{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T18:55:42Z","timestamp":1784832942436,"version":"3.55.0"},"reference-count":68,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University\u2013Industry Cooperation Fund, National Taiwan Sport University, Taoyuan, Taiwan","award":["1131054"],"award-info":[{"award-number":["1131054"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Insomnia is prevalent and difficult to treat safely over the long term. Given the role of the microbiota\u2013gut\u2013brain axis in melatonin and hypothalamic\u2013pituitary\u2013adrenal (HPA) regulation, and preclinical evidence for Limosilactobacillus fermentum PS150, we evaluated whether a heat-treated formulation (HT-PS150) could improve sleep and modulate endocrine\/circadian markers in adults with poor sleep. Methods: In a randomized, double-blind, placebo-controlled trial, 84 adults aged 20\u201360 years with PSQI \u2265 5 and ISI &lt; 22 were assigned to receive either placebo or HT-PS150 for eight weeks. Outcomes included patient-reported sleep (PSQI, ISI), anxiety\/depression (GAD-7, PHQ-9), quality of life (QLESQ-SF), gastrointestinal symptoms (VAS-GI), wrist actigraphy (Fitbit Inspire 3), and sleep-relevant biomarkers measured from urine, saliva, and\/or blood samples (melatonin, cortisol, orexin, serotonin, GABA, and\/or norepinephrine). Repeated measures were analyzed using generalized estimating equations. An exploratory proportional regulation analysis classified individual biomarker changes as up- or down-regulated and compared proportions between study arms. Per-protocol analyses required \u226580% compliance. Results: Improvements in the primary outcomes, PSQI and ISI, were observed over time in both groups, while no significant group \u00d7 time interactions were detected. In exploratory proportional analyses, a higher proportion of participants in the HT-PS150 group exhibited up-regulated nocturnal melatonin secretion and improved daytime plasma orexin levels, as well as a tendency toward greater reductions in nocturnal salivary cortisol compared with placebo. In subgroup analyses with higher baseline insomnia severity (ISI \u2265 8), HT-PS150 was associated with greater improvements in PSQI (notably sleep duration and efficiency) and reduction in anxiety (GAD-7) upon post hoc testing. Conclusions: Although group mean scores on sleep symptom scales did not differ significantly in the full cohort, HT-PS150 appeared to modulate sleep\u2013wake regulation by enhancing nocturnal melatonin secretion, attenuating HPA-axis activity, and stabilizing wakefulness. Clinical benefits were most evident among participants with greater baseline symptom burden, suggesting potential utility in more symptomatic populations.<\/jats:p>","DOI":"10.3390\/nu18010014","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T14:27:16Z","timestamp":1766154436000},"page":"14","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Heat-Treated Limosilactobacillus fermentum PS150 Improves Sleep Quality with Severity-Dependent Benefits: A Randomized, Placebo-Controlled Trial"],"prefix":"10.3390","volume":"18","author":[{"given":"Mon-Chien","family":"Lee","sequence":"first","affiliation":[{"name":"Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan City 333325, Taiwan"},{"name":"Center for General Education, Taipei Medical University, Taipei 110301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan City 333325, Taiwan"},{"name":"Physical Education Office, National Taipei University of Business, Taipei 100025, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Yun","family":"Chen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan City 333325, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1446-6787","authenticated-orcid":false,"given":"Chi-Chang","family":"Huang","sequence":"additional","affiliation":[{"name":"Graduate Institute of Sports Science, National Taiwan Sport University, Taoyuan City 333325, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"119679","DOI":"10.1016\/j.jad.2025.119679","article-title":"From quality of life to sleep quality in Chinese college students: Stress and anxiety as sequential mediators with nonlinear effects via machine learning","volume":"389","author":"Zang","year":"2025","journal-title":"J. Affect. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s13340-016-0279-6","article-title":"Metabolic disturbances: Role of the circadian timing system and sleep","volume":"8","author":"Adhikary","year":"2017","journal-title":"Diabetol. Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2147\/NSS.S18891","article-title":"Impact of lifestyle and technology developments on sleep","volume":"4","author":"Shochat","year":"2012","journal-title":"Nat. Sci. Sleep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e70089","DOI":"10.1111\/jsr.70089","article-title":"The Prevalence of Insomnia Disorder in the General Population: A Meta-Analysis","volume":"34","author":"Weinreich","year":"2025","journal-title":"J. Sleep Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"151","DOI":"10.2147\/NSS.S134864","article-title":"Short- and long-term health consequences of sleep disruption","volume":"9","author":"Medic","year":"2017","journal-title":"Nat. Sci. Sleep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"307","DOI":"10.5664\/jcsm.6470","article-title":"Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline","volume":"13","author":"Sateia","year":"2017","journal-title":"J. Clin. Sleep Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Labad, J., Salvat-Pujol, N., Armario, A., Cabezas, A., Arriba-Arnau, A., Nadal, R., Martorell, L., Urretavizcaya, M., Monreal, J.A., and Crespo, J.M. (2020). The Role of Sleep Quality, Trait Anxiety and Hypothalamic-Pituitary-Adrenal Axis Measures in Cognitive Abilities of Healthy Individuals. Int. J. Environ. Res. Public. Health, 17.","DOI":"10.3390\/ijerph17207600"},{"key":"ref_8","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_9","doi-asserted-by":"crossref","unstructured":"Berm\u00fadez-Humar\u00e1n, L.G., Salinas, E., Ortiz, G.G., Ramirez-Jirano, L.J., Morales, J.A., and Bitzer-Quintero, O.K. (2019). From Probiotics to Psychobiotics: Live Beneficial Bacteria Which Act on the Brain-Gut Axis. Nutrients, 11.","DOI":"10.3390\/nu11040890"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Khalil, M., Di Ciaula, A., Mahdi, L., Jaber, N., Di Palo, D.M., Graziani, A., Baffy, G., and Portincasa, P. (2024). Unraveling the Role of the Human Gut Microbiome in Health and Diseases. Microorganisms, 12.","DOI":"10.3390\/microorganisms12112333"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e37114","DOI":"10.1097\/MD.0000000000037114","article-title":"The correlation between gut microbiota and both neurotransmitters and mental disorders: A narrative review","volume":"103","author":"Mhanna","year":"2024","journal-title":"Medicine"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104527","DOI":"10.1016\/j.ebiom.2023.104527","article-title":"Gut microbiota and its metabolites in depression: From pathogenesis to treatment","volume":"90","author":"Liu","year":"2023","journal-title":"eBioMedicine"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Xiong, R.-G., Li, J., Cheng, J., Zhou, D.-D., Wu, S.-X., Huang, S.-Y., Saimaiti, A., Yang, Z.-J., Gan, R.-Y., and Li, H.-B. (2023). The Role of Gut Microbiota in Anxiety, Depression, and Other Mental Disorders as Well as the Protective Effects of Dietary Components. Nutrients, 15.","DOI":"10.3390\/nu15143258"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Cao, Y., Cheng, Y., Pan, W., Diao, J., Sun, L., and Meng, M. (2025). Gut microbiota variations in depression and anxiety: A systematic review. BMC Psychiatry, 25.","DOI":"10.1186\/s12888-025-06871-8"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Silva, Y.P., Bernardi, A., and Frozza, R.L. (2020). The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00025"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"20220910","DOI":"10.1515\/biol-2022-0910","article-title":"Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects","volume":"19","author":"Lin","year":"2024","journal-title":"Open Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sun, J., Fang, D., Wang, Z., and Liu, Y. (2023). Sleep Deprivation and Gut Microbiota Dysbiosis: Current Understandings and Implications. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119603"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/nrgastro.2014.66","article-title":"Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic","volume":"11","author":"Hill","year":"2014","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.1007\/s12031-022-02053-3","article-title":"Psychobiotics: The Influence of Gut Microbiota on the Gut-Brain Axis in Neurological Disorders","volume":"72","author":"Oroojzadeh","year":"2022","journal-title":"J. Mol. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.jfda.2019.01.002","article-title":"Psychobiotics in mental health, neurodegenerative and neurodevelopmental disorders","volume":"27","author":"Cheng","year":"2019","journal-title":"J. Food Drug Anal."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Del Toro-Barbosa, M., Hurtado-Romero, A., Garcia-Amezquita, L.E., and Garcia-Cayuela, T. (2020). Psychobiotics: Mechanisms of Action, Evaluation Methods and Effectiveness in Applications with Food Products. Nutrients, 12.","DOI":"10.3390\/nu12123896"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"153","DOI":"10.3920\/BM2016.0150","article-title":"Beneficial effects of Lactobacillus casei strain Shirota on academic stress-induced sleep disturbance in healthy adults: A double-blind, randomised, placebo-controlled trial","volume":"8","author":"Takada","year":"2017","journal-title":"Benef. Microbes"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.jff.2017.01.042","article-title":"Daily intake of Lactobacillus gasseri CP2305 improves mental, physical, and sleep quality among Japanese medical students enrolled in a cadaver dissection course","volume":"31","author":"Sawada","year":"2017","journal-title":"J. Funct. Foods"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/j.clnesp.2024.07.006","article-title":"Effects of probiotics on sleep parameters: A systematic review and meta-analysis","volume":"63","author":"Ito","year":"2024","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Liu, Y., Yu, Y., Lu, S., Tan, K., Jiang, P., Liu, P., and Peng, Q. (2025). Impact of probiotics on sleep quality and mood states in patients with insomnia: A systematic review and meta-analysis. Front. Microbiol., 16.","DOI":"10.3389\/fmicb.2025.1596990"},{"key":"ref_26","first-page":"e80810","article-title":"The Bidirectional Relationship Between the Gut Microbiome and Mental Health: A Comprehensive Review","volume":"17","author":"Rathore","year":"2025","journal-title":"Cureus"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Zhu, R., Fang, Y., Li, H., Liu, Y., Wei, J., Zhang, S., Wang, L., Fan, R., Wang, L., and Li, S. (2023). Psychobiotic Lactobacillus plantarum JYLP-326 relieves anxiety, depression, and insomnia symptoms in test anxious college via modulating the gut microbiota and its metabolism. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1158137"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Tanihiro, R., Yuki, M., Sasai, M., Haseda, A., Kagami-Katsuyama, H., Hirota, T., Honma, N., and Nishihira, J. (2024). Effects of Prebiotic Yeast Mannan on Gut Health and Sleep Quality in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Study. Nutrients, 16.","DOI":"10.3390\/nu16010141"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ji, H.F., Li, M., Han, X., Fan, Y.T., Yang, J.J., Long, Y., Yu, J., and Ji, H.Y. (2025). Lactobacilli-Mediated Regulation of the Microbial-Immune Axis: A Review of Key Mechanisms, Influencing Factors, and Application Prospects. Foods, 14.","DOI":"10.3390\/foods14101763"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Pique, N., Berlanga, M., and Minana-Galbis, D. (2019). Health Benefits of Heat-Killed (Tyndallized) Probiotics: An Overview. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102534"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2374","DOI":"10.1039\/C5FO01396H","article-title":"Heat-killed and live Lactobacillus reuteri GMNL-263 exhibit similar effects on improving metabolic functions in high-fat diet-induced obese rats","volume":"7","author":"Hsieh","year":"2016","journal-title":"Food Funct."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Lin, A., Shih, C.-T., Huang, C.-L., Wu, C.-C., Lin, C.-T., and Tsai, Y.-C. (2019). Hypnotic Effects of Lactobacillus fermentum PS150TM on Pentobarbital-Induced Sleep in Mice. Nutrients, 11.","DOI":"10.3390\/nu11102409"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"16313","DOI":"10.1038\/s41598-021-95659-3","article-title":"Lactobacillus fermentum PS150 promotes non-rapid eye movement sleep in the first night effect of mice","volume":"11","author":"Lin","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0165-1781(89)90047-4","article-title":"The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research","volume":"28","author":"Buysse","year":"1989","journal-title":"Psychiatry Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1007\/s11136-005-4346-x","article-title":"Psychometric evaluation of the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI) in primary insomnia and control subjects","volume":"14","author":"Tsai","year":"2005","journal-title":"Qual. Life Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S1389-9457(00)00065-4","article-title":"Validation of the Insomnia Severity Index as an outcome measure for insomnia research","volume":"2","author":"Bastien","year":"2001","journal-title":"Sleep. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1093\/sleep\/34.5.601","article-title":"The Insomnia Severity Index: Psychometric indicators to detect insomnia cases and evaluate treatment response","volume":"34","author":"Morin","year":"2011","journal-title":"Sleep."},{"key":"ref_38","first-page":"95","article-title":"Reliability and validity of the Chinese version of insomnia severity index","volume":"4","author":"Yang","year":"2009","journal-title":"Arch. Clin. Psychol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1001\/archinte.166.10.1092","article-title":"A brief measure for assessing generalized anxiety disorder: The GAD-7","volume":"166","author":"Spitzer","year":"2006","journal-title":"Arch. Intern. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1046\/j.1525-1497.2001.016009606.x","article-title":"The PHQ-9: Validity of a brief depression severity measure","volume":"16","author":"Kroenke","year":"2001","journal-title":"J. Gen. Intern. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.comppsych.2010.04.013","article-title":"Validation of Patient Health Questionnaire for depression screening among primary care patients in Taiwan","volume":"52","author":"Liu","year":"2011","journal-title":"Compr. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1007\/s11136-013-0528-0","article-title":"Validity and reliability of the Chinese version of the Short Form of Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-SF)","volume":"23","author":"Lee","year":"2014","journal-title":"Qual. Life Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/j.1365-2850.2011.01735.x","article-title":"Quality of Life Enjoyment and Satisfaction Questionnaire\u2013short form for quality of life assessments in clinical practice: A psychometric study","volume":"18","author":"Stevanovic","year":"2011","journal-title":"J. Psychiatr. Ment. Health Nurs."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nutres.2007.10.001","article-title":"Probiotic food supplement reduces stress-induced gastrointestinal symptoms in volunteers: A double-blind, placebo-controlled, randomized trial","volume":"28","author":"Diop","year":"2008","journal-title":"Nutr. Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Wu, S.-I., Wu, C.-C., Tsai, P.-J., Cheng, L.-H., Hsu, C.-C., Shan, I.-K., Chan, P.-Y., Lin, T.-W., Ko, C.-J., and Chen, W.-L. (2021). Psychobiotic supplementation of PS128TM improves stress, anxiety, and insomnia in highly stressed information technology specialists: A pilot study. Front. Nutr., 8.","DOI":"10.3389\/fnut.2021.614105"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Bengtsson, M., Ohlsson, B., and Ulander, K. (2007). Development and psychometric testing of the Visual Analogue Scale for Irritable Bowel Syndrome (VAS-IBS). BMC Gastroenterol., 7.","DOI":"10.1186\/1471-230X-7-16"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jmpt.2003.11.003","article-title":"Assessing the clinical significance of change scores recorded on subjective outcome measures","volume":"27","author":"Hurst","year":"2004","journal-title":"J. Manip. Physiol. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1080\/07420528.2019.1682006","article-title":"Performance assessment of new-generation Fitbit technology in deriving sleep parameters and stages","volume":"37","author":"Haghayegh","year":"2020","journal-title":"Chronobiol. Int."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e16273","DOI":"10.2196\/16273","article-title":"Accuracy of wristband Fitbit models in assessing sleep: Systematic review and meta-analysis","volume":"21","author":"Haghayegh","year":"2019","journal-title":"J. Med. Internet Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"59","DOI":"10.2147\/NSS.S391802","article-title":"Validation of Fitbit Inspire 2TM Against Polysomnography in Adults Considering Adaptation for Use","volume":"15","author":"Lim","year":"2023","journal-title":"Nat. Sci. Sleep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e12710","DOI":"10.1111\/jsr.12710","article-title":"The impact of stress on sleep: Pathogenic sleep reactivity as a vulnerability to insomnia and circadian disorders","volume":"27","author":"Kalmbach","year":"2018","journal-title":"J. Sleep Res."},{"key":"ref_52","first-page":"e84232","article-title":"The Role of Sleep and the Effects of Sleep Loss on Cognitive, Affective, and Behavioral Processes","volume":"17","author":"Hyndych","year":"2025","journal-title":"Cureus"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1177\/074873049701200507","article-title":"Salivary Melatonin as a Circadian Phase Marker: Validation and Comparison to Plasma Melatonin","volume":"12","author":"Voultsios","year":"1997","journal-title":"J. Biol. Rhythm."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"66","DOI":"10.5664\/jcsm.27083","article-title":"Measuring Melatonin in Humans","volume":"4","author":"Benloucif","year":"2008","journal-title":"J. Clin. Sleep Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e12961","DOI":"10.1111\/jpi.12961","article-title":"Melatonin in energy control: Circadian time-giver and homeostatic monitor","volume":"76","author":"Challet","year":"2024","journal-title":"J. Pineal Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1210\/jc.2004-1056","article-title":"On the interactions of the hypothalamic-pituitary-adrenal (HPA) axis and sleep: Normal HPA axis activity and circadian rhythm, exemplary sleep disorders","volume":"90","author":"Buckley","year":"2005","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.neures.2017.03.015","article-title":"The roles of orexins in sleep\/wake regulation","volume":"118","author":"Mieda","year":"2017","journal-title":"Neurosci. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0306-4530(02)00123-3","article-title":"Serum melatonin and urinary 6-sulfatoxymelatonin in major depression","volume":"29","author":"Crasson","year":"2004","journal-title":"Psychoneuroendocrinology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"zsae087","DOI":"10.1093\/sleep\/zsae087","article-title":"Daily associations between salivary cortisol and electroencephalographic-assessed sleep: A 15-day intensive longitudinal study","volume":"47","author":"Yap","year":"2024","journal-title":"Sleep"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"M\u00e4kel\u00e4, K.A., Karhu, T., Jurado Acosta, A., Vakkuri, O., Lepp\u00e4luoto, J., and Herzig, K.-H. (2018). Plasma Orexin-A Levels Do Not Undergo Circadian Rhythm in Young Healthy Male Subjects. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00710"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Teame, T., Wang, A., Xie, M., Zhang, Z., Yang, Y., Ding, Q., Gao, C., Olsen, R.E., Ran, C., and Zhou, Z. (2020). Paraprobiotics and Postbiotics of Probiotic Lactobacilli, Their Positive Effects on the Host and Action Mechanisms: A Review. Front. Nutr., 7.","DOI":"10.3389\/fnut.2020.570344"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e12498","DOI":"10.1111\/jpi.12498","article-title":"Melatonin promotes sleep in mice by inhibiting orexin neurons in the perifornical lateral hypothalamus","volume":"65","author":"Sharma","year":"2018","journal-title":"J. Pineal Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1080\/23328940.2022.2109932","article-title":"Sleep disruption induces activation of inflammation and heightens risk for infectious disease: Role of impairments in thermoregulation and elevated ambient temperature","volume":"10","author":"Irwin","year":"2023","journal-title":"Temperature"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1536","DOI":"10.1038\/s41430-020-0656-x","article-title":"Effects of probiotics and paraprobiotics on subjective and objective sleep metrics: A systematic review and meta-analysis","volume":"74","author":"Irwin","year":"2020","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Yu, B., Wang, K.Y., Wang, N.R., Zhang, L., and Zhang, J.P. (2024). Effect of probiotics and paraprobiotics on patients with sleep disorders and sub-healthy sleep conditions: A meta-analysis of randomized controlled trials. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1477533"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1007\/s00259-010-1663-2","article-title":"Measuring serotonin synthesis: From conventional methods to PET tracers and their (pre)clinical implications","volume":"38","author":"Visser","year":"2011","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Milbank, E., and Lopez, M. (2019). Orexins\/Hypocretins: Key Regulators of Energy Homeostasis. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00830"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Huang, C.-L., Chu, H.-F., Wu, C.-C., Deng, F.-S., Wen, P.-J., Chien, S.-P., Chao, C.-H., Chen, Y.-T., Lu, M.-K., and Tsai, Y.-C. (2023). Exopolysaccharide is the potential effector of Lactobacillus fermentum PS150, a hypnotic psychobiotic strain. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1209067"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/1\/14\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T14:30:56Z","timestamp":1766154656000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/1\/14"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,19]]},"references-count":68,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["nu18010014"],"URL":"https:\/\/doi.org\/10.3390\/nu18010014","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,19]]}}}