Effects of 3,4-methylenedioxymethamphetamine on the gut microbiota and metabolites in the small intestine, cecum, and colon of male rats

Dan Xu; Akifumi Eguchi; Rumi Murayama; Guilin Liu; Mingming Zhao; Tingting Zhu; Yi Cai; Yong Yue; Xiayun Wan; Yuko Fujita; Chisato Mori; Kenji Hashimoto

doi:10.1016/j.pnpbp.2024.111223

Effects of 3,4-methylenedioxymethamphetamine on the gut microbiota and metabolites in the small intestine, cecum, and colon of male rats

Prog Neuropsychopharmacol Biol Psychiatry. 2024 Dec 17:111223. doi: 10.1016/j.pnpbp.2024.111223. Online ahead of print.

Authors

Dan Xu¹, Akifumi Eguchi², Rumi Murayama³, Guilin Liu⁴, Mingming Zhao⁵, Tingting Zhu⁵, Yi Cai⁶, Yong Yue⁶, Xiayun Wan⁶, Yuko Fujita⁶, Chisato Mori⁷, Kenji Hashimoto⁸

Affiliations

¹ Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan; Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
² Department of Sustainable Health Science, Chiba University Center for Preventive Medical Sciences, Chiba 263-8522, Japan.
³ Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan; Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
⁴ Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan; Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao 266100, China.
⁵ Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan; Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
⁶ Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan.
⁷ Department of Sustainable Health Science, Chiba University Center for Preventive Medical Sciences, Chiba 263-8522, Japan; Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
⁸ Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan. Electronic address: [email protected].

PMID: 39701173
DOI: 10.1016/j.pnpbp.2024.111223

Abstract

3,4-Methylenedioxymethamphetamine (MDMA; Ecstasy) is a widely abused recreational drug that has also gained interest for potential clinical applications in mental health. With the growing recognition of gut microbiota's role in mental health, this study examined whether repeated oral MDMA administration could affect gut microbiota in the small intestine, cecum, and colon of male rats. Repeated oral MDMA administration (10 mg/kg/day for 14 days) caused significant changes in the gut microbiota across these regions, with distinct effects observed in each. PICRUSt2 analysis revealed significant alterations in several metabolic pathways in these regions, indicating potential shifts in microbial functional capabilities associated with MDMA treatment. Untargeted metabolomics analysis revealed that MDMA significantly altered levels of two metabolites-ferulic acid and methylmalonic acid-in the colon, without changes in the blood, small intestine, or cecum. Notably, methylmalonic acid levels in the colon positively correlated with Lawsonibacter and Oscillibacter. These findings suggest that repeated oral MDMA treatment can alter gut microbiota composition across intestinal regions, potentially contributing to its pharmacological effects.

Keywords: Entactogen; Gastrointestinal tract; Gut microbiota; MDMA; Metabolites.