Intestinal diseases caused by physiological stress have become
a severe public health threat worldwide. Disturbances in the
gut microbiota-host relationship have been associated with
irritable bowel disease (IBD), while melatonin (MT) has antiinflammatory
and antioxidant effects. The objective of this
study was to investigate the mechanisms by which MT-mediated
protection mitigated stress-induced intestinal microbiota
dysbiosis and inflammation. We successfully established a
murine restraint stress model with and without MT supplementation.
Mice subjected to restraint stress had significantly
elevated corticosterone (CORT) levels, decreased MT levels
in their plasma, elevated colonic ROS levels and increased bacterial
abundance, including Bacteroides and Tyzzerella, in
their colon tract, which led to elevated expression of Toll-like
receptor (TLR) 2/4, p-P65 and p-IκB. In contrast, supplementation
with 20 mg/kg MT reversed the elevation of the plasma
CORT levels, downregulated the colon ROS levels and inhibited
the changes in the intestinal microbiota induced by
restraint stress. These effects, in turn, inhibited the activities
of TLR2 and TLR4, p-P65 and p-IκB, and decreased the inflammatory
reaction induced by restraint stress. Our results
suggested that MT may mitigate “restraint stress”-induced
colonic microbiota dysbiosis and intestinal inflammation by
inhibiting the activation of the NF-κB pathway.
Citations
Citations to this article as recorded by
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
Toll-like receptor 4 plays a vital role in irritable bowel syndrome: a scoping review Xuemeng Wan, Liyuan Wang, Zhiling Wang, Chaomin Wan Frontiers in Immunology.2024;[Epub] CrossRef
Christensenella minuta mitigates behavioral and cardiometabolic hallmarks of social defeat stress A. Agusti, GV. Molina-Mendoza, M. Tamayo, V. Rossini, MC. Cenit, C. Frances-Cuesta, V. Tolosa-Enguis, EM. Gómez Del Pulgar, A. Flor-Duro, Y. Sanz Biomedicine & Pharmacotherapy.2024; 180: 117377. CrossRef
The impact of acute and chronic stress on gastrointestinal physiology and function: a microbiota–gut–brain axis perspective Sarah‐Jane Leigh, Friederike Uhlig, Lars Wilmes, Paula Sanchez‐Diaz, Cassandra E. Gheorghe, Michael S. Goodson, Nancy Kelley‐Loughnane, Niall P. Hyland, John F. Cryan, Gerard Clarke The Journal of Physiology.2023; 601(20): 4491. 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
INVESTIGATION OF THE ROLE OF STRESS IN MALE INFERTILITY AND THE EFFECT OF CURRENT MELATONIN HORMONE TREATMENTS İshak GÖKÇEK, Leyla AYDIN Veteriner Farmakoloji ve Toksikoloji Derneği Bülteni.2023; 14(1): 36. CrossRef
The double burden of malnutrition and environmental enteric dysfunction as potential factors affecting gut-derived melatonin in children under adverse environments Alane N. Bezerra, Caroline L. Peixoto, Synara C. Lopes, Veralice M. S. Bruin, Pedro Felipe C. Bruin, Reinaldo B. Oriá Frontiers in Nutrition.2023;[Epub] CrossRef
Melatonin: Both a Messenger of Darkness and a Participant in the Cellular Actions of Non-Visible Solar Radiation of Near Infrared Light Dun-Xian Tan, Russel J. Reiter, Scott Zimmerman, Ruediger Hardeland Biology.2023; 12(1): 89. CrossRef
Glucocorticoids coordinate the bladder peripheral clock and diurnal micturition pattern in mice Ichiro Chihara, Hiromitsu Negoro, Jin Kono, Yoshiyuki Nagumo, Haruki Tsuchiya, Kosuke Kojo, Masanobu Shiga, Ken Tanaka, Shuya Kandori, Bryan J. Mathis, Hiroyuki Nishiyama Communications Biology.2023;[Epub] CrossRef
The Microbiota-Dependent Worsening Effects of Melatonin on Gut Inflammation Jefferson Luiz da Silva, Lia Vezenfard Barbosa, Camila Figueiredo Pinzan, Viviani Nardini, Irislene Simões Brigo, Cássia Aparecida Sebastião, Jefferson Elias-Oliveira, Vânia Brazão, José Clóvis do Prado Júnior, Daniela Carlos, Cristina Ribeiro de Barros C Microorganisms.2023; 11(2): 460. CrossRef
The Effects of Stress and Diet on the “Brain–Gut” and “Gut–Brain” Pathways in Animal Models of Stress and Depression Mauritz F. Herselman, Sheree Bailey, Larisa Bobrovskaya International Journal of Molecular Sciences.2022; 23(4): 2013. 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
Protective Effects and Mechanisms of Melatonin on Stress Myocardial Injury in Rats Jia-yao Chen, Ting Li, Jiao-ling Wang, Zhan-le Wang, Yun Zhang, Lin-quan Zang Journal of Cardiovascular Pharmacology.2022; 80(3): 417. CrossRef
Rescue of social deficits by early-life melatonin supplementation through modulation of gut microbiota in a murine model of autism Xia Liu, Yi Cui, Yuhan Zhang, Guo Xiang, Meng Yu, Xianshu Wang, Bin Qiu, Xin-gang Li, Wei Liu, Di Zhang Biomedicine & Pharmacotherapy.2022; 156: 113949. CrossRef
Roles of PRR-Mediated Signaling Pathways in the Regulation of Oxidative Stress and Inflammatory Diseases Pengwei Li, Mingxian Chang International Journal of Molecular Sciences.2021; 22(14): 7688. CrossRef