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The influence of the host microbiome on 3,4-methylenedioxymethamphetamine (MDMA)-induced hyperthermia and vice versa

Emily A Ridge1, Sudhan Pachhain2, Sayantan Roy Choudhury2

  • 1The Ohio Attorney General's Center for the Future of Forensic Science, Bowling Green State University, Bowling Green, OH, 43403, USA.

Scientific Reports
|March 15, 2019
PubMed

Insights

The gut microbiome influences 3,4-methylenedioxymethamphetamine (MDMA) induced hyperthermia. Antibiotics reduced gut bacteria, blunting MDMA

Area of Science:

  • Pharmacology
  • Microbiology
  • Physiology

Background:

  • 3,4-methylenedioxymethamphetamine (MDMA) can cause life-threatening hyperthermia.
  • The gut microbiome's role in MDMA-induced hyperthermia is not well understood.
  • TGR5 bile acid receptors are implicated in metabolic regulation.

Purpose of the Study:

  • To investigate the role of the gut microbiome in MDMA-induced hyperthermia.
  • To examine the involvement of TGR5 bile acid receptors in this process.
  • To understand the impact of MDMA on gut microbiome composition.

Main Methods:

  • Male Sprague-Dawley rats were treated with antibiotics or given a control solution 14 days prior to MDMA administration.
  • Gene expression levels of UCP1, UCP3, and TGR5 were measured in brown adipose tissue and skeletal muscle.
  • TGR5 receptor and deiodinase II were inhibited using specific pharmacological agents.
  • Gut microbiome composition was analyzed using 16S rRNA sequencing.

Main Results:

  • Antibiotic treatment reduced gut bacteria and attenuated MDMA-induced hyperthermia.
  • MDMA increased UCP1 and TGR5 expression in brown adipose tissue and skeletal muscle, which was blunted by antibiotics.
  • Inhibition of TGR5 or deiodinase II attenuated MDMA hyperthermia.
  • MDMA treatment enriched Proteus mirabilis in the gut microbiome of non-antibiotic treated animals.

Conclusions:

  • The gut microbiota plays a significant role in MDMA-mediated hyperthermia.
  • MDMA treatment rapidly alters gut microbiome composition.
  • The TGR5 receptor pathway is involved in MDMA-induced hyperthermia.

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