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Both conditions strongly worsen IBD disease burden. In the present review, we summarize the current understanding of the pathogenesis of depression and anxiety in IBD. We present a stepwise cascade along a gut\u2013immune\u2013brain axis initiated by evasion of chronic intestinal inflammation to pass the epithelial and vascular barrier in the gut and cause systemic inflammation. We then summarize different anatomical transmission routes of gut-derived peripheral inflammation into the central nervous system (CNS) and highlight the current knowledge on neuroinflammatory changes in the CNS of preclinical IBD mouse models with a focus on microglia, the brain-resident macrophages. Subsequently, we discuss how neuroinflammation in IBD can alter neuronal circuitry to trigger symptoms like depression and anxiety. Finally, the role of intestinal microbiota in the gut\u2013immune\u2013brain axis in IBD will be reviewed. A more comprehensive understanding of the interaction between the gastrointestinal tract, the immune system and the CNS accounting for the similarities and differences between UC and CD will pave the path for improved prediction and treatment of neuropsychiatric comorbidities in IBD and other inflammatory diseases.<\/jats:p>","DOI":"10.3390\/ijms231911111","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T01:47:06Z","timestamp":1663811226000},"page":"11111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":79,"title":["The Gut\u2013Immune\u2013Brain Axis: An Important Route for Neuropsychiatric Morbidity in Inflammatory Bowel Disease"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1181-5048","authenticated-orcid":false,"given":"Rebecca Katharina","family":"Masanetz","sequence":"first","affiliation":[{"name":"Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0630-9204","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beate","family":"Winner","sequence":"additional","affiliation":[{"name":"Department of Stem Cell Biology, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"},{"name":"Center of Rare Diseases Erlangen (ZSEER), University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"},{"name":"Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum Immuntherapie (DZI), Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"},{"name":"Department of Internal Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"S\u00fc\u00df","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"},{"name":"Department of Neurology, University Hospital Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (FAU), 91054 Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/S2468-1253(19)30358-9","article-title":"Global burden of inflammatory bowel disease","volume":"5","author":"Jairath","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S2468-1253(19)30333-4","article-title":"The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"5","author":"Alatab","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1016\/S0140-6736(17)32448-0","article-title":"Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: A systematic review of population-based studies","volume":"390","author":"Ng","year":"2017","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S2468-1253(21)00014-5","article-title":"Prevalence of symptoms of anxiety and depression in patients with inflammatory bowel disease: A systematic review and meta-analysis","volume":"6","author":"Barberio","year":"2021","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1136\/gutjnl-2021-325985","article-title":"Bidirectional brain\u2013gut axis effects influence mood and prognosis in IBD: A systematic review and meta-analysis","volume":"71","author":"Fairbrass","year":"2021","journal-title":"Gut"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1093\/ecco-jcc\/jjab191","article-title":"Depression and Inflammatory Bowel Disease: A Bidirectional Two-sample Mendelian Randomization Study","volume":"16","author":"Luo","year":"2021","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/mp.2016.167","article-title":"Antidepressant activity of anti-cytokine treatment: A systematic review and meta-analysis of clinical trials of chronic inflammatory conditions","volume":"23","author":"Kappelmann","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1038\/s41380-019-0471-8","article-title":"Effects of immunomodulatory drugs on depressive symptoms: A mega-analysis of randomized, placebo-controlled clinical trials in inflammatory disorders","volume":"25","author":"Wittenberg","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s10620-014-3375-0","article-title":"Treatment with Immunosuppressive Therapy May Improve Depressive Symptoms in Patients with Inflammatory Bowel Disease","volume":"60","author":"Horst","year":"2015","journal-title":"Dig. Dis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yeshi, K., Ruscher, R., Hunter, L., Daly, N.L., Loukas, A., and Wangchuk, P. (2020). Revisiting Inflammatory Bowel Disease: Pathology, Treatments, Challenges and Emerging Therapeutics Including Drug Leads from Natural Products. J. Clin. Med., 9.","DOI":"10.3390\/jcm9051273"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1053\/j.sempedsurg.2017.10.003","article-title":"Clinical presentation of Crohn\u2019s, ulcerative colitis, and indeterminate colitis: Symptoms, extraintestinal manifestations, and disease phenotypes","volume":"26","author":"Yu","year":"2017","journal-title":"Semin. Pediatr. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1093\/ibd\/izz076","article-title":"Challenges in IBD Research: Environmental Triggers","volume":"25","author":"Ho","year":"2019","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1310","DOI":"10.1053\/j.gastro.2019.07.031","article-title":"Interferon Lambda Promotes Paneth Cell Death via STAT1 Signaling in Mice and Is Increased in Inflamed Ileal Tissues of Patients with Crohn\u2019s Disease","volume":"157","author":"Ruder","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1093\/ibd\/izz142","article-title":"Environmental Microbial Factors Determine the Pattern of Inflammatory Lesions in a Murine Model of Crohn\u2019s Disease\u2013Like Inflammation","volume":"26","author":"Stolzer","year":"2019","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/ng.3760","article-title":"Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease","volume":"49","author":"Moutsianas","year":"2017","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/s41586-021-04006-z","article-title":"Regulation of intestinal immunity and tissue repair by enteric glia","volume":"599","author":"Progatzky","year":"2021","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Acera, M.G., Bubeck, M., Mascia, F., Diemand, L., Sturm, G., K\u00fchl, A.A., Atreya, R., Lie, D.C., Neurath, M.F., and Schumann, M. (2021). Dynamic, Transient, and Robust Increase in the Innervation of the Inflamed Mucosa in Inflammatory Bowel Diseases. Cells, 10.","DOI":"10.3390\/cells10092253"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/nprot.2017.044","article-title":"Chemically induced mouse models of acute and chronic intestinal inflammation","volume":"12","author":"Wirtz","year":"2017","journal-title":"Nat. Protoc."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/ibd.20753","article-title":"Distinct Cytokine Patterns Identified from Multiplex Profiles of Murine DSS and TNBS-Induced Colitis","volume":"15","author":"Alex","year":"2009","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7479540","DOI":"10.1155\/2021\/7479540","article-title":"An Update of Research Animal Models of Inflammatory Bowel Disease","volume":"2021","author":"Baydi","year":"2021","journal-title":"Sci. World J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1007\/s10753-015-0180-7","article-title":"Sex Differences in Experimentally Induced Colitis in Mice: A Role for Estrogens","volume":"38","author":"Hodosy","year":"2015","journal-title":"Inflammation"},{"key":"ref_22","first-page":"G544","article-title":"Differential susceptibility of inbred mouse strains to dextran sulfate sodium-induced colitis","volume":"274","author":"Bristol","year":"1998","journal-title":"Am. J. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1538\/expanim.49.9","article-title":"Histological Analysis of Murine Colitis Induced by Dextran Sulfate Sodium of Different Molecular Weights","volume":"49","author":"Kitajima","year":"2000","journal-title":"Exp. Anim."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1007\/s12264-018-0288-5","article-title":"Cortical Inflammation is Increased in a DSS-Induced Colitis Mouse Model","volume":"34","author":"Han","year":"2018","journal-title":"Neurosci. Bull."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S1074-7613(00)80038-2","article-title":"Impaired On\/Off Regulation of TNF Biosynthesis in Mice Lacking TNF AU-Rich Elements: Implications for Joint and Gut-Associated Immunopathologies","volume":"10","author":"Kontoyiannis","year":"1999","journal-title":"Immunity"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nature10400","article-title":"Caspase-8 regulates TNF-\u03b1-induced epithelial necroptosis and terminal ileitis","volume":"477","author":"Martini","year":"2011","journal-title":"Nature"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1136\/gutjnl-2020-321339","article-title":"SETDB1 is required for intestinal epithelial differentiation and the prevention of intestinal inflammation","volume":"70","author":"Peuker","year":"2021","journal-title":"Gut"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nature10273","article-title":"FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation","volume":"477","author":"Welz","year":"2011","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s00281-014-0454-4","article-title":"The gut microbiota and inflammatory bowel disease","volume":"37","author":"Matsuoka","year":"2015","journal-title":"Semin. Immunopathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.chom.2014.02.005","article-title":"The treatment-naive microbiome in new-onset Crohn\u2019s disease","volume":"15","author":"Gevers","year":"2014","journal-title":"Cell Host Microbe"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/s41586-021-03531-1","article-title":"Thymic development of gut-microbiota-specific T cells","volume":"594","author":"Kim","year":"2021","journal-title":"Nat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1016\/j.cell.2009.09.033","article-title":"Induction of Intestinal Th17 Cells by Segmented Filamentous Bacteria","volume":"139","author":"Ivanov","year":"2009","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/s41575-019-0258-z","article-title":"Gut microbiota-derived metabolites as key actors in inflammatory bowel disease","volume":"17","author":"Lavelle","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2174\/1874091X01004010053","article-title":"The Impact of the Level of the Intestinal Short Chain Fatty Acids in Inflammatory Bowel Disease Patients Versus Healthy Subjects","volume":"4","author":"Faujan","year":"2010","journal-title":"Open Biochem. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1111\/1751-7915.13583","article-title":"Pediococcus pentosaceus LI05 alleviates DSS-induced colitis by modulating immunological profiles, the gut microbiota and short-chain fatty acid levels in a mouse model","volume":"13","author":"Bian","year":"2020","journal-title":"Microb. Biotechnol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1016\/j.chom.2019.10.009","article-title":"Whole-Virome Analysis Sheds Light on Viral Dark Matter in Inflammatory Bowel Disease","volume":"26","author":"Clooney","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.chom.2020.08.003","article-title":"The Gut Virome Database Reveals Age-Dependent Patterns of Virome Diversity in the Human Gut","volume":"28","author":"Gregory","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41564-021-01020-9","article-title":"A catalogue of 1167 genomes from the human gut archaeome","volume":"7","author":"Chibani","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1111\/myc.13238","article-title":"Gut mycobiome: The probable determinative role of fungi in IBD patients","volume":"64","author":"Shahrokh","year":"2021","journal-title":"Mycoses"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"641483","DOI":"10.3389\/fmicb.2021.641483","article-title":"Blastocystis Colonization Alters the Gut Microbiome and, in Some Cases, Promotes Faster Recovery from Induced Colitis","volume":"12","author":"Billy","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"myab076","DOI":"10.1093\/mmy\/myab076","article-title":"Intestinal mycobiome associated with diagnosis of inflammatory bowel disease based on tissue biopsies","volume":"60","author":"Riegert","year":"2022","journal-title":"Med. Mycol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.cell.2022.01.017","article-title":"Mucosal fungi promote gut barrier function and social behavior via Type 17 immunity","volume":"185","author":"Leonardi","year":"2022","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1038\/s41586-022-04502-w","article-title":"Immune regulation by fungal strain diversity in inflammatory bowel disease","volume":"603","author":"Li","year":"2022","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1987779","DOI":"10.1080\/19490976.2021.1987779","article-title":"Depression and anxiety in patients with active ulcerative colitis: Crosstalk of gut microbiota, metabolomics and proteomics","volume":"13","author":"Yuan","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1053\/j.gastro.2021.07.026","article-title":"Systemic Inflammation in Preclinical Ulcerative Colitis","volume":"161","author":"Bergemalm","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1093\/rheumatology\/keaa164","article-title":"Gut epithelial impairment, microbial translocation and immune system activation in inflammatory bowel disease-associated spondyloarthritis","volume":"60","author":"Luchetti","year":"2021","journal-title":"Rheumatology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1136\/gutjnl-2018-317571","article-title":"Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis","volume":"68","author":"Jabbar","year":"2019","journal-title":"Gut"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12974-021-02354-1","article-title":"Neuroinflammation as an etiological trigger for depression comorbid with inflammatory bowel disease","volume":"19","author":"Craig","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2232","DOI":"10.1136\/gutjnl-2020-322260","article-title":"Mucus barrier, mucins and gut microbiota: The expected slimy partners?","volume":"69","author":"Paone","year":"2020","journal-title":"Gut"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/s12276-021-00617-8","article-title":"Slimy partners: The mucus barrier and gut microbiome in ulcerative colitis","volume":"53","author":"Fang","year":"2021","journal-title":"Exp. Mol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4691","DOI":"10.1172\/JCI124884","article-title":"IFN-\u03b3 drives inflammatory bowel disease pathogenesis through VE-cadherin\u2013directed vascular barrier disruption","volume":"129","author":"Langer","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1126\/science.aad0135","article-title":"A gut-vascular barrier controls the systemic dissemination of bacteria","volume":"350","author":"Spadoni","year":"2015","journal-title":"Science"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1126\/science.abc6108","article-title":"Identification of a choroid plexus vascular barrier closing during intestinal inflammation","volume":"374","author":"Carloni","year":"2021","journal-title":"Science"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"611764","DOI":"10.3389\/fncel.2020.611764","article-title":"Hypoxia Augments Cerebral Inflammation in a Dextran Sulfate Sodium-Induced Colitis Mouse Model","volume":"14","author":"Han","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"118587","DOI":"10.1016\/j.lfs.2020.118587","article-title":"Changes in serum inflammatory cytokine levels and intestinal flora in a self-healing dextran sodium sulfate-induced ulcerative colitis murine model","volume":"263","author":"Jialing","year":"2020","journal-title":"Life Sci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1186\/s12974-021-02317-6","article-title":"DSS-induced inflammation in the colon drives a proinflammatory signature in the brain that is ameliorated by prophylactic treatment with the S100A9 inhibitor paquinimod","volume":"18","author":"Talley","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"G837","DOI":"10.1152\/ajpgi.00061.2021","article-title":"Vitamin D\/VDR signaling inhibits colitis by suppressing HIF-1\u03b1 activation in colonic epithelial cells","volume":"320","author":"Xue","year":"2021","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"609689","DOI":"10.3389\/fimmu.2020.609689","article-title":"Local Stabilization of Hypoxia-Inducible Factor-1\u03b1 Controls Intestinal Inflammation via Enhanced Gut Barrier Function and Immune Regulation","volume":"11","author":"Kim","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ajpath.2021.09.006","article-title":"Chronic Intestinal Inflammation Suppresses Brain Activity by Inducing Neuroinflammation in Mice","volume":"192","author":"Mitchell","year":"2022","journal-title":"Am. J. Pathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1038\/s41380-020-0651-6","article-title":"Hippocampal neural stem cells and microglia response to experimental inflammatory bowel disease (IBD)","volume":"26","author":"Gampierakis","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1186\/s12974-021-02262-4","article-title":"Brain profiling in murine colitis and human epilepsy reveals neutrophils and TNF\u03b1 as mediators of neuronal hyperexcitability","volume":"18","author":"Barnes","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"G361","DOI":"10.1152\/ajpgi.00177.2020","article-title":"A murine model of pediatric inflammatory bowel disease causes microbiota-gut-brain axis deficits in adulthood","volume":"319","author":"Salvo","year":"2020","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"20217","DOI":"10.1038\/s41598-019-56859-0","article-title":"Experimental colitis reduces microglial cell activation in the mouse brain without affecting microglial cell numbers","volume":"9","author":"Sroor","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1186\/s12974-021-02199-8","article-title":"Chronic colitis exacerbates NLRP3-dependent neuroinflammation and cognitive impairment in middle-aged brain","volume":"18","author":"He","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s12974-015-0281-0","article-title":"Chronic intestinal inflammation alters hippocampal neurogenesis","volume":"12","author":"Zonis","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.3233\/JAD-201099","article-title":"Gut Inflammation Induced by Dextran Sulfate Sodium Exacerbates Amyloid-\u03b2 Plaque Deposition in the AppNL-G-F Mouse Model of Alzheimer\u2019s Disease","volume":"79","author":"Sohrabi","year":"2021","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"112640","DOI":"10.1016\/j.bbr.2020.112640","article-title":"Liver hydrolysate prevents depressive-like behavior in an animal model of colitis: Involvement of hippocampal neurogenesis via the AMPK\/BDNF pathway","volume":"390","author":"Nakagawasai","year":"2020","journal-title":"Behav. Brain Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1016\/j.bbi.2019.05.007","article-title":"Persistent central inflammation and region specific cellular activation accompany depression- and anxiety-like behaviours during the resolution phase of experimental colitis","volume":"80","author":"Dempsey","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.neuroscience.2017.10.023","article-title":"Anxiety- and Depressive-Like Behaviors are Associated with Altered Hippocampal Energy and Inflammatory Status in a Mouse Model of Crohn\u2019s Disease","volume":"366","author":"Amiri","year":"2017","journal-title":"Neuroscience"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.pnpbp.2015.08.004","article-title":"Behavioral despair associated with a mouse model of Crohn\u2019s disease: Role of nitric oxide pathway","volume":"64","author":"Heydarpour","year":"2016","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"17151","DOI":"10.1073\/pnas.0806682105","article-title":"Microglial activation and TNFalpha production mediate altered CNS excitability following peripheral inflammation","volume":"105","author":"Riazi","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4137\/CGast.S20612","article-title":"Characterization of Serum Cytokine Profile in Predominantly Colonic Inflammatory Bowel Disease to Delineate Ulcerative and Crohn\u2019s Colitides","volume":"8","author":"Korolkova","year":"2015","journal-title":"Clin. Med. Insights Gastroenterol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"14638","DOI":"10.1038\/s41598-020-71503-y","article-title":"Serological cytokine signature in paediatric patients with inflammatory bowel disease impacts diagnosis","volume":"10","author":"Tatsuki","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3389\/fpsyt.2018.00044","article-title":"Vagus Nerve as Modulator of the Brain\u2013Gut Axis in Psychiatric and Inflammatory Disorders","volume":"9","author":"Breit","year":"2018","journal-title":"Front. Psychiatry"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1038\/s41586-021-04359-5","article-title":"Sensory representation and detection mechanisms of gut osmolality change","volume":"602","author":"Ichiki","year":"2022","journal-title":"Nature"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.jnutbio.2018.03.009","article-title":"Short-chain fatty acids suppress food intake by activating vagal afferent neurons","volume":"57","author":"Goswami","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1053\/j.gastro.2016.10.046","article-title":"The Vagus Nerve in Appetite Regulation, Mood, and Intestinal Inflammation","volume":"152","author":"Browning","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"7","DOI":"10.15424\/bioelectronmed.2016.00007","article-title":"Cytokine-specific Neurograms in the Sensory Vagus Nerve","volume":"3","author":"Steinberg","year":"2016","journal-title":"Bioelectron. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0304-3940(94)11105-R","article-title":"Blockade of interleukin-1 induced hyperthermia by subdiaphragmatic vagotomy: Evidence for vagal mediation of immune-brain communication","volume":"183","author":"Watkins","year":"1995","journal-title":"Neurosci. Lett."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2102","DOI":"10.1053\/j.gastro.2010.06.063","article-title":"Chronic Gastrointestinal Inflammation Induces Anxiety-Like Behavior and Alters Central Nervous System Biochemistry in Mice","volume":"139","author":"Bercik","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Sun, P., Zhou, K., Wang, S., Li, P., Chen, S., Lin, G., Zhao, Y., and Wang, T. (2013). Involvement of MAPK\/NF-\u03baB signaling in the activation of the cholinergic anti-inflammatory pathway in experimental colitis by chronic vagus nerve stimulation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069424"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e13911","DOI":"10.1111\/nmo.13911","article-title":"A 12-month pilot study outcomes of vagus nerve stimulation in Crohn\u2019s disease","volume":"32","author":"Sinniger","year":"2020","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1136\/gut.2009.190439","article-title":"TNI\u00b1 is a key mediator of the pronociceptive effects of mucosal supernatant from human ulcerative colitis on colonic DRG neurons","volume":"59","author":"Ibeakanma","year":"2010","journal-title":"Gut"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1053\/j.gastro.2015.05.063","article-title":"Functional Brain Imaging Reveals Rapid Blockade of Abdominal Pain Response Upon Anti-TNF Therapy in Crohn\u2019s Disease","volume":"149","author":"Hess","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1038\/ni.3666","article-title":"The movers and shapers in immune privilege of the CNS","volume":"18","author":"Engelhardt","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1038\/s41423-021-00757-x","article-title":"The blood\u2013brain barrier in systemic infection and inflammation","volume":"18","author":"Galea","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbi.2016.03.010","article-title":"The blood-brain barrier in systemic inflammation","volume":"60","author":"Varatharaj","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_88","first-page":"5664","article-title":"Elevation of arachidonoylethanolamide levels by activation of the endocannabinoid system protects against colitis and ameliorates remote organ lesions in mice","volume":"14","author":"Zhao","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"G1174","DOI":"10.1152\/ajpgi.1999.276.5.G1174","article-title":"Experimental colitis increases blood-brain barrier permeability in rabbits","volume":"276","author":"Hathaway","year":"1999","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1111\/j.1365-2982.2005.00654.x","article-title":"Disruption of the blood-brain barrier during TNBS colitis","volume":"17","author":"Natah","year":"2005","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.immuni.2016.04.005","article-title":"Brain Endothelial- and Epithelial-Specific Interferon Receptor Chain 1 Drives Virus-Induced Sickness Behavior and Cognitive Impairment","volume":"44","author":"Blank","year":"2016","journal-title":"Immunity"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/s41591-019-0440-4","article-title":"Aged blood impairs hippocampal neural precursor activity and activates microglia via brain endothelial cell VCAM1","volume":"25","author":"Yousef","year":"2019","journal-title":"Nat. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"102926","DOI":"10.1016\/j.nicl.2021.102926","article-title":"Choroid plexus enlargement is associated with neuroinflammation and reduction of blood brain barrier permeability in depression","volume":"33","author":"Althubaity","year":"2022","journal-title":"NeuroImage Clin."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.15252\/emmm.201606271","article-title":"Identification of a novel mechanism of blood\u2013brain communication during peripheral inflammation via choroid plexus\u2014derived extracellular vesicles","volume":"8","author":"Balusu","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1038\/s41593-019-0393-4","article-title":"A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment","volume":"22","author":"Martens","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1126\/science.1252945","article-title":"Aging-induced type I interferon response at the choroid plexus negatively affects brain function","volume":"346","author":"Baruch","year":"2014","journal-title":"Science"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nature18626","article-title":"Unexpected role of interferon-\u03b3 in regulating neuronal connectivity and social behaviour","volume":"535","author":"Filiano","year":"2016","journal-title":"Nature"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1038\/s41590-020-0776-4","article-title":"Meningeal \u03b3\u03b4 T cells regulate anxiety-like behavior via IL-17a signaling in neurons","volume":"21","author":"Rustenhoven","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.bbi.2021.05.008","article-title":"Stroke affects intestinal immune cell trafficking to the central nervous system","volume":"96","author":"Brea","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Kivis\u00e4kk, P., Tucky, B., Wei, T., Campbell, J.J., and Ransohoff, R.M. (2006). Human cerebrospinal fluid contains CD4+ memory T cells expressing gut- or skin-specific trafficking determinants: Relevance for immunotherapy. BMC Immunol., 7.","DOI":"10.1186\/1471-2172-7-14"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1038\/s41583-018-0055-7","article-title":"Inflammasome signalling in brain function and neurodegenerative disease","volume":"19","author":"Heneka","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.ajpath.2021.10.013","article-title":"Experimental Colitis Enhances Temporal Variations in CX3CR1 Cell Colonization of the Gut and Brain Following Irradiation","volume":"192","author":"Batra","year":"2022","journal-title":"Am. J. Pathol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"9970","DOI":"10.1038\/srep09970","article-title":"Dextran sulfate sodium-induced colitis alters stress-associated behaviour and neuropeptide gene expression in the amygdala-hippocampus network of mice","volume":"5","author":"Reichmann","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic reactive astrocytes are induced by activated microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"108546","DOI":"10.1016\/j.intimp.2022.108546","article-title":"Systemic sterile induced-co-expression of IL-12 and IL-18 drive IFN-\u03b3-dependent activation of microglia and recruitment of MHC-II-expressing inflammatory monocytes into the brain","volume":"105","author":"Gaviglio","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1523\/JNEUROSCI.3567-08.2009","article-title":"Cerebral Microglia Recruit Monocytes into the Brain in Response to Tumor Necrosis Factor Signaling during Peripheral Organ Inflammation","volume":"29","author":"Le","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"4082","DOI":"10.1016\/j.celrep.2020.02.109","article-title":"Chronic Peripheral Inflammation Causes a Region-Specific Myeloid Response in the Central Nervous System","volume":"30","author":"Hoffmann","year":"2020","journal-title":"Cell Rep."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.bbi.2022.03.001","article-title":"Colitis-associated microbiota drives changes in behaviour in male mice in the absence of inflammation","volume":"102","author":"Vicentini","year":"2022","journal-title":"Brain Behav. Immun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41586-020-2777-8","article-title":"Negative feedback control of neuronal activity by microglia","volume":"586","author":"Badimon","year":"2020","journal-title":"Nature"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1016\/j.cell.2013.11.030","article-title":"Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor","volume":"155","author":"Parkhurst","year":"2013","journal-title":"Cell"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.cell.2020.06.026","article-title":"Microglia Require CD4 T Cells to Complete the Fetal-to-Adult Transition","volume":"182","author":"Pasciuto","year":"2020","journal-title":"Cell"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.immuni.2020.12.016","article-title":"Microglial activation elicits a negative affective state through prostaglandin-mediated modulation of striatal neurons","volume":"54","author":"Klawonn","year":"2021","journal-title":"Immunity"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1016\/j.neuron.2021.06.012","article-title":"Early-life inflammation promotes depressive symptoms in adolescence via microglial engulfment of dendritic spines","volume":"109","author":"Cao","year":"2021","journal-title":"Neuron"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.biopsych.2017.05.026","article-title":"Stress-Induced Neuronal Colony Stimulating Factor 1 Provokes Microglia-Mediated Neuronal Remodeling and Depressive-like Behavior","volume":"83","author":"Wohleb","year":"2018","journal-title":"Biol. Psychiatry"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.bbi.2021.10.009","article-title":"Microglial glutaminase 1 deficiency mitigates neuroinflammation associated depression","volume":"99","author":"Ji","year":"2022","journal-title":"Brain Behav. Immun."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.bbi.2020.11.008","article-title":"Ibrutinib alleviates LPS-induced neuroinflammation and synaptic defects in a mouse model of depression","volume":"92","author":"Li","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.bbi.2017.03.002","article-title":"NLRP3 inflammasome-driven pathways in depression: Clinical and preclinical findings","volume":"64","author":"Kaufmann","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12974-022-02400-6","article-title":"Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1\/Nrf2\/HO-1\/Gpx4 pathway","volume":"19","author":"Dang","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"96","DOI":"10.3389\/fnmol.2020.00096","article-title":"Melatonin Act as an Antidepressant via Attenuation of Neuroinflammation by Targeting Sirt1\/Nrf2\/HO-1 Signaling","volume":"13","author":"Ali","year":"2020","journal-title":"Front. Mol. Neurosci."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"3326","DOI":"10.1073\/pnas.1914655117","article-title":"Molecular adaptations of the blood-brain barrier promote stress resilience vs. depression","volume":"117","author":"Dudek","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1038\/s41593-017-0010-3","article-title":"Social stress induces neurovascular pathology promoting depression","volume":"20","author":"Menard","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1038\/mp.2017.64","article-title":"Microglial recruitment of IL-1\u03b2-producing monocytes to brain endothelium causes stress-induced anxiety","volume":"23","author":"McKim","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.bbi.2020.11.007","article-title":"Neuroinflammation induces anxiety- and depressive-like behavior by modulating neuronal plasticity in the basolateral amygdala","volume":"91","author":"Zheng","year":"2021","journal-title":"Brain Behav. Immun."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1053\/j.gastro.2009.08.041","article-title":"Serotonin has a key role in pathogenesis of experimental colitis","volume":"137","author":"Ghia","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1021\/acschemneuro.6b00414","article-title":"Diverse Effects of Gut-Derived Serotonin in Intestinal Inflammation","volume":"8","author":"Shajib","year":"2017","journal-title":"ACS Chem. Neurosci."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1093\/ibd\/izy367","article-title":"The Influence of Antidepressants on the Disease Course among Patients with Crohn\u2019s Disease and Ulcerative Colitis-A Danish Nationwide Register-Based Cohort Study","volume":"25","author":"Kristensen","year":"2019","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1186\/s12974-021-02175-2","article-title":"Tryptophan-kynurenine metabolism: A link between the gut and brain for depression in inflammatory bowel disease","volume":"18","author":"Chen","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"29","DOI":"10.2174\/1567205017666200212155234","article-title":"Microglia in Alzheimer\u2019s Disease","volume":"17","author":"Schlachetzki","year":"2020","journal-title":"Curr. Alzheimer Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.bbi.2018.03.004","article-title":"Complement component 3a receptor deficiency attenuates chronic stress-induced monocyte infiltration and depressive-like behavior","volume":"70","author":"Crider","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"110600","DOI":"10.1016\/j.celrep.2022.110600","article-title":"Early stress-induced impaired microglial pruning of excitatory synapses on immature CRH-expressing neurons provokes aberrant adult stress responses","volume":"38","author":"Bolton","year":"2022","journal-title":"Cell Rep."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/j.cell.2014.02.029","article-title":"SnapShot: Adult Hippocampal Neurogenesis","volume":"156","author":"Vadodaria","year":"2014","journal-title":"Cell"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/sj.mp.4000712","article-title":"Adult brain neurogenesis and psychiatry: A novel theory of depression","volume":"5","author":"Jacobs","year":"2000","journal-title":"Mol. Psychiatry"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41380-018-0036-2","article-title":"The role of adult hippocampal neurogenesis in brain health and disease","volume":"24","author":"Toda","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.stem.2010.08.014","article-title":"Microglia Shape Adult Hippocampal Neurogenesis through Apoptosis-Coupled Phagocytosis","volume":"7","author":"Sierra","year":"2010","journal-title":"Cell Stem Cell"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"9703","DOI":"10.1523\/JNEUROSCI.2723-06.2006","article-title":"Tumor Necrosis Factor Receptor 1 Is a Negative Regulator of Progenitor Proliferation in Adult Hippocampal Neurogenesis","volume":"26","author":"Iosif","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/sj.mp.4002055","article-title":"Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression","volume":"13","author":"Goshen","year":"2007","journal-title":"Mol. Psychiatry"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1760","DOI":"10.1126\/science.1088417","article-title":"Inflammatory Blockade Restores Adult Hippocampal Neurogenesis","volume":"302","author":"Monje","year":"2003","journal-title":"Science"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nature10357","article-title":"The ageing systemic milieu negatively regulates neurogenesis and cognitive function","volume":"477","author":"Villeda","year":"2011","journal-title":"Nature"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"112997","DOI":"10.1016\/j.physbeh.2020.112997","article-title":"Antidementia effects of Enterococcus faecalis 2001 are associated with enhancement of hippocampal neurogenesis via the ERK-CREB-BDNF pathway in olfactory bulbectomized mice","volume":"223","author":"Takahashi","year":"2020","journal-title":"Physiol. Behav."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nrn3379","article-title":"Neurotrophin regulation of neural circuit development and function","volume":"14","author":"Park","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1016\/j.cell.2021.01.034","article-title":"Antidepressant drugs act by directly binding to TRKB neurotrophin receptors","volume":"184","author":"Casarotto","year":"2021","journal-title":"Cell"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/S0306-4522(03)00564-5","article-title":"Brain-derived neurotrophic factor mRNA downregulation produced by social isolation is blocked by intrahippocampal interleukin-1 receptor antagonist","volume":"121","author":"Barrientos","year":"2003","journal-title":"Neuroscience"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.bbi.2022.02.019","article-title":"IL-33 in the basolateral amygdala integrates neuroinflammation into anxiogenic circuits via modulating BDNF expression","volume":"102","author":"Zhuang","year":"2022","journal-title":"Brain Behav. Immun."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1038\/s41564-018-0337-x","article-title":"The neuroactive potential of the human gut microbiota in quality of life and depression","volume":"4","author":"Falony","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.bbi.2022.02.007","article-title":"Bacteroides species differentially modulate depression-like behavior via gut-brain metabolic signaling","volume":"102","author":"Zhang","year":"2022","journal-title":"Brain Behav. Immun."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/s12974-019-1580-7","article-title":"Effect of Enterococcus faecalis 2001 on colitis and depressive-like behavior in dextran sulfate sodium-treated mice: Involvement of the brain\u2013gut axis","volume":"16","author":"Takahashi","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_147","first-page":"G989","article-title":"Modulation of the microbiota-gut-brain axis by probiotics in a murine model of inflammatory bowel disease","volume":"310","author":"Emge","year":"2016","journal-title":"Am. J. Physiol. Liver Physiol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"e108605","DOI":"10.15252\/embj.2021108605","article-title":"Commensal microbiota divergently affect myeloid subsets in the mammalian central nervous system during homeostasis and disease","volume":"40","author":"Sankowski","year":"2021","journal-title":"EMBO J."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.jnutbio.2018.08.005","article-title":"Intestinal anti-inflammatory effect of the probiotic Saccharomyces boulardii in DSS-induced colitis in mice: Impact on microRNAs expression and gut microbiota composition","volume":"61","author":"Algieri","year":"2018","journal-title":"J. Nutr. Biochem."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1016\/j.cmet.2021.10.010","article-title":"Microbiota-derived acetate enables the metabolic fitness of the brain innate immune system during health and disease","volume":"33","author":"Erny","year":"2021","journal-title":"Cell Metab."},{"key":"ref_151","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_152","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/s41593-022-01027-3","article-title":"Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N6-carboxymethyllysine","volume":"25","author":"Mossad","year":"2022","journal-title":"Nat. Neurosci."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.cell.2020.02.035","article-title":"Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism","volume":"180","author":"Duscha","year":"2020","journal-title":"Cell"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/s41586-018-0119-x","article-title":"Microglial control of astrocytes in response to microbial metabolites","volume":"557","author":"Rothhammer","year":"2018","journal-title":"Nature"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e12159","DOI":"10.1002\/jev2.12159","article-title":"Visualizing transfer of microbial biomolecules by outer membrane vesicles in microbe-host-communication in vivo","volume":"10","author":"Bittel","year":"2021","journal-title":"J. Extracell. Vesicles"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.chom.2011.04.009","article-title":"Commensal Bacteroides Species Induce Colitis in Host-Genotype-Specific Fashion in a Mouse Model of Inflammatory Bowel Disease","volume":"9","author":"Bloom","year":"2011","journal-title":"Cell Host Microbe"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Dicks, L.M.T., Hurn, D., and Hermanus, D. (2021). Gut Bacteria and Neuropsychiatric Disorders. Microorganisms, 9.","DOI":"10.3390\/microorganisms9122583"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.bbr.2017.01.021","article-title":"Effects of gut microbiota on the microRNA and mRNA expression in the hippocampus of mice","volume":"322","author":"Chen","year":"2017","journal-title":"Behav. Brain Res."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1038\/mp.2017.100","article-title":"The microbiome regulates amygdala-dependent fear recall","volume":"23","author":"Hoban","year":"2018","journal-title":"Mol. Psychiatry"},{"key":"ref_160","first-page":"992","article-title":"MicroRNA and Gut Microbiota: Tiny but Mighty\u2014Novel Insights into Their Cross-talk in Inflammatory Bowel Disease Pathogenesis and Therapeutics","volume":"16","author":"Viennois","year":"2021","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/s41586-019-1644-y","article-title":"The microbiota regulate neuronal function and fear extinction learning","volume":"574","author":"Chu","year":"2019","journal-title":"Nature"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1038\/s43587-021-00141-4","article-title":"Microbiota-dependent increase in \u03b4-valerobetaine alters neuronal function and is responsible for age-related cognitive decline","volume":"1","author":"Mossad","year":"2021","journal-title":"Nat. Aging"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s40168-021-01165-z","article-title":"Intestinal microbiota shapes gut physiology and regulates enteric neurons and glia","volume":"9","author":"Vicentini","year":"2021","journal-title":"Microbiome"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11111\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:36:53Z","timestamp":1760143013000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,21]]},"references-count":163,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911111"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911111","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,21]]}}}