The influence of the host microbiome on 3,4-methylenedioxymethamphetamine (MDMA)-induced hyperthermia and vice versa
Emily Ridge, Sudhan Pachhain, S. Choudhury, Sara R. Bodnar, Ray A. Larsen, V. Phuntumart, J. E. Sprague
Scientific Reports March 13, 2019 DOI: 10.1038/s41598-019-40803-3 via Semantic Scholar
Summary
The gut microbiome and TGR5 bile acid receptors contribute to the life-threatening hyperthermia caused by MDMA. Male rats given antibiotics to reduce gut bacteria showed a weaker hyperthermic response to MDMA. MDMA increased expression of uncoupling protein 1 and TGR5 in brown adipose tissue and skeletal muscle, and UCP3 in skeletal muscle; antibiotics blunted these increases. Blocking TGR5 with triamterene or deiodinase II with iopanoic acid also reduced MDMA-induced hyperthermia. MDMA enriched a Proteus mirabilis strain in the ceca of rats not given antibiotics. The findings suggest gut microbiota play a role in MDMA-mediated hyperthermia and that MDMA rapidly alters gut microbiome composition.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats |
| Keywords | Medicine Chemistry Biology Environmental science |
| Citations | 25 |
| Key finding | Gut microbiota and TGR5 bile acid receptors contribute to MDMA-induced hyperthermia, and MDMA rapidly remodels gut microbiome composition. |
Abstract
Hyperthermia induced by 3,4-methylenedioxymethamphetamine (MDMA) can be life-threatening. Here, we investigate the role of the gut microbiome and TGR5 bile acid receptors in MDMA-mediated hyperthermia. Fourteen days prior to treatment with MDMA, male Sprague-Dawley rats were provided water or water treated with antibiotics. Animals that had received antibiotics displayed a reduction in gut bacteria and an attenuated hyperthermic response to MDMA. MDMA treated animals showed increased uncoupling protein 1 (UCP1) and TGR5 expression levels in brown adipose tissue and skeletal muscle while increased expression of UCP3 was observed only in skeletal muscle. Antibiotics prior to MDMA administration significantly blunted these increases in gene expression. Furthermore, inhibition of the TGR5 receptor with triamterene or of deiodinase II downstream of the TGR5 receptor with iopanoic acid also resulted in the attenuation of MDMA-induced hyperthermia. MDMA-treatment enriched the relative proportion of a Proteus mirabilis strain in the ceca of animals not pre-treated with antibiotics. These findings suggest a contributing role for the gut microbiota in MDMA-mediated hyperthermia and that MDMA treatment can trigger a rapid remodeling of the composition of the gut microbiome.