{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:14:58Z","timestamp":1788430498014,"version":"build-2803163510"},"reference-count":130,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5P20GM152333-02"],"award-info":[{"award-number":["5P20GM152333-02"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"award":["5P20GM152333-02"],"award-info":[{"award-number":["5P20GM152333-02"]}],"id":[{"id":"https:\/\/ror.org\/045p44t13","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Adolescence represents a pivotal, yet understudied, developmental window in which maturation of the gut microbiome, neural circuits, endocrine systems, and behavioral processes converge. Although early-life microbiota\u2013gut\u2013brain interactions are well established, emerging evidence demonstrates that adolescence constitutes a \u201csecond sensitive period\u201d during which microbial composition, metabolic output, and immune function undergo substantial restructuring. These microbial transitions parallel key neurodevelopmental events, including synaptic pruning, dopaminergic refinement, and heightened neuroendocrine activity, suggesting a coordinated microbiome\u2013gut\u2013brain developmental program. Cross-species comparisons reveal broad alignment between rodent and human adolescent milestones, though inconsistencies in development staging present challenges for translational interpretation. Environmental influences\u2014such as diet, stress, antibiotics, and physical activity\u2014further modulate microbial and neural maturation during this period, with potential long-term consequences for cognition, emotion, and stress responsivity. Mechanistically, microbial metabolites, vagal pathways, immune mediators, and steroid hormone interactions constitute key interfaces linking the gut microbiome to adolescent brain function. Recognizing adolescence as a mechanistically rich and plastic phase of gut\u2013brain co-development underscores the need for harmonized methodological approaches and developmental alignment frameworks. Methods-Results: This review synthesizes ontogenetic, mechanistic, and translational evidence to highlight conserved microbiome\u2013gut\u2013brain pathways and identifies opportunities for targeted interventions during this critical developmental stage.<\/jats:p>","DOI":"10.3390\/nu18172891","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:20:43Z","timestamp":1788427243000},"page":"2891","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Adolescent Microbiome\u2013Gut\u2013Brain Axis: Development, Mechanisms, and Translational Perspectives"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4786-3287","authenticated-orcid":false,"given":"Dolores B.","family":"Vazquez-Sanroman","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, Oklahoma State University Center for Health Sciences, 1111 W. 17 Street, Tulsa, OK 74107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Longaberger","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Oklahoma State University Center for Health Sciences, 1111 W. 17 Street, Tulsa, OK 74107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alondra","family":"Chance","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Oklahoma State University Center for Health Sciences, 1111 W. 17 Street, Tulsa, OK 74107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1903-5735","authenticated-orcid":false,"given":"Michael","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Oklahoma State University Center for Health Sciences, 1111 W. 17 Street, Tulsa, OK 74107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7500-8996","authenticated-orcid":false,"given":"Nedra","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Oklahoma State University Center for Health Sciences, 1111 W. 17 Street, Tulsa, OK 74107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerwald","family":"Koehler","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Oklahoma State University Center for Health Sciences, 1111 W. 17 Street, Tulsa, OK 74107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The microbiota\u2013gut\u2013brain axis","volume":"99","author":"Cryan","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.biopsych.2023.10.006","article-title":"Adolescence, the Microbiota-Gut-Brain Axis, and the Emergence of Psychiatric Disorders","volume":"95","author":"Ahn","year":"2024","journal-title":"Biol. Psychiatry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.bbi.2022.12.008","article-title":"Critical Windows of Early-Life Microbiota Disruption on Behaviour, Neuroimmune Function, and Neurodevelopment","volume":"108","author":"Lynch","year":"2023","journal-title":"Brain Behav. Immun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e01294-23","DOI":"10.1128\/msystems.01294-23","article-title":"Taxonomic and Metabolic Development of the Human Gut Microbiome across Life Stages: A Worldwide Metagenomic Investigation","volume":"9","author":"Mancabelli","year":"2024","journal-title":"mSystems"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1053\/j.gastro.2020.08.065","article-title":"Childhood Development and the Microbiome\u2014The Intestinal Microbiota in Maintenance of Health and Development of Disease During Childhood Development","volume":"160","author":"Ronan","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13041-023-01020-2","article-title":"Behavioral phenotype, intestinal microbiome, and brain neuronal activity of male serotonin transporter knockout mice","volume":"16","author":"Shoji","year":"2023","journal-title":"Mol. Brain"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Huo, R., Zeng, B., Zeng, L., Cheng, K., Li, B., Luo, Y., Wang, H., Zhou, C., Fang, L., and Li, W. (2017). Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis. Front. Cell. Infect. Microbiol., 7.","DOI":"10.3389\/fcimb.2017.00489"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/dev.21821","article-title":"Is adolescence the missing developmental link in Microbiome-Gut-Brain axis communication?","volume":"61","author":"Flannery","year":"2019","journal-title":"Dev. Psychobiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.jcmgh.2018.04.003","article-title":"The Brain-Gut-Microbiome Axis","volume":"6","author":"Martin","year":"2018","journal-title":"Cell Mol. Gastroenterol. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Dash, S., Syed, Y.A., and Khan, M.R. (2022). Understanding the Role of the Gut Microbiome in Brain Development and Its Association with Neurodevelopmental Psychiatric Disorders. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.880544"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pneurobio.2013.04.001","article-title":"Brain Development in Rodents and Humans: Identifying Benchmarks of Maturation and Vulnerability to Injury across Species","volume":"106","author":"Semple","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.tics.2015.07.008","article-title":"Adolescence as a Sensitive Period of Brain Development","volume":"19","author":"Fuhrmann","year":"2015","journal-title":"Trends Cogn. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2654","DOI":"10.1111\/ejn.13291","article-title":"Adult microbiota-deficient mice have distinct dendritic morphological changes: Differential effects in the amygdala and hippocampus","volume":"44","author":"Luczynski","year":"2016","journal-title":"Eur. J. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3002","DOI":"10.1038\/s41380-023-02071-6","article-title":"Gut microbiota changes require vagus nerve integrity to promote depressive-like behaviors in mice","volume":"28","author":"Siopi","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1016\/j.celrep.2016.04.074","article-title":"Ly6C(hi) Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis","volume":"15","author":"Mattei","year":"2016","journal-title":"Cell Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4124","DOI":"10.1038\/s41380-023-02229-2","article-title":"Acute and Long-Term Effects of Adolescence Stress Exposure on Rodent Adult Hippocampal Neurogenesis, Cognition, and Behaviour","volume":"28","author":"Borsini","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Esposito, P., and Ismail, N. (2022). Linking Puberty and the Gut Microbiome to the Pathogenesis of Neurodegenerative Disorders. Microorganisms, 10.","DOI":"10.3390\/microorganisms10112163"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.yfrne.2005.10.003","article-title":"Pubertal hormones organize the adolescent brain and behavior","volume":"26","author":"Sisk","year":"2005","journal-title":"Front. Neuroendocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/cdep.12429","article-title":"The Pubertal Stress Recalibration Hypothesis: Potential Neural and Behavioral Consequences","volume":"15","author":"DePasquale","year":"2021","journal-title":"Child Dev. Perspect."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/s40168-018-0587-0","article-title":"Estrogen-Mediated Gut Microbiome Alterations Influence Sexual Dimorphism in Metabolic Syndrome in Mice","volume":"6","author":"Kaliannan","year":"2018","journal-title":"Microbiome"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Elderman, M., De Vos, P., and Faas, M. (2018). Role of Microbiota in Sexually Dimorphic Immunity. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.01018"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1037\/bne0000584","article-title":"Impact of Supplementation with Omega-3 Fatty Acids after Maternal Dietary Deficiency on Adolescent Anxiety and Microglial Morphology","volume":"138","author":"Bogachuk","year":"2024","journal-title":"Behav. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1016\/j.ajpath.2023.07.004","article-title":"Adolescence and the Microbiome","volume":"193","author":"Carson","year":"2023","journal-title":"Am. J. Pathol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Zhu, Z., Cheng, Y., Liu, X., Xu, X., Ding, W., Ling, Z., Liu, J., and Cai, G. (2025). The Microbiota-Gut-Brain Axis in Depression: Unraveling the Relationships and Therapeutic Opportunities. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1644160"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Dey, P. (2025). Genes, guts, and microbes: Decoding host-driven microbial regulation using intestine-specific conditional knockouts. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1674913"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Petrut, S.M., Bragaru, A.M., Munteanu, A.E., Moldovan, A.D., Moldovan, C.A., and Rusu, E. (2025). Gut over Mind: Exploring the Powerful Gut-Brain Axis. Nutrients, 17.","DOI":"10.3390\/nu17050842"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"23","DOI":"10.20517\/mrr.2022.11","article-title":"The Gut-Immune-Brain Axis in Neurodevelopment and Neurological Disorders","volume":"1","author":"Park","year":"2022","journal-title":"Microbiome Res. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6213","DOI":"10.2147\/JIR.S384949","article-title":"Vagus Nerve and Underlying Impact on the Gut Microbiota-Brain Axis in Behavior and Neurodegenerative Diseases","volume":"15","author":"Han","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Suganya, K., and Koo, B.S. (2020). Gut-Brain Axis: Role of Gut Microbiota on Neurological Disorders and How Probiotics\/Prebiotics Beneficially Modulate Microbial and Immune Pathways to Improve Brain Functions. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21207551"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"G541","DOI":"10.1152\/ajpgi.00288.2020","article-title":"Early Life Interaction between the Microbiota and the Enteric Nervous System","volume":"319","author":"Foong","year":"2020","journal-title":"Am. J. Physiol.-Gastrointest. Liver Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/978-1-4939-0897-4_5","article-title":"Vagal pathways for microbiome-brain-gut axis communication","volume":"817","author":"Forsythe","year":"2014","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Bonaz, B., Bazin, T., and Pellissier, S. (2018). The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00049"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1007\/s00401-023-02629-2","article-title":"Microglial contribution to the pathology of neurodevelopmental disorders in humans","volume":"146","author":"Matuleviciute","year":"2023","journal-title":"Acta Neuropathol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mavrych, V., Mansour, G.K., Hajjar, A.W., and Bolgova, O. (2025). Hormonal and Behavioral Consequences of Social Isolation and Loneliness: Neuroendocrine Mechanisms and Clinical Implications. Int. J. Mol. Sci., 27.","DOI":"10.20944\/preprints202511.1132.v1"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1002\/dev.21187","article-title":"Vagal regulation and internalizing psychopathology among adolescents exposed to childhood adversity","volume":"56","author":"McLaughlin","year":"2014","journal-title":"Dev. Psychobiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1038\/s41579-023-00933-y","article-title":"Antibiotic perturbations to the gut microbiome","volume":"21","author":"Fishbein","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"106728","DOI":"10.1016\/j.neubiorev.2026.106728","article-title":"Experience-dependent development of vagal circuitry in rodents and humans","volume":"187","author":"Panvini","year":"2026","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Van Dyken, P., and Lacoste, B. (2018). Impact of Metabolic Syndrome on Neuroinflammation and the Blood-Brain Barrier. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00930"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/s42003-026-09737-1","article-title":"Antibiotic-induced gut microbiome remodeling reduces neuroinflammation in traumatic brain injury","volume":"9","author":"Flinn","year":"2026","journal-title":"Commun. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"103293","DOI":"10.1016\/j.ebiom.2021.103293","article-title":"Short chain fatty acids and its producing organisms: An overlooked therapy for IBD?","volume":"66","author":"Deleu","year":"2021","journal-title":"eBioMedicine"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zhang, R., Ding, N., Feng, X., and Liao, W. (2025). The gut microbiome, immune modulation, and cognitive decline: Insights on the gut-brain axis. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1529958"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.neubiorev.2016.05.035","article-title":"Immunoadolescence: Neuroimmune development and adolescent behavior","volume":"70","author":"Brenhouse","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"agad055","DOI":"10.1093\/alcalc\/agad055","article-title":"The Adolescent and Young Adult Microbiome and Its Association with Substance Use: A Scoping Review","volume":"59","author":"Browning","year":"2024","journal-title":"Alcohol Alcohol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1196\/annals.1440.010","article-title":"The Adolescent Brain","volume":"1124","author":"Casey","year":"2008","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"153951","DOI":"10.1016\/j.metabol.2019.153951","article-title":"Neuroinflammation disorders exacerbated by environmental stressors","volume":"100","author":"Miller","year":"2019","journal-title":"Metabolism"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1113\/jphysiol.2004.063388","article-title":"Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice","volume":"558","author":"Sudo","year":"2004","journal-title":"J. Physiol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Guevara-Ram\u00edrez, P., Tamayo-Trujillo, R., Ruiz-Pozo, V.A., Cadena-Ullauri, S., Paz-Cruz, E., and Zambrano, A.K. (2025). Mechanistic Links Between Gut Dysbiosis, Insulin Resistance, and Autism Spectrum Disorder. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26136537"},{"key":"ref_48","first-page":"214","article-title":"Reframing the teenage wasteland: Adolescent microbiota\u2013gut\u2013brain axis","volume":"25","author":"Neufeld","year":"2016","journal-title":"J. Can. Acad. Child Adolesc. Psychiatry"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/j.2040-4603.2016.tb00694.x","article-title":"Regulation of the Hypothalamic-Pituitary-Adrenocortical Stress Response","volume":"6","author":"Herman","year":"2016","journal-title":"Compr. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Bertollo, A.G., Santos, C.F., Bagatini, M.D., and Ign\u00e1cio, Z.M. (2025). Hypothalamus-pituitary-adrenal and gut-brain axes in biological interaction pathway of the depression. Front. Neurosci., 19.","DOI":"10.3389\/fnins.2025.1541075"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"987","DOI":"10.4081\/cp.2017.987","article-title":"Gut microbiota\u2019s effect on mental health: The gut-brain axis","volume":"7","author":"Clapp","year":"2017","journal-title":"Clin. Pract."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Fusco, W., Lorenzo, M.B., Cintoni, M., Porcari, S., Rinninella, E., Kaitsas, F., Lener, E., Mele, M.C., Gasbarrini, A., and Collado, M.C. (2023). Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota. Nutrients, 15.","DOI":"10.3390\/nu15092211"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e101374","DOI":"10.1136\/gpsych-2023-101374","article-title":"Gut microbiota-derived short-chain fatty acids and depression: Deep insight into biological mechanisms and potential applications","volume":"37","author":"Cheng","year":"2024","journal-title":"Gen. Psychiatry"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Visekruna, A., and Luu, M. (2021). The Role of Short-Chain Fatty Acids and Bile Acids in Intestinal and Liver Function, Inflammation, and Carcinogenesis. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.703218"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/s41583-020-00381-0","article-title":"Gut microbial molecules in behavioural and neurodegenerative conditions","volume":"21","author":"Needham","year":"2020","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Luo, W., Li, R., Pan, C., and Luo, C. (2025). Gut microbiota-derived metabolites in immunomodulation and gastrointestinal cancer immunotherapy. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1710880"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3930","DOI":"10.1016\/j.neuron.2021.09.036","article-title":"Microbiota\u2013brain interactions: Moving toward mechanisms in model organisms","volume":"109","author":"Nagpal","year":"2021","journal-title":"Neuron"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"bqae098","DOI":"10.1210\/endocr\/bqae098","article-title":"Changes in the Bile Acid Pool and Timing of Female Puberty: Potential Novel Role of Hypothalamic TGR5","volume":"165","author":"Vandeputte","year":"2024","journal-title":"Endocrinology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1101\/sqb.2018.83.037457","article-title":"Nucleus Accumbens Modulation in Reward and Aversion","volume":"83","author":"Klawonn","year":"2018","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2644677","DOI":"10.1080\/19490976.2026.2644677","article-title":"Gut microbiome and metabolic health: Mechanisms and precision interventions","volume":"18","author":"Li","year":"2026","journal-title":"Gut Microbes"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e02075-24","DOI":"10.1128\/mbio.02075-24","article-title":"From Microbes to Mind: Germ-Free Models in Neuropsychiatric Research","volume":"15","author":"Cuesta","year":"2024","journal-title":"mBio"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1073\/pnas.1010529108","article-title":"Normal gut microbiota modulates brain development and behavior","volume":"108","author":"Wang","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"110895","DOI":"10.1016\/j.isci.2024.110895","article-title":"Microbiota-Dependent Early-Life Programming of Gastrointestinal Motility","volume":"27","author":"Frith","year":"2024","journal-title":"iScience"},{"key":"ref_64","first-page":"3649","article-title":"Fecal Microbiota Transplantation from Young-Trained Donors Improves Cognitive Function in Old Mice Through Modulation of the Gut-Brain Axis","volume":"16","author":"Cerna","year":"2024","journal-title":"Aging Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"599\u2013609, 609.e1-3","DOI":"10.1053\/j.gastro.2011.04.052","article-title":"The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice","volume":"141","author":"Bercik","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut microbiota regulation of tryptophan metabolism in health and disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2989","DOI":"10.1113\/jphysiol.2014.273995","article-title":"The microbiota-gut-brain axis in gastrointestinal disorders: Stressed bugs, stressed brain or both?","volume":"592","author":"Collins","year":"2014","journal-title":"J. Physiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.tics.2018.04.006","article-title":"The Microbiome in Psychology and Cognitive Neuroscience","volume":"22","author":"Sarkar","year":"2018","journal-title":"Trends Cogn. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Hamamah, S., Aghazarian, A., Nazaryan, A., Hajnal, A., and Covasa, M. (2022). Role of Microbiota-Gut-Brain Axis in Regulating Dopaminergic Signaling. Biomedicines, 10.","DOI":"10.3390\/biomedicines10020436"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Barbu, A.C., Stoleru, S., Zugravu, A., Poenaru, E., Dragomir, A., Costescu, M., Aurelian, S.M., Shhab, Y., Stoleru, C.M., and Coman, O.A. (2025). Dopamine and the Gut Microbiota: Interactions Within the Microbiota-Gut-Brain Axis and Therapeutic Perspectives. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27010271"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Morais, J., Marques, C., Faria, A., Teixeira, D., Barreiros-Mota, I., Dur\u00e3o, C., Ara\u00fajo, J., Ismael, S., Brito, S., and Cardoso, M. (2021). Influence of Human Milk on Very Preterms\u2019 Gut Microbiota and Alkaline Phosphatase Activity. Nutrients, 13.","DOI":"10.3390\/nu13051564"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.psyneuen.2014.01.014","article-title":"Absence of the gut microbiota enhances anxiety-like behavior and neuroendocrine response to acute stress in rats","volume":"42","author":"Jaglin","year":"2014","journal-title":"Psychoneuroendocrinology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e00261-19","DOI":"10.1128\/mSystems.00261-19","article-title":"Age- and Sex-Dependent Patterns of Gut Microbial Diversity in Human Adults","volume":"4","author":"Kelley","year":"2019","journal-title":"mSystems"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Beurel, E., and Nemeroff, C.B. (2024). Early Life Adversity, Microbiome, and Inflammatory Responses. Biomolecules, 14.","DOI":"10.3390\/biom14070802"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1159\/000544950","article-title":"Microbiome and Brain Development: A Tale of Two Systems","volume":"81","author":"Cryan","year":"2025","journal-title":"Ann. Nutr. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"100541","DOI":"10.1016\/j.bbih.2022.100541","article-title":"The gut microbiota, HPA axis, and brain in adolescent-onset depression: Probiotics as a novel treatment","volume":"26","author":"Freimer","year":"2022","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1002\/bmc.2912","article-title":"Quantification of conjugated metabolites of drugs in biological matrices after the hydrolysis with \u03b2-glucuronidase and sufatase: A review of bio-analytical methods","volume":"27","author":"Ding","year":"2013","journal-title":"BioMed Chromatogr."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.medici.2017.03.002","article-title":"Plasticity of vagal afferent signaling in the gut","volume":"53","author":"Grabauskas","year":"2017","journal-title":"Medicina"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.4103\/NRR.NRR-D-24-01127","article-title":"Synaptic pruning mechanisms and application of emerging imaging techniques in neurological disorders","volume":"21","author":"Xing","year":"2026","journal-title":"Neural Regen. Res."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.biopsych.2010.04.004","article-title":"Hypothalamic-pituitary-adrenal axis dysregulation in dysphoric children and adolescents: Cortisol reactivity to psychosocial stress from preschool through middle adolescence","volume":"68","author":"Hankin","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/jcpp.12784","article-title":"Annual Research Review: Early Adversity, the Hypothalamic\u2013Pituitary\u2013Adrenocortical Axis, and Child Psychopathology","volume":"59","author":"Koss","year":"2018","journal-title":"J. Child Psychol. Psychiatry"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Swann, J.R., Spitzer, S.O., and Heijtz, R.D. (2020). Developmental Signatures of Microbiota-Derived Metabolites in the Mouse Brain. Metabolites, 10.","DOI":"10.3390\/metabo10050172"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.neubiorev.2018.09.005","article-title":"Adolescence as a neurobiological critical period for the development of higher-order cognition","volume":"94","author":"Larsen","year":"2018","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Varghese, S., Rao, S., Khattak, A., Zamir, F., and Chaari, A. (2024). Physical Exercise and the Gut Microbiome: A Bidirectional Relationship Influencing Health and Performance. Nutrients, 16.","DOI":"10.3390\/nu16213663"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1080\/10408444.2024.2362985","article-title":"Dietary glycation compounds\u2014Implications for human health","volume":"54","author":"Hellwig","year":"2024","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2387936","DOI":"10.1080\/29933935.2024.2387936","article-title":"Microbial ecology and metabolism of emerging adulthood: Gut microbiome insights from a college freshman cohort","volume":"1","author":"Mohr","year":"2024","journal-title":"Gut Microbes Rep."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"22941","DOI":"10.1038\/s41598-021-02231-0","article-title":"Gut microbiota depletion from early adolescence alters anxiety and depression-related behaviours in male mice with Alzheimer-like disease","volume":"11","author":"Mosaferi","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2125739","DOI":"10.1080\/19490976.2022.2125739","article-title":"Regulation of Microglial Physiology by the Microbiota","volume":"14","author":"Cook","year":"2022","journal-title":"Gut Microbes"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/s41398-022-01922-0","article-title":"Role of Diet and Its Effects on the Gut Microbiome in the Pathophysiology of Mental Disorders","volume":"12","author":"Horn","year":"2022","journal-title":"Transl. Psychiatry"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1897212","DOI":"10.1080\/19490976.2021.1897212","article-title":"The role of short-chain fatty acids in the interplay between gut microbiota and diet in cardio-metabolic health","volume":"13","author":"Nogal","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"486","DOI":"10.5056\/jnm20079","article-title":"Effects of a Psychobiotic Supplement on Serum Brain-Derived Neurotrophic Factor Levels in Depressive Patients: A Post Hoc Analysis of a Randomized Clinical Trial","volume":"26","author":"Kazemi","year":"2020","journal-title":"J. Neurogastroenterol. Motil."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Kumar, A., Pramanik, J., Goyal, N., Chauhan, D., Sivamaruthi, B.S., Prajapati, B.G., and Chaiyasut, C. (2023). Gut Microbiota in Anxiety and Depression: Unveiling the Relationships and Management Options. Pharmaceuticals, 16.","DOI":"10.3390\/ph16040565"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Warren, A., Nyavor, Y., Beguelin, A., and Frame, L.A. (2024). Dangers of the Chronic Stress Response in the Context of the Microbiota-Gut-Immune-Brain Axis and Mental Health: A Narrative Review. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1365871"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Maniangat Luke, A., Kumari, N.S., Hegde, M.N., and Hegde, N.N. (2025). Metabolic interplay of SCFA\u2019s in the gut and oral microbiome: A link to health and disease. Front. Oral Health, 6.","DOI":"10.3389\/froh.2025.1646382"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"390","DOI":"10.3390\/microbiolres14010030","article-title":"How do diet patterns, single foods, prebiotics and probiotics impact gut microbiota?","volume":"14","author":"Piccioni","year":"2023","journal-title":"Microbiol. Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1097\/MED.0000000000000614","article-title":"Chemosensing in enteroendocrine cells: Mechanisms and therapeutic opportunities","volume":"28","author":"Yang","year":"2021","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Schlatterer, K., Peschel, A., and Kretschmer, D. (2021). Short-Chain Fatty Acid and FFAR2 Activation\u2014A New Option for Treating Infections?. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.785833"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/s41575-019-0157-3","article-title":"The role of short-chain fatty acids in microbiota\u2013gut\u2013brain communication","volume":"16","author":"Dalile","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/s41575-026-01203-x","article-title":"The critical role of gut-brain signalling in eating behaviour and obesity","volume":"23","author":"Brierley","year":"2026","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"35455","DOI":"10.1038\/srep35455","article-title":"Alterations of the Host Microbiome Affect Behavioral Responses to Cocaine","volume":"6","author":"Kiraly","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Marano, G., Sfratta, G., Marzo, E.M., Cozzo, G., Abate, F., Traversi, G., Mazza, O., Capristo, E., Gaetani, E., and Mazza, M. (2025). The Pediatric Microbiota-Gut-Brain Axis: Implications for Neuropsychiatric Development and Intervention. Children, 12.","DOI":"10.3390\/children12111561"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41522-024-00477-w","article-title":"The gut microbiota modulate locomotion via vagus-dependent glucagon-like peptide-1 signaling","volume":"10","author":"Lai","year":"2024","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2649448","DOI":"10.1080\/19490976.2026.2649448","article-title":"From gut dysbiosis to eubiosis: Understanding microbiome recovery as an ecological process","volume":"18","author":"Kennedy","year":"2026","journal-title":"Gut Microbes"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/mp.2016.44","article-title":"Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host\u2019s metabolism","volume":"21","author":"Zheng","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/s41398-020-01073-0","article-title":"Enduring neurobehavioral effects induced by microbiota depletion during the adolescent period","volume":"10","author":"Lach","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Anand, N., Gorantla, V.R., and Chidambaram, S.B. (2022). The Role of Gut Dysbiosis in the Pathophysiology of Neuropsychiatric Disorders. Cells, 12.","DOI":"10.3390\/cells12010054"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1186\/s12967-025-07279-4","article-title":"Harnessing the microbiota-gut-brain axis to prevent and treat pediatric neurodevelopmental disorders: Translational insights and strategies","volume":"23","author":"Alkuwaiti","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Aguilera, M., G\u00e1lvez-Ontiveros, Y., and Rivas, A. (2020). Endobolome, a New Concept for Determining the Influence of Microbiota Disrupting Chemicals (MDC) in Relation to Specific Endocrine Pathogenesis. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.578007"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s40168-015-0101-x","article-title":"Structure and Function of the Healthy Pre-Adolescent Pediatric Gut Microbiome","volume":"3","author":"Hollister","year":"2015","journal-title":"Microbiome"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Laue, H.E., Coker, M.O., and Madan, J.C. (2022). The developing microbiome from birth to 3 years: The gut\u2013brain axis and neurodevelopmental outcomes. Front. Pediatr., 10.","DOI":"10.3389\/fped.2022.815885"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"4455","DOI":"10.1007\/s00213-015-4072-1","article-title":"Cocaine-induced plasticity in the cerebellum of sensitized mice","volume":"232","author":"Leto","year":"2015","journal-title":"Psychopharmacology"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"99996","DOI":"10.5498\/wjp.v15.i2.99996","article-title":"Cumulative effects of stress-sensitivity factors on depressive symptoms and suicide risk: A prospective study","volume":"15","author":"Qin","year":"2025","journal-title":"World J. Psychiatry"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1016\/j.cell.2012.01.035","article-title":"The Impact of the Gut Microbiota on Human Health: An Integrative View","volume":"148","author":"Clemente","year":"2012","journal-title":"Cell"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1038\/s41598-023-28862-z","article-title":"Longitudinal profiles of the fecal metabolome during the first two years of life","volume":"13","author":"Holzhausen","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_115","first-page":"282","article-title":"Maternal gut bacteria promote neurodevelopment through microbial metabolites","volume":"586","author":"Kim","year":"2020","journal-title":"Nature"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1017\/S0007114523002271","article-title":"Associations between dietary habits, socio-demographics and gut microbial composition in adolescents","volume":"131","author":"Kemp","year":"2023","journal-title":"Br. J. Nutr."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.neubiorev.2018.06.004","article-title":"Puberty and the human brain: Insights into adolescent development","volume":"92","author":"Vijayakumar","year":"2018","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"549","DOI":"10.4168\/aair.2022.14.5.549","article-title":"Bifidobacterium longum and Galactooligosaccharide Improve Skin Barrier Dysfunction and Atopic Dermatitis-like Skin","volume":"14","author":"Kim","year":"2022","journal-title":"Allergy Asthma Immunol. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1111\/j.1574-6941.2011.01120.x","article-title":"Distal gut microbiota of adolescent children is different from that of adults","volume":"77","author":"Agans","year":"2011","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41522-025-00861-0","article-title":"The testobolome in microbial testosterone metabolism and human health","volume":"12","author":"Veerus","year":"2026","journal-title":"npj Biofilms Microbiomes"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"e1174","DOI":"10.1212\/WNL.0000000000010149","article-title":"Patterns of motor recovery and structural neuroplasticity after basal ganglia infarcts","volume":"95","author":"Liu","year":"2020","journal-title":"Neurology"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"20150122","DOI":"10.1098\/rstb.2015.0122","article-title":"Sex differences in the gut microbiome-brain axis across the lifespan","volume":"371","author":"Morrison","year":"2016","journal-title":"Philos. Trans. R Soc. Lond. B Biol. Sci."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"111174","DOI":"10.1016\/j.mce.2021.111174","article-title":"Gut feelings about bacterial steroid-17,20-desmolase","volume":"525","author":"Ly","year":"2021","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Kaltsas, A., Giannakodimos, I., Markou, E., Stavropoulos, M., Deligiannis, D., Kratiras, Z., and Chrisofos, M. (2025). The Androbactome and the Gut Microbiota\u2013Testis Axis: A Narrative Review of Emerging Insights into Male Fertility. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26136211"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Alemany, M. (2022). The Roles of Androgens in Humans: Biology, Metabolic Regulation and Health. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911952"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/s41467-025-56498-2","article-title":"Plant-nanoparticles enhance anti-PD-L1 efficacy by shaping human commensal microbiota metabolites","volume":"16","author":"Teng","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s12944-022-01702-1","article-title":"Replacing saturated fatty acids with polyunsaturated fatty acids increases the abundance of Lachnospiraceae and is associated with reduced total cholesterol levels\u2014A randomized controlled trial in healthy individuals","volume":"21","author":"Gaundal","year":"2022","journal-title":"Lipids Health Dis."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1093\/ajcn\/84.6.1308","article-title":"Effects of n\u20133 long-chain polyunsaturated fatty acids on depressed mood: Systematic review of published trials","volume":"84","author":"Appleton","year":"2006","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.bbr.2014.07.027","article-title":"Serotonin, tryptophan metabolism and the brain-gut-microbiome axis","volume":"277","author":"Clarke","year":"2015","journal-title":"Behav. Brain Res."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s00281-018-0716-7","article-title":"The microgenderome revealed: Sex differences in bidirectional interactions between the microbiota, hormones, immunity and disease susceptibility","volume":"41","author":"Vemuri","year":"2019","journal-title":"Semin. Immunopathol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/17\/2891\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:26:10Z","timestamp":1788427570000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/17\/2891"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":130,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["nu18172891"],"URL":"https:\/\/doi.org\/10.3390\/nu18172891","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}