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

Progress in neuro-psychopharmacology & biological psychiatry  – January 10, 2025

Source: PubMed

Summary

The entactogen MDMA affects more than just the brain - it significantly impacts the gut microbiota throughout the gastrointestinal tract. Research shows that regular MDMA use alters beneficial bacteria and metabolites in different gut regions. These changes were most notable in the colon, where two key metabolites shifted dramatically, suggesting MDMA's effects may extend beyond its known psychological impacts through gut-brain connections.

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.

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