Background/Aims Stress is closely related to the deterioration of digestive disease. Melatonin has potent anti-inflammatory properties. The objective of this study was to determine the effect of water stress (WS) and sleep deprivation (SD) on intestinal microbiota and roles of melatonin in stressful condition.
Methods We used C57BL/6 mice and specially designed water bath for stress and SD for 10 days. We measured melatonin concentrations in serum, feces, and colon tissues by high-performance liquid chromatography. Genomic DNA was extracted from feces and amplified using primers targeting V3 to V4 regions of bacterial 16S ribosomal RNA genes.
Results Compared to the control, melatonin concentration was lower in the WS and SD. Fecal concentration was 0.132 pg/mL in control, 0.062 pg/mL in WS, and 0.068 pg/mL in SD. In colon tissue, it was 0.45 pg/mL in control, 0.007 pg/mL in WS, and 0.03 pg/mL in SD. After melatonin treatment, melatonin concentrations in feces and colon tissue were recovered to the level of control. Metagenomic analysis of microbiota showed abundance in colitogenic microbiota in WS and SD. Melatonin injection attenuated this harmful effect. WS and SD showed decreased Lactobacillales and increased Erysipelotrichales and Enterobacteriales. Melatonin treatment increased Akkermansia muciniphila and Lactobacillus and decreased Bacteroides massiliensis and Erysipelotrichaceae.
Conclusions This study showed that stress and SD could affect intestinal dysbiosis and increase colitogenic microbiota, which could contribute to the aggravating digestive disease. Melatonin concentrations in feces and colon tissue decreased under WS and SD. Melatonin treatment brought recovery of melatonin concentration in colon tissue and modulating dysbiosis of intestinal microbiota.
Citations
Citations to this article as recorded by
Phytomelatonin: A multifunctional molecule in plant defense and metabolism Prabhjot Singh Jassal, Tarush Singh Paur, Atif Khurshid Wani Physiological and Molecular Plant Pathology.2026; 141: 102992. CrossRef
The melatonin-microbiome axis: a new frontier in gut health for the immunomodulatory, antioxidant and anti-inflammatory properties Priyanka Gupta, Biplab Debnath, Sumel Ashique, Mohhammad Ramzan, Sabina Yasmin, Eman Shorog, Shubhrajit Mantry, Mohd Tariq, Sathvik Belagodu Sridhar, Uttam Prasad Panigrahy, Himanshu Sharma, Asif Iqbal, Pranav Kumar Prabhakar, Md Yousuf Ansari Inflammopharmacology.2026; 34(1): 227. CrossRef
Bidirectional effect of intestinal microbiome and host in circadian rhythm disruption: Environmental factors and breast cancer development Evren Doruk ENGIN, Ayse Basak ENGIN, Atilla ENGIN Environmental Toxicology and Pharmacology.2026; 122: 104939. CrossRef
Advances in molecular mechanisms and therapeutic strategies for central nervous system diseases based on gut microbiota imbalance Wei Tao, Yanren Zhang, Bingbin Wang, Saiqun Nie, Li Fang, Jian Xiao, Yanqing Wu Journal of Advanced Research.2025; 69: 261. CrossRef
Sleep deprivation-induced shifts in gut microbiota: Implications for neurological disorders Nitu L. Wankhede, Mayur B. Kale, Ashishkumar Kyada, Rekha M M, Kamlesh Chaudhary, K.Satyam Naidu, Sandip Rahangdale, Prajwali V. Shende, Brijesh G. Taksande, Mohammad Khalid, Monica Gulati, Milind J. Umekar, Mohammad Fareed, Spandana Rajendra Kopalli, Sus Neuroscience.2025; 565: 99. CrossRef
Chronic Dexamethasone Disturbs the Circadian Rhythm of Melatonin and Clock Genes in Goats Liuping Cai, Qu Chen, Canfeng Hua, Liqiong Niu, Qijun Kong, Lei Wu, Yingdong Ni Animals.2025; 15(1): 115. CrossRef
Exploring the Interplay Between Gut Microbiota and the Melatonergic Pathway in Hormone Receptor-Positive Breast Cancer Aurora Laborda-Illanes, Soukaina Boutriq, Lucía Aranega-Martín, Daniel Castellano-Castillo, Lidia Sánchez-Alcoholado, Isaac Plaza-Andrades, Jesús Peralta-Linero, Emilio Alba, José Carlos Fernández-García, Alicia González-González, María Isabel Queipo-Ortu International Journal of Molecular Sciences.2025; 26(14): 6801. CrossRef
Brain-gut-microbiota interactions in sleep disorders Zhe Wang, Tingting Wu, Juan Li, Tangsheng Lu, Yifan Yu, Zichun Guan, Guohao Yuan, Zhaoyan Lv, Yiming Shan, Wei Yan, Xiaoxing Liu, Michael V. Vitiello, Qingqing Yin, Jie Sun, Lin Lu Brain Medicine.2025; : 1. CrossRef
МИКРОБИОТА КИШЕЧНИКА ПРИ НАРУШЕНИЯХ СНА В МЕНОПАУЗЕ
Н.Е. Гаращенко, Н.Е. Смурова, Н.В. Семёнова, Н.Л. Белькова, У.М. Немченко, Е.С. Клименко, Р.Е. Зугеева, С.И. Колесников, И.М. Мадаева, Л.И. Колесникова Успехи геронтологии.2025; 38(4): 562. CrossRef
The use of melatonin in the treatment of irritable bowel syndrome: a systematic review of randomized placebo-controlled clinical trials D. S. Mironov, I. A. Spirin, T. N. Trubeckaya, N. S. Shitova, V. A. Postoev Experimental and Clinical Gastroenterology.2024; (9): 168. CrossRef
Mechanism of Action of Melatonin as a Potential Adjuvant Therapy in Inflammatory Bowel Disease and Colorectal Cancer Abdo Jurjus, Jad El Masri, Maya Ghazi, Lemir Majed El Ayoubi, Lara Soueid, Alice Gerges Geagea, Rosalyn Jurjus Nutrients.2024; 16(8): 1236. CrossRef
Association between sleep disorders and constipation Risk: A systematic review and Meta-Analysis Minhui Tian, Yongfu Song, Yan Guo, Tongwei Jiang Journal of Clinical Neuroscience.2024; 126: 12. CrossRef
Melatonin and gut microbiome N. E. Garashchenko, N. V. Semenova, L. I. Kolesnikova Acta Biomedica Scientifica.2024; 9(2): 12. CrossRef
Insights into the Mechanisms of Action of Akkermansia muciniphila in the Treatment of Non-Communicable Diseases Honorata Mruk-Mazurkiewicz, Monika Kulaszyńska, Wiktoria Czarnecka, Albert Podkówka, Natalia Ekstedt, Piotr Zawodny, Anna Wierzbicka-Woś, Wojciech Marlicz, Błażej Skupin, Ewa Stachowska, Igor Łoniewski, Karolina Skonieczna-Żydecka Nutrients.2024; 16(11): 1695. CrossRef
Sleep Deprivation Induces Gut Damage via Ferroptosis Zi‐Jian Zheng, Hai‐Yi Zhang, Ya‐Lin Hu, Yan Li, Zhi‐Hong Wu, Zhi‐Peng Li, Dong‐Rui Chen, Yang Luo, Xiao‐Jing Zhang, Cang Li, Xiao‐Yu Wang, Dan Xu, Wei Qiu, Hong‐Ping Li, Xiao‐Ping Liao, Hao Ren, Jian Sun Journal of Pineal Research.2024;[Epub] CrossRef
Enhanced cerebral blood flow similarity of the somatomotor network in chronic insomnia: Transcriptomic decoding, gut microbial signatures and phenotypic roles Xiaofen Ma, Junle Li, Yuping Yang, Xiaofan Qiu, Jintao Sheng, Ningke Han, Changwen Wu, Guang Xu, Guihua Jiang, Junzhang Tian, Xuchu Weng, Jinhui Wang NeuroImage.2024; 297: 120762. CrossRef
Modifications in the Composition of the Gut Microbiota in Rats Induced by Chronic Sleep Deprivation: Potential Relation to Mental Disorders Li-Ming Zheng, Yan Li Nature and Science of Sleep.2024; Volume 16: 1313. CrossRef
Melatonin feeding changed the microbial diversity and metabolism of the broiler cecum Li Zhen, Yi Huang, Xuewen Bi, Anyu Gao, Linlin Peng, Yong Chen Frontiers in Microbiology.2024;[Epub] CrossRef
Microbial melatonin metabolism in the human intestine as a therapeutic target for dysbiosis and rhythm disorders Petra Zimmermann, Salome Kurth, Benoit Pugin, Nicholas A. Bokulich npj Biofilms and Microbiomes.2024;[Epub] CrossRef
The role of the probiotic
Akkermansia muciniphila
in brain functions: insights underpinning therapeutic potential
Ruiling Xu, Yuxuan Zhang, Shurui Chen, Yaohui Zeng, Xuan Fu, Ti Chen, Shilin Luo, Xiaojie Zhang Critical Reviews in Microbiology.2023; 49(2): 151. CrossRef
The relationship between gut microbiota and inflammatory response, learning and memory in mice by sleep deprivation Mengjie Zhang, Mengying Zhang, Guangning Kou, Yan Li Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef
Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome Brian Bicknell, Ann Liebert, Thomas Borody, Geoffrey Herkes, Craig McLachlan, Hosen Kiat International Journal of Molecular Sciences.2023; 24(11): 9577. CrossRef
Melatonin: Facts, Extrapolations and Clinical Trials J. A. Boutin, D. J. Kennaway, R. Jockers Biomolecules.2023; 13(6): 943. CrossRef
Potential of Akkermansia muciniphila and its outer membrane proteins as therapeutic targets for neuropsychological diseases Fenghua Zhang, Dali Wang Frontiers in Microbiology.2023;[Epub] CrossRef
The brain-gut-microbiota axis in the treatment of neurologic and psychiatric disorders Maria Fernanda Naufel, Giselle de Martin Truzzi, Caroline Marcantonio Ferreira, Fernando Morgadinho Santos Coelho Arquivos de Neuro-Psiquiatria.2023; 81(07): 670. CrossRef
Akkermansia muciniphila in neuropsychiatric disorders: friend or foe? Wenhui Lei, Yiwen Cheng, Jie Gao, Xia Liu, Li Shao, Qingming Kong, Nengneng Zheng, Zongxin Ling, Weiming Hu Frontiers in Cellular and Infection Microbiology.2023;[Epub] CrossRef
Targeting microbiota to alleviate the harm caused by sleep deprivation Hongyu Chen, Chen Wang, Junying Bai, Jiajia Song, Linli Bu, Ming Liang, Huayi Suo Microbiological Research.2023; 275: 127467. CrossRef
Targeting the blood–brain barrier to delay aging-accompanied neurological diseases by modulating gut microbiota, circadian rhythms, and their interplays Yanping Wang, Weihong Du, Xiaoyan Hu, Xin Yu, Chun Guo, Xinchun Jin, Wei Wang Acta Pharmaceutica Sinica B.2023;[Epub] CrossRef
The mammalian gastro‐intestinal tract is a NOT a major extra‐pineal source of melatonin David J. Kennaway Journal of Pineal Research.2023;[Epub] CrossRef
Puerarin alleviates sleep disorders in aged mice related to repairing intestinal mucosal barrier Qing Tao, Jinhua Zhang, Qiao liang, Shiyu Song, Shuxia Wang, Xiaoming Yao, Qian Gao, Lei Wang Natural Products and Bioprospecting.2023;[Epub] CrossRef
Protective and therapeutic potential of melatonin against intestinal diseases: updated review of current data based on molecular mechanisms Saeed Mehrzadi, Mohammad Sheibani, Fereshteh Koosha, Nazila Alinaghian, Mohammad Hossein Pourhanifeh, Seid Amir Pasha Tabaeian, Russel J. Reiter, Azam Hosseinzadeh Expert Review of Gastroenterology & Hepatology.2023; 17(10): 1011. CrossRef
Melatonin Ameliorates Neuropsychiatric Behaviors, Gut Microbiome, and Microbiota-Derived Metabolites in Rats with Chronic Sleep Deprivation Bingcong Li, Yin-Ru Hsieh, Wen-De Lai, Te-Hsuan Tung, Yu-Xuan Chen, Chia-Hui Yang, Yu-Chiao Fang, Shih-Yi Huang International Journal of Molecular Sciences.2023; 24(23): 16820. CrossRef
Melatonin as a Mediator of the Gut Microbiota–Host Interaction: Implications for Health and Disease María-Ángeles Bonmatí-Carrión, Maria-Angeles Rol Antioxidants.2023; 13(1): 34. CrossRef
The interplay between sleep and gut microbiota Mengqi Han, Shiying Yuan, Jiancheng Zhang Brain Research Bulletin.2022; 180: 131. CrossRef
Melatonin Mitigates Oxazolone-Induced Colitis in Microbiota-Dependent Manner Zi-xiao Zhao, Xi Yuan, Yan-yan Cui, Jun Liu, Jing Shen, Bi-ying Jin, Bing-cheng Feng, Yun-jiao Zhai, Meng-qi Zheng, Guan-jun Kou, Ru-chen Zhou, Li-xiang Li, Xiu-li Zuo, Shi-yang Li, Yan-qing Li Frontiers in Immunology.2022;[Epub] CrossRef
Human Fecal Microbiota Transplantation Reduces the Susceptibility to Dextran Sulfate Sodium-Induced Germ-Free Mouse Colitis Yapeng Yang, Xiaojiao Zheng, Yuqing Wang, Xiang Tan, Huicong Zou, Shuaifei Feng, Hang Zhang, Zeyue Zhang, Jinhui He, Bota Cui, Xueying Zhang, Zhifeng Wu, Miaomiao Dong, Wei Cheng, Shiyu Tao, Hong Wei Frontiers in Immunology.2022;[Epub] CrossRef
Circadian Rhythms and Melatonin Metabolism in Patients With Disorders of Gut-Brain Interactions Sophie Fowler, Emily C. Hoedt, Nicholas J. Talley, Simon Keely, Grace L. Burns Frontiers in Neuroscience.2022;[Epub] CrossRef
Sleep Deficiency Is Associated With Exacerbation of Symptoms and Impairment of Anorectal and Autonomic Functions in Patients With Functional Constipation Jie Liu, Wei Wang, Jiashuang Tian, Chaolan Lv, Yuhan Fu, Ronnie Fass, Gengqing Song, Yue Yu Frontiers in Neuroscience.2022;[Epub] CrossRef
The melatonergic agonist agomelatine ameliorates high fat diet-induced obesity in mice through the modulation of the gut microbiome Patricia Diez-Echave, Teresa Vezza, Francesca Algieri, Antonio Jesús Ruiz-Malagón, Laura Hidalgo-García, Federico García, Rocío Morón, Manuel Sánchez, Marta Toral, Miguel Romero, Juan Duarte, José Garrido-Mesa, María Elena Rodríguez-Cabezas, Alba Rodrígue Biomedicine & Pharmacotherapy.2022; 153: 113445. CrossRef
Melatonin protects against body weight gain induced by sleep deprivation in mice Shuang Hu, Xuan Liu, Yuefan Wang, Rong Zhang, Shougang Wei Physiology & Behavior.2022; 257: 113975. CrossRef
Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements Deanna M. Minich, Melanie Henning, Catherine Darley, Mona Fahoum, Corey B. Schuler, James Frame Nutrients.2022; 14(19): 3934. CrossRef
Intestinal microbiota and melatonin in the treatment of secondary injury and complications after spinal cord injury Yiwen Zhang, Rui Lang, Shunyu Guo, Xiaoqin Luo, Huiting Li, Cencen Liu, Wei Dong, Changshun Bao, Yang Yu Frontiers in Neuroscience.2022;[Epub] CrossRef
Melatonin–Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions Mara Ioana Iesanu, Carmen Denise Mihaela Zahiu, Ioana-Alexandra Dogaru, Diana Maria Chitimus, Gratiela Gradisteanu Pircalabioru, Suzana Elena Voiculescu, Sebastian Isac, Felicia Galos, Bogdan Pavel, Siobhain M. O’Mahony, Ana-Maria Zagrean Antioxidants.2022; 11(11): 2244. CrossRef
Altered functional connectivity strength in chronic insomnia associated with gut microbiota composition and sleep efficiency Ziwei Chen, Ying Feng, Shumei Li, Kelei Hua, Shishun Fu, Feng Chen, Huiyu Chen, Liping Pan, Caojun Wu, Guihua Jiang Frontiers in Psychiatry.2022;[Epub] CrossRef
Melatonin Is Neuroprotective in Escherichia coli Meningitis Depending on Intestinal Microbiota Dong Zhang, Shu Xu, Hucong Wu, Jiaqi Liu, Yiting Wang, Guoqiang Zhu International Journal of Molecular Sciences.2022; 24(1): 298. CrossRef
Melatonin and Cancer: A Polyhedral Network Where the Source Matters Maria-Angeles Bonmati-Carrion, Antonia Tomas-Loba Antioxidants.2021; 10(2): 210. CrossRef
Changes in gut microbiota composition and their associations with cortisol, melatonin and interleukin 6 in patients with chronic insomnia AA Masyutina, LN Gumenyuk, YuV Fatovenko, LE Sorokina, SS Bayramova, AI Alekseenko, YuV Shavrov, AA Romanova, DI Seydametova Bulletin of Russian State Medical University.2021;[Epub] CrossRef
Microbiota Modulates Cardiac Transcriptional Responses to Intermittent Hypoxia and Hypercapnia Dan Zhou, Jin Xue, Yukiko Miyamoto, Orit Poulsen, Lars Eckmann, Gabriel G. Haddad Frontiers in Physiology.2021;[Epub] CrossRef