Journal Article

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

Winters, Andrew D., Angoa-Pérez, Mariana, Kuhn, Donald M., Zagorac, Branislava, Ahmad, Madison, Greenberg, Jonathan M., Theis, Kevin R.

2020

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Addiction / Amphetamines / Analogs / Analysis / Animals / Bath products / Biochemistry / Biology and Life Sciences / Brain research / Cocaine / Collection Review / Computer and Information Sciences / Deoxyribonucleic acid / Designer Drugs - administration & dosage / Designer Drugs - adverse effects / Diabetes mellitus / Diabetes therapy / Digestive system / Dingell, John D / Disease / DNA / DNA sequencing / DNA, Bacterial - isolation & purification / Drug abuse / Drug addiction / Drug interactions / Drugs / Ecology and Environmental Sciences / Female / Gastrointestinal Microbiome - drug effects / Gastrointestinal Microbiome - genetics / Gene sequencing / Genes / Genomes / Gut microbiota / Gut-brain axis / Hallucinogenic drugs / Health / Health aspects / Illegal drugs / Immunology / Infection / Intestinal microflora / Laboratory animals / Medicine / Medicine and Health Sciences / Methamphetamine / Methamphetamine - administration & dosage / Methamphetamine - adverse effects / Methamphetamine - analogs & derivatives / Mice / Microbiomes / Microbiota / Models, Animal / Neurosciences / Neurotoxicity / Propiophenones - administration & dosage / Propiophenones - adverse effects / Psychiatry / Psychotropic drugs / Psychotropic Drugs - administration & dosage / Psychotropic Drugs - adverse effects / R&D / Research & development / RNA / RNA, Ribosomal, 16S - genetics / rRNA 16S / Salts / Social Sciences / Stimulants / Substance abuse treatment / Time dependence