{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:49:15Z","timestamp":1790405355431,"version":"4.1.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:00:00Z","timestamp":1593043200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T00:00:00Z","timestamp":1593043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>There is increasing awareness of the need to consider potential long-term effects of antibiotics on the health of children. In addition to being associated with immune and metabolic diseases, there is evidence that early-life antibiotic exposure can affect neurodevelopment. Here we investigated the effect of low dose of penicillin V on mice when administered for 1 week immediately prior to weaning. We demonstrated that exposure to the antibiotic during the pre-weaning period led to long-term changes in social behaviour, but not anxiety-like traits, in male mice only. The change in behaviour of males was associated with decreased hippocampal expression of AVPR1A and AVPR1B while expression of both receptors was increased in females. Spleens of male mice also showed an increase in the proportion of activated dendritic cells and a corresponding decrease in regulatory T cells with penicillin exposure. All changes in brain, behaviour and immune cell populations, associated with penicillin exposure, were absent in mice that received <jats:italic>L. rhamnosus<\/jats:italic> JB-1 supplementation concurrent with the antibiotic. Our study indicates that post-natal exposure to a clinically relevant dose of antibiotic has long-term, sex dependent effects on the CNS and may have implications for the development of neuropsychiatric disorders. Importantly, we also provide further evidence that probiotic based strategies may be of use in counteracting detrimental effects of early-life antibiotics on neurodevelopment.<\/jats:p>","DOI":"10.1038\/s41598-020-67271-4","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T10:03:02Z","timestamp":1593079382000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Sex dependent effects of post-natal penicillin on brain, behavior and immune regulation are prevented by concurrent probiotic treatment"],"prefix":"10.1038","volume":"10","author":[{"given":"Marya","family":"Kayyal","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanvi","family":"Javkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Firoz Mian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Binyamin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omry","family":"Koren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen-Anne","family":"McVey Neufeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Forsythe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"key":"67271_CR1","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1007\/s00228-009-0679-7","volume":"65","author":"A Clavenna","year":"2009","unstructured":"Clavenna, A. & Bonati, M. Drug prescriptions to outpatient children: a review of the literature. Eur J Clin Pharmacol 65, 749\u2013755 (2009).","journal-title":"Eur J Clin Pharmacol"},{"key":"67271_CR2","doi-asserted-by":"publisher","first-page":"a2245","DOI":"10.1136\/bmj.a2245","volume":"337","author":"MC Sturkenboom","year":"2008","unstructured":"Sturkenboom, M. C. et al. Drug use in children: cohort study in three European countries. BMJ 337, a2245 (2008).","journal-title":"BMJ"},{"key":"67271_CR3","doi-asserted-by":"publisher","first-page":"185","DOI":"10.4161\/viru.22507","volume":"4","author":"IM Gould","year":"2013","unstructured":"Gould, I. M. & Bal, A. M. New antibiotic agents in the pipeline and how they can help overcome microbial resistance. Virulence 4, 185\u2013191 (2013).","journal-title":"Virulence"},{"key":"67271_CR4","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1136\/gut.2010.219683","volume":"60","author":"A Hviid","year":"2011","unstructured":"Hviid, A., Svanstr\u00f6m, H. & Frisch, M. Antibiotic use and inflammatory bowel diseases in childhood. Gut 60, 49\u201354 (2011).","journal-title":"Gut"},{"key":"67271_CR5","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1038\/embor.2012.32","volume":"13","author":"SL Russell","year":"2012","unstructured":"Russell, S. L. et al. Early life antibiotic-driven changes in microbiota enhance susceptibility to allergic asthma. EMBO Rep 13, 440\u2013447 (2012).","journal-title":"EMBO Rep"},{"key":"67271_CR6","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/ijo.2012.132","volume":"37","author":"L Trasande","year":"2013","unstructured":"Trasande, L. et al. Infant antibiotic exposures and early-life body mass. Int J Obes (Lond) 37, 16\u201323 (2013).","journal-title":"Int J Obes (Lond)"},{"key":"67271_CR7","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.phrs.2017.01.034","volume":"119","author":"Y Hu","year":"2017","unstructured":"Hu, Y., Wong, F. S. & Wen, L. Antibiotics, gut microbiota, environment in early life and type 1 diabetes. Pharmacol Res 119, 219\u2013226 (2017).","journal-title":"Pharmacol Res"},{"key":"67271_CR8","doi-asserted-by":"publisher","first-page":"16140","DOI":"10.1038\/nmicrobiol.2016.140","volume":"1","author":"AE Livanos","year":"2016","unstructured":"Livanos, A. E. et al. Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice. Nat Microbiol 1, 16140 (2016).","journal-title":"Nat Microbiol"},{"key":"67271_CR9","doi-asserted-by":"publisher","first-page":"e95476","DOI":"10.1371\/journal.pone.0095476","volume":"9","author":"S Panda","year":"2014","unstructured":"Panda, S. et al. Short-term effect of antibiotics on human gut microbiota. Plos One 9, e95476 (2014).","journal-title":"Plos One"},{"key":"67271_CR10","doi-asserted-by":"publisher","first-page":"343ra81","DOI":"10.1126\/scitranslmed.aad0917","volume":"8","author":"M Yassour","year":"2016","unstructured":"Yassour, M. et al. Natural history of the infant gut microbiome and impact of antibiotic treatment on bacterial strain diversity and stability. Sci Transl Med 8, 343ra81 (2016).","journal-title":"Sci Transl Med"},{"key":"67271_CR11","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1007\/s00018-012-1028-z","volume":"70","author":"P Forsythe","year":"2013","unstructured":"Forsythe, P. & Kunze, W. A. Voices from within: gut microbes and the CNS. Cell Mol Life Sci 70, 55\u201369 (2013).","journal-title":"Cell Mol Life Sci"},{"key":"67271_CR12","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-016-0604-8","volume":"14","author":"P Forsythe","year":"2016","unstructured":"Forsythe, P., Kunze, W. & Bienenstock, J. Moody microbes or fecal phrenology: what do we know about the microbiota-gut-brain axis? BMC Med 14, 58 (2016).","journal-title":"BMC Med"},{"key":"67271_CR13","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1007\/978-1-4939-0897-4_17","volume":"817","author":"YE Borre","year":"2014","unstructured":"Borre, Y. E., Moloney, R. D., Clarke, G., Dinan, T. G. & Cryan, J. F. The impact of microbiota on brain and behavior: mechanisms & therapeutic potential. Adv Exp Med Biol 817, 373\u2013403 (2014).","journal-title":"Adv Exp Med Biol"},{"issue":"255\u201364","key":"67271_CR14","first-page":"e119","volume":"23","author":"KM Neufeld","year":"2011","unstructured":"Neufeld, K. M., Kang, N., Bienenstock, J. & Foster, J. A. Reduced anxiety-like behavior and central neurochemical change in germ-free mice. Neurogastroenterol Motil 23(255\u201364), e119 (2011).","journal-title":"Neurogastroenterol Motil"},{"key":"67271_CR15","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.bbi.2013.12.005","volume":"37","author":"CG de Theije","year":"2014","unstructured":"de Theije, C. G. et al. Altered gut microbiota and activity in a murine model of autism spectrum disorders. Brain Behav Immun 37, 197\u2013206 (2014).","journal-title":"Brain Behav Immun"},{"issue":"599\u2013609","key":"67271_CR16","first-page":"609.e1","volume":"141","author":"P Bercik","year":"2011","unstructured":"Bercik, P. et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141(599\u2013609), 609.e1 (2011).","journal-title":"Gastroenterology"},{"key":"67271_CR17","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.bbi.2015.04.004","volume":"48","author":"L Desbonnet","year":"2015","unstructured":"Desbonnet, L. et al. Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour. Brain Behav Immun 48, 165\u2013173 (2015).","journal-title":"Brain Behav Immun"},{"key":"67271_CR18","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15062","volume":"8","author":"S Leclercq","year":"2017","unstructured":"Leclercq, S. et al. Low-dose penicillin in early life induces long-term changes in murine gut microbiota, brain cytokines and behavior. Nat Commun 8, 15062 (2017).","journal-title":"Nat Commun"},{"key":"67271_CR19","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1055\/s-2007-973720","volume":"28","author":"N Herschkowitz","year":"1997","unstructured":"Herschkowitz, N., Kagan, J. & Zilles, K. Neurobiological bases of behavioral development in the first year. Neuropediatrics 28, 296\u2013306 (1997).","journal-title":"Neuropediatrics"},{"key":"67271_CR20","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1038\/nn1971","volume":"10","author":"K Martinowich","year":"2007","unstructured":"Martinowich, K., Manji, H. & Lu, B. New insights into BDNF function in depression and anxiety. Nat Neurosci 10, 1089\u20131093 (2007).","journal-title":"Nat Neurosci"},{"key":"67271_CR21","doi-asserted-by":"crossref","unstructured":"Luczynski, P.et al. Growing up in a Bubble: Using Germ-Free Animals to Assess the Influence of the Gut Microbiota on Brain and Behavior. Int J Neuropsychopharmacol 19 (2016).","DOI":"10.1093\/ijnp\/pyw020"},{"key":"67271_CR22","doi-asserted-by":"publisher","first-page":"146352","DOI":"10.1016\/j.brainres.2019.146352","volume":"1722","author":"RV Pearse","year":"2019","unstructured":"Pearse, R. V. & Young-Pearse, T. L. Lost in translational biology: Understanding sex differences to inform studies of diseases of the nervous system. Brain Res 1722, 146352 (2019).","journal-title":"Brain Res"},{"key":"67271_CR23","doi-asserted-by":"publisher","unstructured":"Bharwani, A., Mian, M. F., Surette, M. G., Bienenstock, J. & Forsythe, P. Oral treatment with Lactobacillus rhamnosus attenuates behavioural deficits and immune changes in chronic social stress. BMC Med 15, https:\/\/doi.org\/10.1186\/s12916-016 (2017).","DOI":"10.1186\/s12916-016"},{"key":"67271_CR24","doi-asserted-by":"publisher","first-page":"16050","DOI":"10.1073\/pnas.1102999108","volume":"108","author":"JA Bravo","year":"2011","unstructured":"Bravo, J. A. et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proc Natl Acad Sci U S A 108, 16050\u201316055 (2011).","journal-title":"Proc Natl Acad Sci U S A"},{"key":"67271_CR25","first-page":"600","volume":"50","author":"PV Turner","year":"2011","unstructured":"Turner, P. V., Brabb, T., Pekow, C. & Vasbinder, M. A. Administration of substances to laboratory animals: routes of administration and factors to consider. J Am Assoc Lab Anim Sci 50, 600\u2013613 (2011).","journal-title":"J Am Assoc Lab Anim Sci"},{"key":"67271_CR26","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.psyneuen.2015.10.001","volume":"63","author":"A Bharwani","year":"2015","unstructured":"Bharwani, A. et al. Structural & functional consequences of chronic psychosocial stress on the microbiome & host. Psychoneuroendocrinology 63, 217\u2013227 (2015).","journal-title":"Psychoneuroendocrinology"},{"key":"67271_CR27","doi-asserted-by":"publisher","DOI":"10.1186\/s40364-017-0112-9","volume":"5","author":"SY Lim","year":"2017","unstructured":"Lim, S. Y. et al. Evaluation of two high-throughput proteomic technologies for plasma biomarker discovery in immunotherapy-treated melanoma patients. Biomark Res 5, 32 (2017).","journal-title":"Biomark Res"},{"key":"67271_CR28","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1038\/s41587-019-0209-9","volume":"37","author":"E Bolyen","year":"2019","unstructured":"Bolyen, E. et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol 37, 852\u2013857 (2019).","journal-title":"Nat Biotechnol"},{"key":"67271_CR29","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/nmeth.3869","volume":"13","author":"BJ Callahan","year":"2016","unstructured":"Callahan, B. J. et al. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods 13, 581\u2013583 (2016).","journal-title":"Nat Methods"},{"key":"67271_CR30","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1098\/rstb.1994.0085","volume":"345","author":"DP Faith","year":"1994","unstructured":"Faith, D. P. Phylogenetic pattern and the quantification of organismal biodiversity. Philos Trans R Soc Lond B Biol Sci 345, 45\u201358 (1994).","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"key":"67271_CR31","first-page":"121","volume":"2","author":"DP Faith","year":"2007","unstructured":"Faith, D. P. & Baker, A. M. Phylogenetic diversity (PD) and biodiversity conservation: some bioinformatics challenges. Evol Bioinform Online 2, 121\u2013128 (2007).","journal-title":"Evol Bioinform Online"},{"key":"67271_CR32","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-015-0640-y","volume":"16","author":"CA Lozupone","year":"2015","unstructured":"Lozupone, C. A. & Knight, R. The UniFrac significance test is sensitive to tree topology. BMC Bioinformatics 16, 211 (2015).","journal-title":"BMC Bioinformatics"},{"key":"67271_CR33","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1096\/fj.201600781r","volume":"31","author":"LR Miller","year":"2017","unstructured":"Miller, L. R. et al. Considering sex as a biological variable in preclinical research. FASEB J 31, 29\u201334 (2017).","journal-title":"FASEB J"},{"key":"67271_CR34","doi-asserted-by":"publisher","first-page":"263ra158","DOI":"10.1126\/scitranslmed.3009759","volume":"6","author":"V Braniste","year":"2014","unstructured":"Braniste, V. et al. The gut microbiota influences blood-brain barrier permeability in mice. Sci Transl Med 6, 263ra158 (2014).","journal-title":"Sci Transl Med"},{"key":"67271_CR35","doi-asserted-by":"publisher","first-page":"E3130","DOI":"10.1073\/pnas.1600324113","volume":"113","author":"SO Reber","year":"2016","unstructured":"Reber, S. O. et al. Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice. Proc Natl Acad Sci U S A 113, E3130\u20139 (2016).","journal-title":"Proc Natl Acad Sci U S A"},{"key":"67271_CR36","doi-asserted-by":"publisher","first-page":"e42054","DOI":"10.1371\/journal.pone.0042054","volume":"7","author":"SJ Kim","year":"2012","unstructured":"Kim, S. J. et al. CD4\u2009+\u2009CD25+ regulatory T cell depletion modulates anxiety and depression-like behaviors in mice. PLoS One 7, e42054 (2012).","journal-title":"PLoS One"},{"key":"67271_CR37","doi-asserted-by":"publisher","first-page":"479","DOI":"10.7326\/0003-4819-134-6-200103200-00013","volume":"134","author":"R Gonzales","year":"2001","unstructured":"Gonzales, R. et al. Principles of appropriate antibiotic use for treatment of acute respiratory tract infections in adults: background, specific aims, and methods. Ann Intern Med 134, 479\u2013486 (2001).","journal-title":"Ann Intern Med"},{"key":"67271_CR38","doi-asserted-by":"publisher","first-page":"303","DOI":"10.5001\/omj.2011.77","volume":"26","author":"N Kutty","year":"2011","unstructured":"Kutty, N. Treating children without antibiotics in primary healthcare. Oman Med J 26, 303\u2013305 (2011).","journal-title":"Oman Med J"},{"key":"67271_CR39","first-page":"489","volume":"42","author":"H Neuman","year":"2018","unstructured":"Neuman, H., Forsythe, P., Uzan, A., Avni, O. & Koren, O. Antibiotics in early life: dysbiosis and the damage done. FEMS Microbiol Rev 42, 489\u2013499 (2018).","journal-title":"FEMS Microbiol Rev"},{"key":"67271_CR40","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1111\/apa.13613","volume":"106","author":"RF Slykerman","year":"2017","unstructured":"Slykerman, R. F. et al. Antibiotics in the first year of life and subsequent neurocognitive outcomes. Acta Paediatr 106, 87\u201394 (2017).","journal-title":"Acta Paediatr"},{"key":"67271_CR41","doi-asserted-by":"crossref","unstructured":"Champagne-Jorgensen, K.et al. Prenatal low-dose penicillin results in long-term sex-specific changes to murine behaviour, immune regulation, and gut microbiota. Brain Behav Immun (2019).","DOI":"10.1016\/j.bbi.2019.11.020"},{"key":"67271_CR42","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/S0079-6123(08)00406-8","volume":"170","author":"HK Caldwell","year":"2008","unstructured":"Caldwell, H. K., Wersinger, S. R. & Young, W. S. The role of the vasopressin 1b receptor in aggression and other social behaviours. Prog Brain Res 170, 65\u201372 (2008).","journal-title":"Prog Brain Res"},{"key":"67271_CR43","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.yhbeh.2011.11.009","volume":"61","author":"EL Stevenson","year":"2012","unstructured":"Stevenson, E. L. & Caldwell, H. K. The vasopressin 1b receptor and the neural regulation of social behavior. Horm Behav 61, 277\u2013282 (2012).","journal-title":"Horm Behav"},{"key":"67271_CR44","first-page":"1013","volume":"7","author":"R Charles","year":"2014","unstructured":"Charles, R. et al. Introduction of the human AVPR1A gene substantially alters brain receptor expression patterns and enhances aspects of social behavior in transgenic mice. Dis Model Mech 7, 1013\u20131022 (2014).","journal-title":"Dis Model Mech"},{"key":"67271_CR45","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S0065-2660(07)59004-8","volume":"59","author":"EA Hammock","year":"2007","unstructured":"Hammock, E. A. Gene regulation as a modulator of social preference in voles. Adv Genet 59, 107\u2013127 (2007).","journal-title":"Adv Genet"},{"key":"67271_CR46","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.yhbeh.2004.07.004","volume":"46","author":"SR Wersinger","year":"2004","unstructured":"Wersinger, S. R. et al. Social motivation is reduced in vasopressin 1b receptor null mice despite normal performance in an olfactory discrimination task. Horm Behav 46, 638\u2013645 (2004).","journal-title":"Horm Behav"},{"key":"67271_CR47","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.bbr.2005.06.005","volume":"164","author":"IF Bielsky","year":"2005","unstructured":"Bielsky, I. F., Hu, S. B. & Young, L. J. Sexual dimorphism in the vasopressin system: lack of an altered behavioral phenotype in female V1a receptor knockout mice. Behav Brain Res 164, 132\u2013136 (2005).","journal-title":"Behav Brain Res"},{"key":"67271_CR48","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.neuropharm.2016.07.018","volume":"110","author":"N Duque-Wilckens","year":"2016","unstructured":"Duque-Wilckens, N. et al. Inhibition of vasopressin V1a receptors in the medioventral bed nucleus of the stria terminalis has sex- and context-specific anxiogenic effects. Neuropharmacology 110, 59\u201368 (2016).","journal-title":"Neuropharmacology"},{"key":"67271_CR49","doi-asserted-by":"publisher","first-page":"216","DOI":"10.3389\/fnbeh.2014.00216","volume":"8","author":"R Bredewold","year":"2014","unstructured":"Bredewold, R., Smith, C. J., Dumais, K. M. & Veenema, A. H. Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context. Front Behav Neurosci 8, 216 (2014).","journal-title":"Front Behav Neurosci"},{"key":"67271_CR50","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-016-0310-7","volume":"17","author":"SK Witchey","year":"2016","unstructured":"Witchey, S. K., Stevenson, E. L. & Caldwell, H. K. Genotypic differences in intruder-evoked immediate early gene activation in male, but not female, vasopressin 1b receptor knockout mice. BMC Neurosci 17, 75 (2016).","journal-title":"BMC Neurosci"},{"key":"67271_CR51","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-017-0169-1","volume":"8","author":"S Netser","year":"2017","unstructured":"Netser, S., Haskal, S., Magalnik, H. & Wagner, S. A novel system for tracking social preference dynamics in mice reveals sex- and strain-specific characteristics. Mol Autism 8, 53 (2017).","journal-title":"Mol Autism"},{"key":"67271_CR52","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1038\/s41593-017-0010-3","volume":"20","author":"C Menard","year":"2017","unstructured":"Menard, C. et al. Social stress induces neurovascular pathology promoting depression. Nat Neurosci 20, 1752\u20131760 (2017).","journal-title":"Nat Neurosci"},{"key":"67271_CR53","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/S1537-1891(02)00200-8","volume":"38","author":"H Wolburg","year":"2002","unstructured":"Wolburg, H. & Lippoldt, A. Tight junctions of the blood-brain barrier: development, composition and regulation. Vascul Pharmacol 38, 323\u2013337 (2002).","journal-title":"Vascul Pharmacol"},{"key":"67271_CR54","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/S0166-2236(00)02004-X","volume":"24","author":"JD Huber","year":"2001","unstructured":"Huber, J. D., Egleton, R. D. & Davis, T. P. Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier. Trends Neurosci 24, 719\u2013725 (2001).","journal-title":"Trends Neurosci"},{"key":"67271_CR55","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/978-1-4939-0897-4_15","volume":"817","author":"GA Rook","year":"2014","unstructured":"Rook, G. A., Raison, C. L. & Lowry, C. A. Microbiota, immunoregulatory old friends and psychiatric disorders. Adv Exp Med Biol 817, 319\u2013356 (2014).","journal-title":"Adv Exp Med Biol"},{"key":"67271_CR56","unstructured":"Liu, Y., Firoz Mian, M., McVey Neufeld, K. A. & Forsythe, P. CD4. Brain Behav Immun (2020)."},{"key":"67271_CR57","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1038\/mp.2012.77","volume":"18","author":"G Clarke","year":"2013","unstructured":"Clarke, G. et al. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry 18, 666\u2013673 (2013).","journal-title":"Mol Psychiatry"},{"key":"67271_CR58","unstructured":"Grayson, M. L., Crowe, S. M., McCarthy, J. S. & Mills, J. Kucers\u2019 The Use of Antibiotics Sixth Edition: A Clinical Review of Antibacterial, Antifungal and Antiviral Drugs 2010)."},{"key":"67271_CR59","doi-asserted-by":"publisher","first-page":"588","DOI":"10.3389\/fnins.2017.00588","volume":"11","author":"T Delungahawatta","year":"2017","unstructured":"Delungahawatta, T. et al. Antibiotic Driven Changes in Gut Motility Suggest Direct Modulation of Enteric Nervous System. Front Neurosci 11, 588 (2017).","journal-title":"Front Neurosci"},{"key":"67271_CR60","doi-asserted-by":"publisher","first-page":"3064","DOI":"10.1096\/fj.13-245282","volume":"28","author":"A Perez-Burgos","year":"2014","unstructured":"Perez-Burgos, A., Mao, Y. K., Bienenstock, J. & Kunze, W. A. The gut-brain axis rewired: adding a functional vagal nicotinic \u201csensory synapse\u201d. FASEB J 28, 3064\u20133074 (2014).","journal-title":"FASEB J"},{"key":"67271_CR61","doi-asserted-by":"publisher","first-page":"294","DOI":"10.3389\/fnins.2018.00294","volume":"12","author":"KA McVey Neufeld","year":"2018","unstructured":"McVey Neufeld, K. A., Kay, S. & Bienenstock, J. Mouse Strain Affects Behavioral and Neuroendocrine Stress Responses Following Administration of Probiotic. Front Neurosci 12, 294 (2018).","journal-title":"Front Neurosci"},{"key":"67271_CR62","doi-asserted-by":"publisher","first-page":"e47556","DOI":"10.1371\/journal.pone.0047556","volume":"7","author":"K Karimi","year":"2012","unstructured":"Karimi, K., Kandiah, N., Chau, J., Bienenstock, J. & Forsythe, P. A Lactobacillus rhamnosus Strain Induces a Heme Oxygenase Dependent Increase in Foxp3+ Regulatory T Cells. Plos One 7, e47556 (2012).","journal-title":"Plos One"},{"key":"67271_CR63","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1164\/rccm.200806-951OC","volume":"179","author":"K Karimi","year":"2009","unstructured":"Karimi, K., Inman, M. D., Bienenstock, J. & Forsythe, P. Lactobacillus reuteri-induced regulatory T cells protect against an allergic airway response in mice. Am J Respir Crit Care Med 179, 186\u2013193 (2009).","journal-title":"Am J Respir Crit Care Med"}],"updated-by":[{"DOI":"10.1038\/s41598-020-75606-4","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000}}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67271-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67271-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67271-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T12:35:03Z","timestamp":1670330103000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-67271-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,25]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["67271"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-67271-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,25]]},"assertion":[{"value":"21 January 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 May 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 October 2020","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"An amendment to this paper has been published and can be accessed via a link at the top of the paper.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"10318"}}