{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:05:31Z","timestamp":1787317531288,"version":"build-2736575974"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,21]],"date-time":"2024-05-21T00:00:00Z","timestamp":1716249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"crossref","award":["JP21K15351"],"award-info":[{"award-number":["JP21K15351"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Ulcerative colitis (UC) is a refractory inflammatory bowel disease, which is known to cause psychiatric disorders such as anxiety and depression at a high rate in addition to peripheral inflammatory symptoms. However, the pathogenesis of these psychiatric disorders remains mostly unknown. While prior research revealed that the\n                    <jats:italic>Enterococcus faecalis<\/jats:italic>\n                    2001 (EF-2001) suppressed UC-like symptoms and accompanying depressive-like behaviors, observed in a UC model using dextran sulfate sodium (DSS), whether it has an anxiolytic effect remains unclear. Therefore, we examined whether EF-2001 attenuates DSS-induced anxiety-like behaviors. Treatment with 2% DSS for seven days induced UC-like symptoms and anxiety-like behavior through the hole-board test, increased serum lipopolysaccharide (LPS) and corticosterone concentration, and\n                    <jats:italic>p<\/jats:italic>\n                    -glucocorticoid receptor (GR) in the prefrontal cortex (PFC), and decreased\n                    <jats:italic>N<\/jats:italic>\n                    -methyl-\n                    <jats:sc>d<\/jats:sc>\n                    -aspartate receptor subunit (NR) 2A and NR2B expression levels in the PFC. Interestingly, these changes were reversed by EF-2001 administration. Further, EF-2001 administration enhanced CAMKII\/CREB\/BDNF-Drebrin pathways in the PFC of DSS-treated mice, and labeling of p-GR, p-CAMKII, and p-CREB showed colocalization with neurons. EF-2001 attenuated anxiety-like behavior by reducing serum LPS and corticosterone levels linked to the improvement of UC symptoms and by facilitating the CAMKII\/CREB\/BDNF-Drebrin pathways in the PFC. Our findings suggest a close relationship between UC and anxiety.\n                  <\/jats:p>","DOI":"10.1038\/s41598-024-62309-3","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T22:01:44Z","timestamp":1716242504000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Anxiolytic effects of Enterococcus faecalis 2001 on a mouse model of colitis"],"prefix":"10.1038","volume":"14","author":[{"given":"Kohei","family":"Takahashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Tsuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Nakagawasai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Miyagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Kurokawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsumi","family":"Mochida-Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Iwasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Iwasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Takeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Tadano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,21]]},"reference":[{"key":"62309_CR1","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1002\/ibd.20873","volume":"15","author":"LA Graff","year":"2009","unstructured":"Graff, L. A., Walker, J. R. & Bernstein, C. N. Depression and anxiety in inflammatory bowel disease: A review of comorbidity and management. Inflamm. Bowel Dis. 15, 1105\u20131118. https:\/\/doi.org\/10.1002\/ibd.20873 (2009).","journal-title":"Inflamm. Bowel Dis."},{"key":"62309_CR2","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1136\/jech.55.10.716","volume":"55","author":"LM Kurina","year":"2001","unstructured":"Kurina, L. M., Goldacre, M. J., Yeates, D. & Gill, L. E. Depression and anxiety in people with inflammatory bowel disease. J. Epidemiol. Community Health 55, 716\u2013720. https:\/\/doi.org\/10.1136\/jech.55.10.716 (2001).","journal-title":"J. Epidemiol. Community Health"},{"issue":"Suppl 8","key":"62309_CR3","first-page":"38","volume":"62","author":"RB Lydiard","year":"2001","unstructured":"Lydiard, R. B. Irritable bowel syndrome, anxiety, and depression: What are the links?. J. Clin. Psychiatry 62(Suppl 8), 38\u201345 (2001) (discussion 46\u201337).","journal-title":"J. Clin. Psychiatry"},{"key":"62309_CR4","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1186\/1745-0179-2-24","volume":"2","author":"AA Mikocka-Walus","year":"2006","unstructured":"Mikocka-Walus, A. A. et al. Antidepressants and inflammatory bowel disease: A systematic review. Clin. Pract. Epidemiol. Ment. Health 2, 24. https:\/\/doi.org\/10.1186\/1745-0179-2-24 (2006).","journal-title":"Clin. Pract. Epidemiol. Ment. Health"},{"key":"62309_CR5","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1007\/s40473-017-0129-2","volume":"4","author":"P Perez-Pardo","year":"2017","unstructured":"Perez-Pardo, P., Hartog, M., Garssen, J. & Kraneveld, A. D. Microbes tickling your tummy: The importance of the gut\u2013brain axis in Parkinson\u2019s disease. Curr. Behav. Neurosci. Rep. 4, 361\u2013368. https:\/\/doi.org\/10.1007\/s40473-017-0129-2 (2017).","journal-title":"Curr. Behav. Neurosci. Rep."},{"key":"62309_CR6","doi-asserted-by":"publisher","first-page":"4053","DOI":"10.3748\/wjg.v28.i30.4053","volume":"28","author":"AEV Quaglio","year":"2022","unstructured":"Quaglio, A. E. V., Grillo, T. G., De Oliveira, E. C. S., Di Stasi, L. C. & Sassaki, L. Y. Gut microbiota, inflammatory bowel disease and colorectal cancer. World J. Gastroenterol. 28, 4053\u20134060. https:\/\/doi.org\/10.3748\/wjg.v28.i30.4053 (2022).","journal-title":"World J. Gastroenterol."},{"key":"62309_CR7","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1007\/s12325-020-01272-7","volume":"37","author":"A Capuco","year":"2020","unstructured":"Capuco, A. et al. Current perspectives on gut microbiome dysbiosis and depression. Adv. Ther. 37, 1328\u20131346. https:\/\/doi.org\/10.1007\/s12325-020-01272-7 (2020).","journal-title":"Adv. Ther."},{"key":"62309_CR8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108834","volume":"201","author":"W Li","year":"2021","unstructured":"Li, W. et al. TRPV4 inhibitor HC067047 produces antidepressant-like effect in LPS-induced depression mouse model. Neuropharmacology 201, 108834. https:\/\/doi.org\/10.1016\/j.neuropharm.2021.108834 (2021).","journal-title":"Neuropharmacology"},{"key":"62309_CR9","doi-asserted-by":"publisher","first-page":"7975","DOI":"10.1523\/JNEUROSCI.6078-09.2010","volume":"30","author":"A Mouihate","year":"2010","unstructured":"Mouihate, A. et al. Early life activation of toll-like receptor 4 reprograms neural anti-inflammatory pathways. J. Neurosci. 30, 7975\u20137983. https:\/\/doi.org\/10.1523\/JNEUROSCI.6078-09.2010 (2010).","journal-title":"J. Neurosci."},{"key":"62309_CR10","doi-asserted-by":"publisher","DOI":"10.14814\/phy2.13639","author":"KE Sylvia","year":"2018","unstructured":"Sylvia, K. E. & Demas, G. E. Acute intraperitoneal lipopolysaccharide influences the immune system in the absence of gut dysbiosis. Physiol. Rep. https:\/\/doi.org\/10.14814\/phy2.13639 (2018).","journal-title":"Physiol. Rep."},{"key":"62309_CR11","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/j.neuroscience.2015.06.035","volume":"305","author":"O Girard-Joyal","year":"2015","unstructured":"Girard-Joyal, O. et al. Age and sex differences in c-Fos expression and serum corticosterone concentration following LPS treatment. Neuroscience 305, 293\u2013301. https:\/\/doi.org\/10.1016\/j.neuroscience.2015.06.035 (2015).","journal-title":"Neuroscience"},{"key":"62309_CR12","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2022.148189","volume":"1800","author":"JL Scholl","year":"2023","unstructured":"Scholl, J. L., Solanki, R. R., Watt, M. J., Renner, K. J. & Forster, G. L. Chronic administration of glucocorticoid receptor ligands increases anxiety-like behavior and selectively increase serotonin transporters in the ventral hippocampus. Brain Res. 1800, 148189. https:\/\/doi.org\/10.1016\/j.brainres.2022.148189 (2023).","journal-title":"Brain Res."},{"key":"62309_CR13","doi-asserted-by":"publisher","first-page":"11851","DOI":"10.1073\/pnas.0402208101","volume":"101","author":"Q Wei","year":"2004","unstructured":"Wei, Q. et al. Glucocorticoid receptor overexpression in forebrain: A mouse model of increased emotional lability. Proc. Natl. Acad. Sci. U. S. A. 101, 11851\u201311856. https:\/\/doi.org\/10.1073\/pnas.0402208101 (2004).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"62309_CR14","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232012328","author":"M Piechota","year":"2022","unstructured":"Piechota, M. et al. Glucocorticoid-regulated kinase CAMKI\u03b3 in the central amygdala controls anxiety-like behavior in mice. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms232012328 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"62309_CR15","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1016\/j.yhbeh.2014.09.010","volume":"66","author":"DC Wang","year":"2014","unstructured":"Wang, D. C., Chen, T. J., Lin, M. L., Jhong, Y. C. & Chen, S. C. Exercise prevents the increased anxiety-like behavior in lactational di-(2-ethylhexyl) phthalate-exposed female rats in late adolescence by improving the regulation of hypothalamus\u2013pituitary\u2013adrenal axis. Horm. Behav. 66, 674\u2013684. https:\/\/doi.org\/10.1016\/j.yhbeh.2014.09.010 (2014).","journal-title":"Horm. Behav."},{"key":"62309_CR16","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/j.bbi.2021.07.022","volume":"97","author":"K Picard","year":"2021","unstructured":"Picard, K. et al. Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. Brain Behav. Immun. 97, 423\u2013439. https:\/\/doi.org\/10.1016\/j.bbi.2021.07.022 (2021).","journal-title":"Brain Behav. Immun."},{"key":"62309_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2019.100161","volume":"10","author":"G Dominguez","year":"2019","unstructured":"Dominguez, G. et al. Sustained corticosterone rise in the prefrontal cortex is a key factor for chronic stress-induced working memory deficits in mice. Neurobiol. Stress 10, 100161. https:\/\/doi.org\/10.1016\/j.ynstr.2019.100161 (2019).","journal-title":"Neurobiol. Stress"},{"key":"62309_CR18","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1038\/npp.2008.123","volume":"34","author":"SL Gourley","year":"2009","unstructured":"Gourley, S. L., Kedves, A. T., Olausson, P. & Taylor, J. R. A history of corticosterone exposure regulates fear extinction and cortical NR2B, GluR2\/3, and BDNF. Neuropsychopharmacology 34, 707\u2013716. https:\/\/doi.org\/10.1038\/npp.2008.123 (2009).","journal-title":"Neuropsychopharmacology"},{"key":"62309_CR19","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1007\/s12640-020-00201-4","volume":"38","author":"Y Liu","year":"2020","unstructured":"Liu, Y. et al. Corticosterone induced the increase of proBDNF in primary hippocampal neurons via endoplasmic reticulum stress. Neurotox. Res. 38, 370\u2013384. https:\/\/doi.org\/10.1007\/s12640-020-00201-4 (2020).","journal-title":"Neurotox. Res."},{"key":"62309_CR20","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1016\/j.neuroscience.2019.07.018","volume":"415","author":"W Ren","year":"2019","unstructured":"Ren, W. et al. Embryonic ketamine produces a downregulation of prefrontal cortex NMDA receptors and anxiety-like behavior in adult offspring. Neuroscience 415, 18\u201330. https:\/\/doi.org\/10.1016\/j.neuroscience.2019.07.018 (2019).","journal-title":"Neuroscience"},{"key":"62309_CR21","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.neulet.2011.10.039","volume":"505","author":"N Uysal","year":"2011","unstructured":"Uysal, N. et al. Maternal exercise decreases maternal deprivation induced anxiety of pups and correlates to increased prefrontal cortex BDNF and VEGF. Neurosci. Lett. 505, 273\u2013278. https:\/\/doi.org\/10.1016\/j.neulet.2011.10.039 (2011).","journal-title":"Neurosci. Lett."},{"key":"62309_CR22","doi-asserted-by":"publisher","DOI":"10.1016\/j.ynstr.2022.100503","volume":"21","author":"Y Li","year":"2022","unstructured":"Li, Y. et al. (2R,6R)-hydroxynorketamine acts through GluA1-induced synaptic plasticity to alleviate PTSD-like effects in rat models. Neurobiol. Stress. 21, 100503. https:\/\/doi.org\/10.1016\/j.ynstr.2022.100503 (2022).","journal-title":"Neurobiol. Stress."},{"key":"62309_CR23","doi-asserted-by":"publisher","first-page":"3889","DOI":"10.1007\/s12035-017-0596-1","volume":"55","author":"S Moriguchi","year":"2018","unstructured":"Moriguchi, S. et al. Reduced CaM kinase II and CaM kinase IV activities underlie cognitive deficits in NCKX2 heterozygous mice. Mol. Neurobiol. 55, 3889\u20133900. https:\/\/doi.org\/10.1007\/s12035-017-0596-1 (2018).","journal-title":"Mol. Neurobiol."},{"key":"62309_CR24","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.jphs.2019.07.015","volume":"140","author":"Y Yabuki","year":"2019","unstructured":"Yabuki, Y., Wu, L. & Fukunaga, K. Cognitive enhancer ST101 improves schizophrenia-like behaviors in neonatal ventral hippocampus-lesioned rats in association with improved CaMKII\/PKC pathway. J. Pharmacol. Sci. 140, 263\u2013272. https:\/\/doi.org\/10.1016\/j.jphs.2019.07.015 (2019).","journal-title":"J. Pharmacol. Sci."},{"key":"62309_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2019.110671","volume":"503","author":"G Guo","year":"2020","unstructured":"Guo, G. et al. Testosterone modulates structural synaptic plasticity of primary cultured hippocampal neurons through ERK\u2013CREB signalling pathways. Mol. Cell Endocrinol. 503, 110671. https:\/\/doi.org\/10.1016\/j.mce.2019.110671 (2020).","journal-title":"Mol. Cell Endocrinol."},{"key":"62309_CR26","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1101\/lm.029520.112","volume":"20","author":"D Baker-Andresen","year":"2013","unstructured":"Baker-Andresen, D., Flavell, C. R., Li, X. & Bredy, T. W. Activation of BDNF signaling prevents the return of fear in female mice. Learn. Mem. 20, 237\u2013240. https:\/\/doi.org\/10.1101\/lm.029520.112 (2013).","journal-title":"Learn. Mem."},{"key":"62309_CR27","doi-asserted-by":"publisher","DOI":"10.1002\/syn.22253","volume":"77","author":"R Temizer","year":"2023","unstructured":"Temizer, R., Chen, Y. W. & Aoki, C. Individual differences in the positive outcome from adolescent ketamine treatment in a female mouse model of anorexia nervosa involve drebrin A at excitatory synapses of the medial prefrontal cortex. Synapse 77, e22253. https:\/\/doi.org\/10.1002\/syn.22253 (2023).","journal-title":"Synapse"},{"key":"62309_CR28","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s12974-022-02431-z","volume":"19","author":"NL Cluny","year":"2022","unstructured":"Cluny, N. L. et al. Recruitment of alpha4beta7 monocytes and neutrophils to the brain in experimental colitis is associated with elevated cytokines and anxiety-like behavior. J. Neuroinflamm. 19, 73. https:\/\/doi.org\/10.1186\/s12974-022-02431-z (2022).","journal-title":"J. Neuroinflamm."},{"key":"62309_CR29","doi-asserted-by":"publisher","first-page":"3963","DOI":"10.1021\/acs.jafc.0c00196","volume":"68","author":"B Zhao","year":"2020","unstructured":"Zhao, B. et al. Lycopene alleviates DSS-induced colitis and behavioral disorders via mediating microbes\u2013gut\u2013brain axis balance. J. Agric. Food Chem. 68, 3963\u20133975. https:\/\/doi.org\/10.1021\/acs.jafc.0c00196 (2020).","journal-title":"J. Agric. Food Chem."},{"key":"62309_CR30","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2020.112640","volume":"390","author":"O Nakagawasai","year":"2020","unstructured":"Nakagawasai, O. et al. Liver hydrolysate prevents depressive-like behavior in an animal model of colitis: Involvement of hippocampal neurogenesis via the AMPK\/BDNF pathway. Behav. Brain Res. 390, 112640. https:\/\/doi.org\/10.1016\/j.bbr.2020.112640 (2020).","journal-title":"Behav. Brain Res."},{"key":"62309_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2023.114671","volume":"373","author":"K Takahashi","year":"2023","unstructured":"Takahashi, K. et al. Hippocampal and gut AMPK activation attenuates enterocolitis-like symptoms and co-occurring depressive-like behavior in ulcerative colitis model mice: Involvement of brain-gut autophagy. Exp. Neurol. 373, 114671. https:\/\/doi.org\/10.1016\/j.expneurol.2023.114671 (2023).","journal-title":"Exp. Neurol."},{"key":"62309_CR32","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1186\/s12974-019-1580-7","volume":"16","author":"K Takahashi","year":"2019","unstructured":"Takahashi, K. et al. Effect of Enterococcus faecalis 2001 on colitis and depressive-like behavior in dextran sulfate sodium-treated mice: involvement of the brain\u2013gut axis. J. Neuroinflamm. 16, 201. https:\/\/doi.org\/10.1186\/s12974-019-1580-7 (2019).","journal-title":"J. Neuroinflamm."},{"key":"62309_CR33","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.14306","volume":"46","author":"HV Sudeep","year":"2022","unstructured":"Sudeep, H. V., Venkatakrishna, K., Raj, A., Reethi, B. & Shyamprasad, K. Viphyllin\u2122, a standardized extract from black pepper seeds, mitigates intestinal inflammation, oxidative stress, and anxiety-like behavior in DSS-induced colitis mice. J. Food Biochem. 46, e14306. https:\/\/doi.org\/10.1111\/jfbc.14306 (2022).","journal-title":"J. Food Biochem."},{"key":"62309_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101535","volume":"32","author":"X Zhang","year":"2020","unstructured":"Zhang, X. et al. Effects of alternate-day fasting, time-restricted fasting and intermittent energy restriction DSS-induced on colitis and behavioral disorders. Redox Biol. 32, 101535. https:\/\/doi.org\/10.1016\/j.redox.2020.101535 (2020).","journal-title":"Redox Biol."},{"key":"62309_CR35","first-page":"91","volume":"30","author":"R Sagarwala","year":"2018","unstructured":"Sagarwala, R., Malmstrom, T. & Nasrallah, H. A. Effects of nonpharmacological therapies on anxiety and cortisol: A meta-analysis. Ann. Clin. Psychiatry 30, 91\u201396 (2018).","journal-title":"Ann. Clin. Psychiatry"},{"key":"62309_CR36","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1007\/s10068-016-0175-7","volume":"25","author":"EJ Choi","year":"2016","unstructured":"Choi, E. J. et al. Effect of Enterococcus faecalis EF-2001 on experimentally induced atopic eczema in mice. Food Sci. Biotechnol. 25, 1087\u20131093. https:\/\/doi.org\/10.1007\/s10068-016-0175-7 (2016).","journal-title":"Food Sci. Biotechnol."},{"key":"62309_CR37","doi-asserted-by":"publisher","first-page":"146","DOI":"10.3390\/nu8030146","volume":"8","author":"EJ Choi","year":"2016","unstructured":"Choi, E. J. et al. Heat-killed Enterococcus faecalis EF-2001 ameliorates atopic dermatitis in a murine model. Nutrients 8, 146. https:\/\/doi.org\/10.3390\/nu8030146 (2016).","journal-title":"Nutrients"},{"key":"62309_CR38","doi-asserted-by":"publisher","first-page":"653","DOI":"10.2174\/1389201018666171002130428","volume":"18","author":"YH Gu","year":"2017","unstructured":"Gu, Y. H. et al. Pharmaceutical production of anti-tumor and immune-potentiating Enterococcus faecalis-2001 \u03b2-glucans: Enhanced activity of macrophage and lymphocytes in tumor-implanted mice. Curr. Pharm. Biotechnol. 18, 653\u2013661. https:\/\/doi.org\/10.2174\/1389201018666171002130428 (2017).","journal-title":"Curr. Pharm. Biotechnol."},{"key":"62309_CR39","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.959063","volume":"13","author":"H Hamamoto","year":"2022","unstructured":"Hamamoto, H., Ogasawara, A. A., Iwasa, M. & Sekimizu, K. Establishment of a polymerase chain reaction-based method for strain-level management of Enterococcus faecalis EF-2001 using species-specific sequences identified by whole genome sequences. Front. Microbiol. 13, 959063. https:\/\/doi.org\/10.3389\/fmicb.2022.959063 (2022).","journal-title":"Front. Microbiol."},{"key":"62309_CR40","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1016\/j.ygeno.2021.03.021","volume":"113","author":"S Panthee","year":"2021","unstructured":"Panthee, S. et al. Complete genome sequence and comparative genomic analysis of Enterococcus faecalis EF-2001, a probiotic bacterium. Genomics 113, 1534\u20131542. https:\/\/doi.org\/10.1016\/j.ygeno.2021.03.021 (2021).","journal-title":"Genomics"},{"key":"62309_CR41","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.jpsychires.2022.01.047","volume":"148","author":"K Takahashi","year":"2022","unstructured":"Takahashi, K. et al. Antidepressant effects of Enterococcus faecalis 2001 through the regulation of prefrontal cortical myelination via the enhancement of CREB\/BDNF and NF-kappaB p65\/LIF\/STAT3 pathways in olfactory bulbectomized mice. J. Psychiatr. Res. 148, 137\u2013148. https:\/\/doi.org\/10.1016\/j.jpsychires.2022.01.047 (2022).","journal-title":"J. Psychiatr. Res."},{"key":"62309_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2020.112997","volume":"223","author":"K Takahashi","year":"2020","unstructured":"Takahashi, K. et al. Antidementia effects of Enterococcus faecalis 2001 are associated with enhancement of hippocampal neurogenesis via the ERK-CREB-BDNF pathway in olfactory bulbectomized mice. Physiol. Behav. 223, 112997. https:\/\/doi.org\/10.1016\/j.physbeh.2020.112997 (2020).","journal-title":"Physiol. Behav."},{"key":"62309_CR43","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1038\/s41598-018-20504-z","volume":"8","author":"A Belmer","year":"2018","unstructured":"Belmer, A., Patkar, O. L., Lanoue, V. & Bartlett, S. E. 5-HT1A receptor-dependent modulation of emotional and neurogenic deficits elicited by prolonged consumption of alcohol. Sci. Rep. 8, 2099. https:\/\/doi.org\/10.1038\/s41598-018-20504-z (2018).","journal-title":"Sci. Rep."},{"key":"62309_CR44","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3389\/fnbeh.2018.00058","volume":"12","author":"KD Nyuyki","year":"2018","unstructured":"Nyuyki, K. D., Cluny, N. L., Swain, M. G., Sharkey, K. A. & Pittman, Q. J. Altered brain excitability and increased anxiety in mice with experimental colitis: Consideration of hyperalgesia and sex differences. Front. Behav. Neurosci. 12, 58. https:\/\/doi.org\/10.3389\/fnbeh.2018.00058 (2018).","journal-title":"Front. Behav. Neurosci."},{"key":"62309_CR45","first-page":"238","volume":"69","author":"HS Cooper","year":"1993","unstructured":"Cooper, H. S., Murthy, S. N., Shah, R. S. & Sedergran, D. J. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Investig. 69, 238\u2013249 (1993).","journal-title":"Lab Investig."},{"key":"62309_CR46","doi-asserted-by":"publisher","first-page":"3642","DOI":"10.3748\/wjg.v16.i29.3642","volume":"16","author":"V Vasina","year":"2010","unstructured":"Vasina, V. et al. Non-peptidyl low molecular weight radical scavenger IAC attenuates DSS-induced colitis in rats. World J. Gastroenterol. 16, 3642\u20133650. https:\/\/doi.org\/10.3748\/wjg.v16.i29.3642 (2010).","journal-title":"World J. Gastroenterol."},{"key":"62309_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2021.136340","volume":"766","author":"H Kimijima","year":"2022","unstructured":"Kimijima, H. et al. Trichostatin A, a histone deacetylase inhibitor, alleviates the emotional abnormality induced by maladaptation to stress in mice. Neurosci. Lett. 766, 136340. https:\/\/doi.org\/10.1016\/j.neulet.2021.136340 (2022).","journal-title":"Neurosci. Lett."},{"key":"62309_CR48","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2021.105213","volume":"151","author":"K Kurokawa","year":"2021","unstructured":"Kurokawa, K. et al. Activation of 5-HT(1A) receptor reduces abnormal emotionality in stress-maladaptive mice by alleviating decreased myelin protein in the ventral hippocampus. Neurochem. Int. 151, 105213. https:\/\/doi.org\/10.1016\/j.neuint.2021.105213 (2021).","journal-title":"Neurochem. Int."},{"key":"62309_CR49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neuroscience.2020.08.030","volume":"446","author":"K Kurokawa","year":"2020","unstructured":"Kurokawa, K. et al. Leukemia inhibitory factor participates in the formation of stress adaptation via hippocampal myelination in mice. Neuroscience 446, 1\u201313. https:\/\/doi.org\/10.1016\/j.neuroscience.2020.08.030 (2020).","journal-title":"Neuroscience"},{"key":"62309_CR50","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/s0014-2999(98)00223-4","volume":"350","author":"H Takeda","year":"1998","unstructured":"Takeda, H., Tsuji, M. & Matsumiya, T. Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and\/or anxiolytic state in mice. Eur. J. Pharmacol. 350, 21\u201329. https:\/\/doi.org\/10.1016\/s0014-2999(98)00223-4 (1998).","journal-title":"Eur. J. Pharmacol."},{"key":"62309_CR51","volume-title":"The Mouse Brain in Stereotaxic Coordinates","author":"G Paxinos","year":"2001","unstructured":"Paxinos, G. & Franklin, K. B. J. The Mouse Brain in Stereotaxic Coordinates (Academic Press, 2001)."},{"key":"62309_CR52","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.jphs.2018.06.006","volume":"137","author":"K Takahashi","year":"2018","unstructured":"Takahashi, K. et al. Antidepressant-like effect of aripiprazole via 5-HT1A, D1, and D2 receptors in the prefrontal cortex of olfactory bulbectomized mice. J. Pharmacol. Sci. 137, 241\u2013247. https:\/\/doi.org\/10.1016\/j.jphs.2018.06.006 (2018).","journal-title":"J. Pharmacol. Sci."},{"key":"62309_CR53","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2020.147015","volume":"1746","author":"K Takahashi","year":"2020","unstructured":"Takahashi, K. et al. Dopamine D2 receptor supersensitivity in the hypothalamus of olfactory bulbectomized mice. Brain Res. 1746, 147015. https:\/\/doi.org\/10.1016\/j.brainres.2020.147015 (2020).","journal-title":"Brain Res."},{"key":"62309_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2021.105112","volume":"148","author":"K Takahashi","year":"2021","unstructured":"Takahashi, K. et al. Disturbance of prefrontal cortical myelination in olfactory bulbectomized mice is associated with depressive-like behavior. Neurochem. Int. 148, 105112. https:\/\/doi.org\/10.1016\/j.neuint.2021.105112 (2021).","journal-title":"Neurochem. Int."},{"key":"62309_CR55","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2022.110666","volume":"121","author":"K Takahashi","year":"2023","unstructured":"Takahashi, K. et al. Brexpiprazole prevents colitis-induced depressive-like behavior through myelination in the prefrontal cortex. Prog. Neuropsychopharmacol. Biol. Psychiatry 121, 110666. https:\/\/doi.org\/10.1016\/j.pnpbp.2022.110666 (2023).","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"62309_CR56","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.neures.2022.06.001","volume":"182","author":"K Takahashi","year":"2022","unstructured":"Takahashi, K. et al. Correlation between the reduction in hippocampal SirT2 expression and depressive-like behaviors and neurological abnormalities in olfactory bulbectomized mice. Neurosci. Res. 182, 76\u201380. https:\/\/doi.org\/10.1016\/j.neures.2022.06.001 (2022).","journal-title":"Neurosci. Res."},{"key":"62309_CR57","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1002\/hup.1105","volume":"25","author":"M Takahashi","year":"2010","unstructured":"Takahashi, M. et al. The effects of acute treatment with tandospirone, diazepam, and placebo on driving performance and cognitive function in healthy volunteers. Hum. Psychopharmacol. 25, 260\u2013267. https:\/\/doi.org\/10.1002\/hup.1105 (2010).","journal-title":"Hum. Psychopharmacol."},{"key":"62309_CR58","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.expneurol.2017.04.017","volume":"299","author":"C Nicolini","year":"2018","unstructured":"Nicolini, C. & Fahnestock, M. The valproic acid-induced rodent model of autism. Exp. Neurol. 299, 217\u2013227. https:\/\/doi.org\/10.1016\/j.expneurol.2017.04.017 (2018).","journal-title":"Exp. Neurol."},{"key":"62309_CR59","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1007\/s11920-003-0056-7","volume":"5","author":"JD Uys","year":"2003","unstructured":"Uys, J. D., Stein, D. J., Daniels, W. M. & Harvey, B. H. Animal models of anxiety disorders. Curr. Psychiatry Rep. 5, 274\u2013281. https:\/\/doi.org\/10.1007\/s11920-003-0056-7 (2003).","journal-title":"Curr. Psychiatry Rep."},{"key":"62309_CR60","doi-asserted-by":"publisher","first-page":"341","DOI":"10.9758\/cpn.2020.18.3.341","volume":"18","author":"D Sarkar","year":"2020","unstructured":"Sarkar, D. A review of behavioral tests to evaluate different types of anxiety and anti-anxiety effects. Clin. Psychopharmacol. Neurosci. 18, 341\u2013351. https:\/\/doi.org\/10.9758\/cpn.2020.18.3.341 (2020).","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"62309_CR61","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1078\/0940-2993-00301","volume":"55","author":"T Karl","year":"2003","unstructured":"Karl, T., Pabst, R. & von H\u00f6rsten, S. Behavioral phenotyping of mice in pharmacological and toxicological research. Exp. Toxicol. Pathol. 55, 69\u201383. https:\/\/doi.org\/10.1078\/0940-2993-00301 (2003).","journal-title":"Exp. Toxicol. Pathol."},{"key":"62309_CR62","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.scib.2021.09.007","volume":"67","author":"X Qin","year":"2022","unstructured":"Qin, X. et al. GABA(A)(\u03b4) receptor hypofunction in the amygdala-hippocampal circuit underlies stress-induced anxiety. Sci. Bull. (Beijing) 67, 97\u2013110. https:\/\/doi.org\/10.1016\/j.scib.2021.09.007 (2022).","journal-title":"Sci. Bull. (Beijing)"},{"key":"62309_CR63","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1037\/0735-7044.118.1.63","volume":"118","author":"SB McHugh","year":"2004","unstructured":"McHugh, S. B., Deacon, R. M., Rawlins, J. N. & Bannerman, D. M. Amygdala and ventral hippocampus contribute differentially to mechanisms of fear and anxiety. Behav. Neurosci. 118, 63\u201378. https:\/\/doi.org\/10.1037\/0735-7044.118.1.63 (2004).","journal-title":"Behav. Neurosci."},{"key":"62309_CR64","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.neulet.2012.03.091","volume":"516","author":"I Aksu","year":"2012","unstructured":"Aksu, I. et al. Maternal treadmill exercise during pregnancy decreases anxiety and increases prefrontal cortex VEGF and BDNF levels of rat pups in early and late periods of life. Neurosci. Lett. 516, 221\u2013225. https:\/\/doi.org\/10.1016\/j.neulet.2012.03.091 (2012).","journal-title":"Neurosci. Lett."},{"key":"62309_CR65","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2021.113165","volume":"404","author":"R Al\u00f2","year":"2021","unstructured":"Al\u00f2, R. et al. Correlation of distinct behaviors to the modified expression of cerebral Shank 1,3 and BDNF in two autistic animal models. Behav. Brain Res. 404, 113165. https:\/\/doi.org\/10.1016\/j.bbr.2021.113165 (2021).","journal-title":"Behav. Brain Res."},{"key":"62309_CR66","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054811","volume":"8","author":"F Reichmann","year":"2013","unstructured":"Reichmann, F., Painsipp, E. & Holzer, P. Environmental enrichment and gut inflammation modify stress-induced c-Fos expression in the mouse corticolimbic system. PLoS One 8, e54811. https:\/\/doi.org\/10.1371\/journal.pone.0054811 (2013).","journal-title":"PLoS One"},{"key":"62309_CR67","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/j.bbrc.2020.09.106","volume":"533","author":"Q Xiao","year":"2020","unstructured":"Xiao, Q., Xu, X. & Tu, J. Chronic optogenetic manipulation of basolateral amygdala astrocytes rescues stress-induced anxiety. Biochem. Biophys. Res. Commun. 533, 657\u2013664. https:\/\/doi.org\/10.1016\/j.bbrc.2020.09.106 (2020).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"62309_CR68","doi-asserted-by":"publisher","first-page":"61","DOI":"10.31083\/j.jin2102061","volume":"21","author":"A Zahra","year":"2022","unstructured":"Zahra, A. et al. Prenatal exposure of citalopram elicits depression-like and anxiety-like behaviors and alteration of morphology and protein expression of medial prefrontal cortex in young adult mice. J. Integr. Neurosci. 21, 61. https:\/\/doi.org\/10.31083\/j.jin2102061 (2022).","journal-title":"J. Integr. Neurosci."},{"key":"62309_CR69","doi-asserted-by":"publisher","first-page":"1123","DOI":"10.1007\/s11064-016-2146-z","volume":"42","author":"TT Zhao","year":"2017","unstructured":"Zhao, T. T. et al. Effects of (\u2013)-sesamin on chronic stress-induced anxiety disorders in mice. Neurochem. Res. 42, 1123\u20131129. https:\/\/doi.org\/10.1007\/s11064-016-2146-z (2017).","journal-title":"Neurochem. Res."},{"key":"62309_CR70","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108682","volume":"195","author":"Y Liu","year":"2021","unstructured":"Liu, Y., Sanderson, D., Mian, M. F., McVey Neufeld, K. A. & Forsythe, P. Loss of vagal integrity disrupts immune components of the microbiota\u2013gut\u2013brain axis and inhibits the effect of Lactobacillus rhamnosus on behavior and the corticosterone stress response. Neuropharmacology 195, 108682. https:\/\/doi.org\/10.1016\/j.neuropharm.2021.108682 (2021).","journal-title":"Neuropharmacology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-62309-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-62309-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-62309-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T22:03:00Z","timestamp":1716242580000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-024-62309-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,21]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["62309"],"URL":"https:\/\/doi.org\/10.1038\/s41598-024-62309-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,21]]},"assertion":[{"value":"5 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 May 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 May 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Masahiro Iwasa, Hiroyuki Iwasa, and Shigeo Suzuki are employees of Nihon Berm Co., Ltd. All other authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"11519"}}