Differential effects of synthetic psychoactive cathinones and amphetamine stimulants on the gut microbiome in mice


Autoři: Mariana Angoa-Pérez aff001;  Branislava Zagorac aff001;  Andrew D. Winters aff003;  Jonathan M. Greenberg aff003;  Madison Ahmad aff003;  Kevin R. Theis aff003;  Donald M. Kuhn aff001
Působiště autorů: Research and Development Service, John D. Dingell VA Medical Center, Detroit, Michigan, United States of America aff001;  Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan, United States of America aff002;  Department of Biochemistry, Microbiology and Immunology, Wayne State University School of Medicine, Detroit, Michigan, United States of America aff003;  Perinatal Research Initiative in Maternal, Perinatal and Child Health, Wayne State University School of Medicine, Detroit, Michigan, United States of America aff004
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Collection Review
doi: 10.1371/journal.pone.0227774

Souhrn

The list of pharmacological agents that can modify the gut microbiome or be modified by it continues to grow at a high rate. The greatest amount of attention on drug-gut microbiome interactions has been directed primarily at pharmaceuticals used to treat infection, diabetes, cardiovascular conditions and cancer. By comparison, drugs of abuse and addiction, which can powerfully and chronically worsen human health, have received relatively little attention in this regard. Therefore, the main objective of this study was to characterize how selected synthetic psychoactive cathinones (aka “Bath Salts”) and amphetamine stimulants modify the gut microbiome. Mice were treated with mephedrone (40 mg/kg), methcathinone (80 mg/kg), methamphetamine (5 mg/kg) or 4-methyl-methamphetamine (40 mg/kg), following a binge regimen consisting of 4 injections at 2h intervals. These drugs were selected for study because they are structural analogs that contain a β-keto substituent (methcathinone), a 4-methyl group (4-methyl-methamphetamine), both substituents (mephedrone) or neither (methamphetamine). Mice were sacrificed 1, 2 or 7 days after treatment and DNA from caecum contents was subjected to 16S rRNA sequencing. We found that all drugs caused significant time- and structure-dependent alterations in the diversity and taxonomic structure of the gut microbiome. The two phyla most changed by drug treatments were Firmicutes (methcathinone, 4-methyl-methamphetamine) and Bacteriodetes (methcathinone, 4-methyl-methamphetamine, methamphetamine, mephedrone). Across time, broad microbiome changes from the phylum to genus levels were characteristic of all drugs. The present results signify that these selected psychoactive drugs, which are thought to exert their primary effects within the CNS, can have profound effects on the gut microbiome. They also suggest new avenues of investigation into the possibility that gut-derived signals could modulate drug abuse and addiction via altered communication along the gut-brain axis.

Klíčová slova:

Drug abuse – Drug synthesis – Drug therapy – Microbial taxonomy – Microbiome – Ribosomal RNA – Simpson index – Amphetamines


Zdroje

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