{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:00:12Z","timestamp":1792684812756,"version":"4.5.0"},"reference-count":67,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Growing evidence indicates that the gut microbiota is not a static ecosystem but a rhythmic metabolic organ whose oscillatory activity is tightly coordinated with host circadian biology. Disruption of this temporal alignment, through irregular diet, sleep disturbance, shift work, or social jet lag, may profoundly alter microbial composition and the production of neuroactive metabolites. These alterations have emerged as potential contributors to the pathophysiology of mood disorders. This review introduces the concept of chrono-metabolic psychiatry, a framework integrating circadian rhythms, gut microbiota dynamics, and host metabolic signaling in the development and course of depressive and bipolar disorders. In this framework, the term \u201cchrono-metabolic\u201d refers to the integration of biological timing, host metabolic regulation, and microbiota-derived metabolic signaling. Chrono-metabolic psychiatry therefore shifts the focus from static dysbiosis or neurotransmitter imbalance alone to the time-dependent interactions among circadian misalignment, microbial rhythmicity, immune regulation, metabolite production, and affective instability. Diurnal fluctuations in short-chain fatty acids, tryptophan\u2013kynurenine metabolites, bile acids, and microbial-derived neurotransmitters interact with clock gene regulation, hypothalamic\u2013pituitary\u2013adrenal axis activity, neuroinflammation, and synaptic plasticity. Chrono-disruption may represent a transdiagnostic vulnerability factor and may confirm the bidirectional relationship between mood instability and microbiota rhythmicity. Emerging therapeutic implications, including chrono-nutrition, time-restricted feeding, targeted probiotic administration (\u201cchronobiotics\u201d), and the microbiota-modulating effects of psychotropic medications are discussed. By shifting from a compositional to a temporal\u2013metabolic perspective, this model highlights the importance of microbial oscillations rather than static dysbiosis alone. Integrating circadian biology into microbiota research may enable metabolomic stratification and pave the way for precision psychiatry approaches grounded in host\u2013microbe metabolic crosstalk. Future longitudinal and time-resolved multi-omics studies are needed to validate this framework and to translate it into clinically actionable interventions.<\/jats:p>","DOI":"10.3390\/metabo16060400","type":"journal-article","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T09:46:54Z","timestamp":1780998414000},"page":"400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A Chrono-Metabolic Approach to Mental Health: Current Perspectives on Circadian Rhythms, Gut Microbiota, and Microbial Metabolites in Mood Disorders"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7058-4927","authenticated-orcid":false,"given":"Giuseppe","family":"Marano","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Head-Neck and Chest, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Neuroscience, Section of Psychiatry, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8861-794X","authenticated-orcid":false,"given":"Mariateresa","family":"Acanfora","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Head-Neck and Chest, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Neuroscience, Section of Psychiatry, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5286-1878","authenticated-orcid":false,"given":"Luca","family":"Conci","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Head-Neck and Chest, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Neuroscience, Section of Psychiatry, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6558-2932","authenticated-orcid":false,"given":"Gianandrea","family":"Traversi","sequence":"additional","affiliation":[{"name":"Unit of Medical Genetics, Department of Laboratory Medicine, Ospedale Isola Tiberina-Gemelli Isola, 00186 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osvaldo","family":"Mazza","sequence":"additional","affiliation":[{"name":"Spine Surgery Department, Bambino Ges\u00f9 Children\u2019s Hospital IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esmeralda","family":"Capristo","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Gaetani","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Unit of Internal Medicine, Cristo Re Hospital, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2950-3395","authenticated-orcid":false,"given":"Gianluca","family":"Franceschini","sequence":"additional","affiliation":[{"name":"Breast Surgery Unit, Department of Woman and Child\u2019s Health and Public Health Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Medical and Surgical Sciences, Catholic University of the Sacred Heart, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3007-8162","authenticated-orcid":false,"given":"Marianna","family":"Mazza","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Head-Neck and Chest, Section of Psychiatry, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Neuroscience, Section of Psychiatry, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Grau-Del Valle, C., Fern\u00e1ndez, J., Sol\u00e1, E., Montoya-Castilla, I., Morillas, C., and Ba\u00f1uls, C. (2023). Association between gut microbiota and psychiatric disorders: A systematic review. Front. Psychol., 14.","DOI":"10.3389\/fpsyg.2023.1215674"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"6076","DOI":"10.2174\/1381612822666160914183804","article-title":"The Gut Microbiota and the Emergence of Autoimmunity: Relevance to Major Psychiatric Disorders","volume":"22","author":"Severance","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"105990","DOI":"10.1016\/j.neubiorev.2024.105990","article-title":"Vagus nerve stimulation and gut microbiota interactions: A novel therapeutic avenue for neuropsychiatric disorders","volume":"169","author":"Faraji","year":"2025","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Marano, G., Mazza, M., Lisci, F.M., Ciliberto, M., Traversi, G., Kotzalidis, G.D., De Berardis, D., Laterza, L., Sani, G., and Gasbarrini, A. (2023). The Microbiota\u2013Gut\u2013Brain Axis: Psychoneuroimmunological Insights. Nutrients, 15.","DOI":"10.3390\/nu15061496"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Francis, T.C., and Porcu, A. (2023). Emotionally clocked out: Cell-type specific regulation of mood and anxiety by the circadian clock system in the brain. Front. Mol. Neurosci., 16.","DOI":"10.3389\/fnmol.2023.1188184"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/nrg.2016.150","article-title":"Transcriptional architecture of the mammalian circadian clock","volume":"18","author":"Takahashi","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Anafi, R.C., Lee, Y., Sato, T.K., Venkataraman, A., Ramanathan, C., Kavakli, I.H., Hughes, M.E., Baggs, J.E., Growe, J., and Liu, A.C. (2014). Machine learning helps identify CHRONO as a circadian clock component. PLoS Biol., 12.","DOI":"10.1371\/journal.pbio.1001840"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/ejn.14253","article-title":"Mood-related central and peripheral clocks","volume":"51","author":"Ketchesin","year":"2020","journal-title":"Eur. J. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"10892","DOI":"10.1038\/s41598-017-11297-8","article-title":"The circadian clock in immune cells controls the magnitude of Leishmania parasite infection","volume":"7","author":"Kiessling","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1080\/07420528.2017.1278704","article-title":"Owls, larks, swifts, woodcocks and they are not alone: A historical review of methodology for multidimensional self-assessment of individual differences in sleep-wake pattern","volume":"34","author":"Putilov","year":"2017","journal-title":"Chronobiol. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1111\/ejn.14255","article-title":"Circadian disruption: What do we actually mean?","volume":"51","author":"Vetter","year":"2020","journal-title":"Eur. J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1080\/07420528.2019.1684937","article-title":"Evening chronotype, late weekend sleep times and social jetlag as possible causes of sleep curtailment after maintaining perennial DST: Ain\u2019t they as black as they are painted?","volume":"37","author":"Putilov","year":"2020","journal-title":"Chronobiol. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1126\/science.aad2958","article-title":"CIRCADIAN RHYTHMS. Caffeine, the circadian clock, and sleep","volume":"349","author":"Landolt","year":"2015","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1177\/0748730412456367","article-title":"Cellular Circadian Clocks in Mood Disorders","volume":"27","author":"McCarthy","year":"2012","journal-title":"J. Biol. Rhythm."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Astiz, M., Heyde, I., and Oster, H. (2019). Mechanisms of Communication in the Mammalian Circadian Timing System. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20020343"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/mp.2013.12","article-title":"An important role for cholecystokinin, a CLOCK target gene, in the development and treatment of manic-like behaviors","volume":"19","author":"Arey","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1007\/s11920-015-0637-2","article-title":"Circadian Clocks as Modulators of Metabolic Comorbidity in Psychiatric Disorders","volume":"17","author":"Barandas","year":"2015","journal-title":"Curr. Psychiatry Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.copsyc.2019.09.002","article-title":"Chronotype, circadian rhythms and mood","volume":"34","author":"Bauducco","year":"2020","journal-title":"Curr. Opin. Psychol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1080\/07420528.2019.1636813","article-title":"Associations between social jetlag and mental health in young people: A systematic review","volume":"36","author":"Henderson","year":"2019","journal-title":"Chronobiol. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17m11565","DOI":"10.4088\/JCP.17m11565","article-title":"Circadian Rhythm Sleep-Wake Disorders Predict Shorter Time to Relapse of Mood Episodes in Euthymic Patients with Bipolar Disorder: A Prospective 48-Week Study","volume":"79","author":"Takaesu","year":"2018","journal-title":"J. Clin. Psychiatry"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Smith, R.P., Easson, C., Lyle, S.M., Kapoor, R., Donnelly, C.P., Davidson, E.J., Parikh, E., Lopez, J.V., and Tartar, J.L. (2019). Gut microbiome diversity is associated with sleep physiology in humans. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0222394"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.cell.2014.09.048","article-title":"Transkingdom Control of Microbiota Diurnal Oscillations Promotes Metabolic Homeostasis","volume":"159","author":"Thaiss","year":"2014","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.chom.2015.03.006","article-title":"Effects of Diurnal Variation of Gut Microbes and High-Fat Feeding on Host Circadian Clock Function and Metabolism","volume":"17","author":"Leone","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1080\/09168451.2018.1444467","article-title":"Flavonoid metabolism: The interaction of metabolites and gut microbiota","volume":"82","author":"Murota","year":"2018","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1097\/SPC.0000000000000498","article-title":"Does circadian rhythm influence gastrointestinal toxicity?","volume":"14","author":"Hofmeister","year":"2020","journal-title":"Curr. Opin. Support. Palliat. Care"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Summa, K.C., Voigt, R.M., Forsyth, C.B., Shaikh, M., Cavanaugh, K., Tang, Y., Vitaterna, M.H., Song, S., Turek, F.W., and Keshavarzian, A. (2013). Disruption of the Circadian Clock in Mice Increases Intestinal Permeability and Promotes Alcohol-Induced Hepatic Pathology and Inflammation. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0067102"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"35405","DOI":"10.1038\/srep35405","article-title":"Chronic Sleep Disruption Alters Gut Microbiota, Induces Systemic and Adipose Tissue Inflammation and Insulin Resistance in Mice","volume":"6","author":"Poroyko","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1016\/j.cell.2016.05.041","article-title":"From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites","volume":"165","author":"Koh","year":"2016","journal-title":"Cell"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1194\/jlr.R036012","article-title":"The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism","volume":"54","author":"Groen","year":"2013","journal-title":"J. Lipid Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.1038\/s41598-018-19836-7","article-title":"Gut Microbiota-Derived Short Chain Fatty Acids Induce Circadian Clock Entrainment in Mouse Peripheral Tissue","volume":"8","author":"Tahara","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"dos Santos, A., and Vasylyshyn, A. (2025). The modulatory role of short-chain fatty acids on peripheral circadian gene expression: A systematic review. Front. Physiol., 16.","DOI":"10.3389\/fphys.2025.1595057"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1186\/s12944-024-02203-z","article-title":"Effects of short-chain fatty acid-butyrate supplementation on expression of circadian-clock genes, sleep quality, and inflammation in patients with active ulcerative colitis: A double-blind randomized controlled trial","volume":"23","author":"Firoozi","year":"2024","journal-title":"Lipids Health Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.neuropharm.2015.11.015","article-title":"Tryptophan availability for kynurenine pathway metabolism across the life span: Control mechanisms and focus on aging, exercise, diet and nutritional supplements","volume":"112","author":"Badawy","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Luki\u0107, I., Getselter, D., Koren, O., and Elliott, E. (2019). Role of Tryptophan in Microbiota-Induced Depressive-Like Behavior: Evidence From Tryptophan Depletion Study. Front. Behav. Neurosci., 13.","DOI":"10.3389\/fnbeh.2019.00123"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4265","DOI":"10.1038\/s41380-020-0645-4","article-title":"An integrated meta-analysis of peripheral blood metabolites and biological functions in major depressive disorder","volume":"26","author":"Pu","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10014","DOI":"10.1038\/s41467-024-53673-9","article-title":"Exposing 24-hour cycles in bile acids of male humans","volume":"15","author":"Bello","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Xing, C., Huang, X., Zhang, Y., Zhang, C., Wang, W., Wu, L., Ding, M., Zhang, M., and Song, L. (2020). Sleep Disturbance Induces Increased Cholesterol Level by NR1D1 Mediated CYP7A1 Inhibition. Front. Genet., 11.","DOI":"10.3389\/fgene.2020.610496"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.atherosclerosis.2020.08.015","article-title":"Shift work, and particularly permanent night shifts, promote dyslipidaemia: A systematic review and meta-analysis","volume":"313","author":"Dutheil","year":"2020","journal-title":"Atherosclerosis"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Albrecht, U. (2017). Molecular Mechanisms in Mood Regulation Involving the Circadian Clock. Front. Neurol., 8.","DOI":"10.3389\/fneur.2017.00030"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/s42003-022-03468-9","article-title":"Short-chain fatty acids promote the effect of environmental signals on the gut microbiome and metabolome in mice","volume":"5","author":"Marrocco","year":"2022","journal-title":"Commun. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/clpt.2011.296","article-title":"The roles of neurotrophic factor and Wnt signaling in depression","volume":"91","author":"Voleti","year":"2012","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/sj.mp.4002097","article-title":"Repeated social defeat-induced depression-like behavioral and biological alterations in rats: Involvement of cholecystokinin","volume":"13","author":"Becker","year":"2008","journal-title":"Mol. Psychiatry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/nrn3229","article-title":"Impaired mitochondrial function in psychiatric disorders","volume":"13","author":"Manji","year":"2012","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1101\/sqb.2011.76.010520","article-title":"The time of metabolism: NAD+, SIRT1, and the circadian clock","volume":"76","author":"Bellet","year":"2011","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1007\/s00018-023-04834-4","article-title":"Effect of early vs. late time-restricted high-fat feeding on circadian metabolism and weight loss in obese mice","volume":"80","author":"Tsameret","year":"2023","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"166749","DOI":"10.1016\/j.bbadis.2023.166749","article-title":"Effect of time-restricted feeding on high-fat diet-induced metabolic dysfunction in Drosophila melanogaster\u201d","volume":"1869","author":"Quenti","year":"2023","journal-title":"Biochim. Et Biophys. Acta Mol. Basis Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"556","DOI":"10.21037\/atm.2019.09.64","article-title":"Time-restricted feeding during childhood has persistent effects on mice commensal microbiota","volume":"7","author":"Hu","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1159\/000538781","article-title":"PROVIT-CLOCK: A Potential Influence of Probiotics and Vitamin B7 Add-On Treatment and Metabolites on Clock Gene Expression in Major Depression","volume":"83","author":"Kreuzer","year":"2024","journal-title":"Neuropsychobiology"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ho, Y., Tsai, Y., Kuo, T., and Yang, C. (2021). Effects of Lactobacillus plantarum PS128 on Depressive Symptoms and Sleep Quality in Self-Reported Insomniacs: A Randomized, Double-Blind, Placebo-Controlled Pilot Trial. Nutrients, 13.","DOI":"10.3390\/nu13082820"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Lan, Y., Lu, J., Qiao, G., Mao, X., Zhao, J., Wang, G., Tian, P., and Chen, W. (2023). Bifidobacterium breve CCFM1025 Improves Sleep Quality via Regulating the Activity of the HPA Axis: A Randomized Clinical Trial. Nutrients, 15.","DOI":"10.3390\/nu15214700"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3722","DOI":"10.7150\/ijms.115387","article-title":"The probiotic Lactobacillus kefiranofaciens K6 alleviates exercise and sleep deprivation-induced physiological dysregulation and neuropsychiatric disorders via modulation of inflammation, circadian rhythm, and stress response","volume":"22","author":"Chen","year":"2025","journal-title":"Int. J. Med. Sci."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Gao, K., Chen, C., Zheng, Z., Fan, Q., Wang, H., Li, Y., and Chen, S. (2024). Lactococcus strains with psychobiotic properties improve cognitive and mood alterations in aged mice. Front. Nutr., 11.","DOI":"10.3389\/fnut.2024.1439094"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1039\/D5FO02921J","article-title":"Bifidobacterium longum supplementation prevents intestinal inflammation and cognitive impairment in sleep-deprived mice by modulating clock gene expression","volume":"17","author":"Huang","year":"2025","journal-title":"Food Funct."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/phar.1890","article-title":"Interaction Between Atypical Antipsychotics and the Gut Microbiome in a Bipolar Disease Cohort","volume":"37","author":"Flowers","year":"2017","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/ijnp\/pyaa070","article-title":"Effects of Psychotropics on the Microbiome in Patients with Depression and Anxiety: Considerations in a Naturalistic Clinical Setting","volume":"24","author":"Tomizawa","year":"2020","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2545","DOI":"10.1038\/s41380-024-02857-2","article-title":"Medication use is associated with distinct microbial features in anxiety and depression","volume":"30","author":"Dilmore","year":"2025","journal-title":"Mol. Psychiatry"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41398-024-03208-z","article-title":"The role of gut microbiota and metabolomic pathways in modulating the efficacy of SSRIs for major depressive disorder","volume":"14","author":"Jiang","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41398-024-03211-4","article-title":"Gut microbiota dysbiosis promotes cognitive impairment via bile acid metabolism in major depressive disorder","volume":"14","author":"Jia","year":"2024","journal-title":"Transl. Psychiatry"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/bdi.12682","article-title":"A step ahead: Exploring the gut microbiota in inpatients with bipolar disorder during a depressive episode","volume":"21","author":"Painold","year":"2018","journal-title":"Bipolar Disord."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Stolfi, F., Abreu, H., Sinella, R., Nembrini, S., Centonze, S., Landra, V., Brasso, C., Cappellano, G., Rocca, P., and Chiocchetti, A. (2024). Omics approaches open new horizons in major depressive disorder: From biomarkers to precision medicine. Front. Psychiatry, 15.","DOI":"10.3389\/fpsyt.2024.1422939"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"115605","DOI":"10.1016\/j.psychres.2023.115605","article-title":"Metabolome subtyping reveals multi-omics characteristics and biological heterogeneity in major psychiatric disorders","volume":"330","author":"Hao","year":"2023","journal-title":"Psychiatry Res."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Ma, S., Nie, Z., Zhang, M., Mei, J., Zhou, E., Hu, Z., Lv, H., Gong, Q., Wang, G., and Wang, H. (2025). Towards precision psychiatry: Metabolomics identifies three biological subtypes of depression. PLoS Digit. Health, 4.","DOI":"10.1371\/journal.pdig.0001125"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1001\/jamapsychiatry.2023.4096","article-title":"Metabolomic Biomarker Signatures for Bipolar and Unipolar Depression","volume":"81","author":"Tomasik","year":"2023","journal-title":"JAMA Psychiatry"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/s41398-018-0183-x","article-title":"Diagnosis of major depressive disorder based on changes in multiple plasma neurotransmitters: A targeted metabolomics study","volume":"8","author":"Pan","year":"2018","journal-title":"Transl. Psychiatry"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jad.2024.03.114","article-title":"Evaluation of metabolomics-based urinary biomarker models for recognizing major depression disorder and bipolar disorder","volume":"356","author":"Wang","year":"2024","journal-title":"J. Affect. Disord."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Marano, G., Rossi, S., Sfratta, G., Traversi, G., Lisci, F.M., Anesini, M.B., Pola, R., Gasbarrini, A., Gaetani, E., and Mazza, M. (2025). Gut Microbiota: A New Challenge in Mood Disorder Research. 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