You are what you vape: Implications of THC chronic self-administration in changes in the gut microbiome of rats.

Abstract

Abstract Vaping of cannabis and its constituents, such as Δ9-tetrahydrocanabinol (THC), has been promoted as a safer alternative to smoked cannabis. Nevertheless, chronic effect of THC vaping in gut microbiome modulation and its effect of health and or disease is still largely unknown. Hence, this project intends to study the effect of chronic THC vapor self-administration on changes in the gut microbiome of Sprague-Dawley rats. Animals were randomly assigned to either vehicle vapor (100% propylene glycol [PG]) or THC vapor groups and were allowed to self-administer PG or THC vapor puffs in operant chambers for one hour on intermittent days for a total of nine months. At the end of this period, a subset of rats was tested for anxiety-like behavior using the open field test. Afterwards, rats were euthanized with isoflurane overdose and rapid decapitation. Feces, metabolic and immune organs, and serum were collected at the time of necropsy. Fecal DNA was extracted, and relative bacterial gut abundance was determined sequencing 16S hypervariable region V4. Rats exposed to THC vape show anxiety-like behavior in the open field test, when compared with the PG exposed group. This change in behavior is also accompanied by an imbalance in their Firmicutes/Bacteroides ratio, having less Firmicutes and more Bacteroides, specifically members of the Muribaculaceae family. Currently, the effect of this dysbiosis on immune markers expression, such as: CCL2, IL-6, TNF-a, IFNa, IFNb, MX1 and TRAIL, are being studied to determine if there is any disruption on immune homeostasis caused by altered microbiome abundance. R01DA052859-03S1