Vesicles Derived from Human Teeth Stem Cells Improves Motor Symptoms and Normalizes Tyrosine Hydroxylase Expression in the Substantia Nigra and Striatum of the 6-Hydroxydopamine-Treated Rats","volume":"8","author":"Narbute","year":"2019","journal-title":"Stem Cells Transl. Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"e00705-18","DOI":"10.1128\/IAI.00705-18","article-title":"Induction of Inflammatory Responses in Splenocytes by Exosomes Released from Intestinal Epithelial Cells following Cryptosporidium parvum Infection","volume":"87","author":"Wang","year":"2019","journal-title":"Infection Immun."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1097\/TA.0000000000001748","article-title":"Gut epithelial cell-derived exosomes trigger posttrauma immune dysfunction","volume":"84","author":"Kojima","year":"2018","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.cell.2015.02.047","article-title":"Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis","volume":"161","author":"Yano","year":"2015","journal-title":"Cell"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/srep17324","article-title":"Escherichia coli Nissle 1917 enhances bioavailability of serotonin in gut tissues through modulation of synthesis and clearance","volume":"5","author":"Nzakizwanayo","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.molmet.2018.03.004","article-title":"Enterochromaffin 5-HT cells\u2014A major target for GLP-1 and gut microbial metabolites","volume":"11","author":"Lund","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"5959","DOI":"10.1113\/jphysiol.2013.259796","article-title":"Identification of unique release kinetics of serotonin from guinea-pig and human enterochromaffin cells","volume":"591","author":"Raghupathi","year":"2013","journal-title":"J. Physiol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/s41398-019-0459-9","article-title":"The emerging role of exosomes in mental disorders","volume":"9","author":"Saeedi","year":"2019","journal-title":"Transl. Psychiatry"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s40478-017-0470-4","article-title":"Transmission of \u03b1-synuclein-containing erythrocyte-derived extracellular vesicles across the blood-brain barrier via adsorptive mediated transcytosis: Another mechanism for initiation and progression of Parkinson\u2019s disease?","volume":"5","author":"Matsumoto","year":"2017","journal-title":"Acta Neuropathol. Commun."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2003","DOI":"10.1007\/s11095-014-1593-y","article-title":"Exosome Delivered Anticancer Drugs Across the Blood-Brain Barrier for Brain Cancer Therapy in Danio Rerio","volume":"32","author":"Yang","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nature15756","article-title":"Tumour exosome integrins determine organotropic metastasis","volume":"527","author":"Hoshino","year":"2015","journal-title":"Nature"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.1016\/j.biocel.2012.06.018","article-title":"Toward tailored exosomes: The exosomal tetraspanin web contributes to target cell selection","volume":"44","author":"Rana","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1007\/s00018-017-2664-0","article-title":"Amyloid precursor protein products concentrate in a subset of exosomes specifically endocytosed by neurons","volume":"75","author":"Laulagnier","year":"2018","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.bbrc.2017.05.049","article-title":"Fibronectin on extracellular vesicles from microvascular endothelial cells is involved in the vesicle uptake into oligodendrocyte precursor cells","volume":"488","author":"Osawa","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1091\/mbc.e13-04-0212","article-title":"The phosphatidylserine receptor TIM4 utilizes integrins as coreceptors to effect phagocytosis","volume":"25","author":"Flannagan","year":"2014","journal-title":"Mol. Biol. Cell"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.xphs.2016.07.022","article-title":"Role of phosphatidylserine-derived negative surface charges in the recognition and uptake of intravenously injected B16BL6-derived exosomes by macrophages","volume":"106","author":"Matsumoto","year":"2017","journal-title":"J. Pharmalogical Sci."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"1446660","DOI":"10.1080\/20013078.2018.1446660","article-title":"Glycosylated extracellular vesicles released by glioblastoma cells are decorated by CCL18 allowing for cellular uptake via chemokine receptor CCR8","volume":"7","author":"Berenguer","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"1703244","DOI":"10.1080\/20013078.2019.1703244","article-title":"Inhibiting extracellular vesicles formation and release: A review of EV inhibitors","volume":"9","author":"Catalano","year":"2019","journal-title":"J. Extracell. Vesicles"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/8899\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:36:39Z","timestamp":1760178999000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/23\/8899"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,24]]},"references-count":164,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["ijms21238899"],"URL":"https:\/\/doi.org\/10.3390\/ijms21238899","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,24]]}}}