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Bile acids and the gut microbiome are involved in the hyperthermia mediated by 3,4-methylenedioxymethamphetamine

Srishti Rana1, Jeremy R Canfield2, Christopher S Ward1

  • 1Department of Biological Sciences, Bowling Green State University, Bowling Green, OH, 43403, USA.

Scientific Reports
|June 24, 2024
PubMed

Insights

The gut microbiome

Area of Science:

  • Pharmacology
  • Microbiology
  • Toxicology

Background:

  • Phenethylamines, like MDMA, can cause dangerous hyperthermia.
  • Sympathetic nervous system activation and uncoupling proteins are known mediators.
  • The gut microbiome's role in this hyperthermia is a recent area of investigation.

Purpose of the Study:

  • To test the hypothesis that gut microbiome-produced bile acids (BAs) are essential for phenethylamine-induced hyperthermia (PIH).

Main Methods:

  • Rats were treated with MDMA (3,4-methylenedioxymethamphetamine) after antibiotic pretreatment to deplete BAs.
  • Serum BA concentrations and body temperature were measured.
  • Gut microbiome composition and function were analyzed using 16S rRNA sequencing and bioinformatics.

Main Results:

  • MDMA induced hyperthermia and reduced serum BA levels.
  • Antibiotic pretreatment depleted BAs, reduced microbiome diversity, and resulted in hypothermia following MDMA.
  • Bacterial genes related to BA metabolism were less abundant in antibiotic-treated rats.

Conclusions:

  • Gut bacterial-derived bile acids may play a critical role in MDMA-induced hyperthermia.
  • Modulating the gut microbiome could be a potential strategy to mitigate PIH.

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