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
Progress in neuro-psychopharmacology & biological psychiatry January 10, 2025 DOI: 10.1016/j.pnpbp.2024.111223 via PubMed
Summary
AI-generated from the abstractRepeated oral administration of MDMA (10 mg/kg/day for 14 days) to male rats significantly altered gut microbiota composition in the small intestine, cecum, and colon, with distinct effects in each region. Analysis of microbial functional capabilities indicated shifts in several metabolic pathways. Untargeted metabolomics showed that MDMA changed levels of two metabolites in the colon—ferulic acid and methylmalonic acid—without affecting levels in blood, small intestine, or cecum. Methylmalonic acid levels in the colon positively correlated with the bacteria Lawsonibacter and Oscillibacter. These results suggest that repeated MDMA treatment can modify gut microbiota across intestinal regions, which may contribute to its pharmacological effects.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Male rats |
| Intervention | MDMA |
| Dose | 10 mg/kg/day for 14 days |
| Duration | 14 days |
| Topics | MDMA |
| Keywords | Entactogen Gastrointestinal tract Gut microbiota Metabolites MDMA Ecstasy |
| Citations | 4 |
| Key finding | Repeated oral MDMA administration altered gut microbiota composition and metabolic pathways in the small intestine, cecum, and colon of male rats, and changed levels of ferulic acid and methylmalonic acid in the colon. |
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.