Alterations in the Gut Microbiota of Rats Chronically Exposed to Volatilized Cocaine and Its Active Adulterants Caffeine and Phenacetin

Abstract

A role of the gut microbiota in influencing brain function and emotional disorders has been suggested. However, only a few studies have investigated the gut microbiota in the context of drug addiction.Cocaine can be smoked (i.e., crack or coca paste) and its consumption is associated with a very high abuse liability and toxicity. We have recently reported that cocaine base seized samples contained caffeine and phenacetin as main active adulterants, which may potentiate its motivational, reinforcing, and toxic effects. However, the effect of volatilized cocaine and adulterants on the gut microbiota remained unknown. In the present study, we evaluated the effect of volatilized cocaine and two adulterants on the structure, diversity, and functionality of the gut microbiota in rats. Animals were chronically exposed to the fume of cocaine, caffeine, and phenacetin during 14 days. At the end of the treatment, feces were collected and the structure, composition, and functional predictions of the gut microbiota were analyzed. Cocaine significantly decreased the community richness and diversity of the gut microbiota while both cocaine and phenacetin drastically changed its composition. Phenacetin significantly increased the Firmicutes-Bacteroidetes ratio compared to the control group. When the predicted metagenome functional content of the bacterial communities was analyzed, all the treatments induced a dramatic decrease of the aromatic amino acid decarboxylase gene. Our findings suggest that repeated exposure to volatilized cocaine, as well as to the adulterants caffeine and phenacetin, leads to changes in the gut microbiota. Future studies are needed to understand the mechanisms underlying these changes and how this information may support the development of novel treatments in drug addiction.

Differences in Gut Microbial Diversity are Driven by Drug Use and Drug Cessation by Either Compulsory Detention or Methadone Maintenance Treatment

“…In this study, Bacteroidetes (2,180,793 reads) and Firmicutes (1,320,089 reads) comprised 89.85% of all sequences, although the DU subjects had a significantly higher proportion of Firmicutes than the CD group. This finding is comparable to that of Scorza et al (2019), in which they found that cocaine and phenacetin treatment groups had higher Firmicutes compared with healthy people [25]. We also found that Bifidobacterium and Lactobacillus had a higher relative abundance in the MP group than in the CD and DU groups, likely related to a selection for probiotic lactic acid bacteria induced by a higher consumption of milk and dairy in the MP group than in the other two groups.…”

“…All PCR products were sequenced by MiSeq reagent kit version 3 (Illumina, San Diego, CA, USA). Similarly, detailed sequencing methods can be found in the following literature [25,[38][39][40][41][42].…”

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

“…In general, the number of discriminant taxa for all study drugs diminished over time, reaching the fewest number by 7 days post-treatment. Studies with other psychostimulants affecting the dopaminergic system include reports of chronic cocaine treatment leading to similar beta diversity alterations, and enrichments of members of Lachnospiracaceae and Ruminococcaceae [61].…”

A potential role for the gut microbiome in substance use disorders

“…Literature-Because cocaine is frequently smoked, Scorza et al (2019) examined the effects of volatilized cocaine as well as caffeine and phenacetin, two common adulterants in cocaine, by exposing rats to the fume of these compounds for 14 days. Significant shifts in fecal microbial communities were noted in cocaine and phenacetintreated rats compared to controls, and stool samples from cocaine-treated rats exhibited elevated microbial expression of genes involved in the synthesis of the SCFA butyrate.…”

“…Caffeine-treatment alone, however, had little effect on the composition of the fecal microbiome. Further research should examine whether these changes in gut microbial composition are associated with altered behavioral response to cocaine or phenacetin (Scorza et al 2019).…”