PMID- 30867489
OWN - NLM
STAT- MEDLINE
DCOM- 20200929
LR  - 20210109
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 9
IP  - 1
DP  - 2019 Mar 13
TI  - The influence of the host microbiome on 3,4-methylenedioxymethamphetamine 
      (MDMA)-induced hyperthermia and vice versa.
PG  - 4313
LID - 10.1038/s41598-019-40803-3 [doi]
LID - 4313
AB  - 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.
FAU - Ridge, Emily A
AU  - Ridge EA
AD  - The Ohio Attorney General's Center for the Future of Forensic Science, Bowling 
      Green State University, Bowling Green, OH, 43403, USA.
FAU - Pachhain, Sudhan
AU  - Pachhain S
AD  - The Department of Biological Sciences, Bowling Green State University, Bowling 
      Green, OH, 43403, USA.
FAU - Choudhury, Sayantan Roy
AU  - Choudhury SR
AD  - The Department of Biological Sciences, Bowling Green State University, Bowling 
      Green, OH, 43403, USA.
FAU - Bodnar, Sara R
AU  - Bodnar SR
AD  - The Ohio Attorney General's Center for the Future of Forensic Science, Bowling 
      Green State University, Bowling Green, OH, 43403, USA.
FAU - Larsen, Ray A
AU  - Larsen RA
AD  - The Department of Biological Sciences, Bowling Green State University, Bowling 
      Green, OH, 43403, USA.
FAU - Phuntumart, Vipaporn
AU  - Phuntumart V
AD  - The Department of Biological Sciences, Bowling Green State University, Bowling 
      Green, OH, 43403, USA.
FAU - Sprague, Jon E
AU  - Sprague JE
AD  - The Ohio Attorney General's Center for the Future of Forensic Science, Bowling 
      Green State University, Bowling Green, OH, 43403, USA. jesprag@bgsu.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190313
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Gpbar1 protein, rat)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Uncoupling Protein 1)
RN  - 0 (Uncoupling Protein 3)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Fever/chemically induced/*microbiology
MH  - *Hyperthermia, Induced
MH  - Male
MH  - *Microbiota/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Proteus mirabilis/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, G-Protein-Coupled/metabolism
MH  - Uncoupling Protein 1/metabolism
MH  - Uncoupling Protein 3/metabolism
PMC - PMC6416279
COIS- The authors declare no competing interests.
EDAT- 2019/03/15 06:00
MHDA- 2020/09/30 06:00
PMCR- 2019/03/13
CRDT- 2019/03/15 06:00
PHST- 2018/07/24 00:00 [received]
PHST- 2019/02/18 00:00 [accepted]
PHST- 2019/03/15 06:00 [entrez]
PHST- 2019/03/15 06:00 [pubmed]
PHST- 2020/09/30 06:00 [medline]
PHST- 2019/03/13 00:00 [pmc-release]
AID - 10.1038/s41598-019-40803-3 [pii]
AID - 40803 [pii]
AID - 10.1038/s41598-019-40803-3 [doi]
PST - epublish
SO  - Sci Rep. 2019 Mar 13;9(1):4313. doi: 10.1038/s41598-019-40803-3.