The gut microbiome is associated with cocaine behavior and predicts addiction vulnerability in adult male rats

The gut-brain axis is a bi-directional communication system through which microbial communities in the gut interact with the nervous system, perhaps influencing neuropsychiatric disorders such as drug abuse. This study used behavioral data and biological samples from the Cocaine Biobank to test the hypothesis that the gut microbiota can predict and reflect susceptibility to cocaine reinforcement. Adult male heterogenous rats were catheterized and allowed to self-administer cocaine in short-access sessions (2 hr/day, 10 days, 0.5 mg/kg per intravenous infusion), followed by progressive ratio (PR) tests, long-access sessions (6 hr/day, 14 days), and alternating blocks of PR, long-access, and footshock testing. Fecal samples were collected at three time points and bacterial 16s rRNA genes were sequenced to profile the microbiota. As expected, cocaine-related behavior varied among subjects, such that a quartile split identified low and high responders on each measure, as well as an overall addiction index. Although beta diversity in the microbiota at baseline and after short access did not predict membership in high or low addiction quartiles, linear discriminant analysis (LDA) identified taxa that were more robustly represented in low or high responders. Beta diversity after long access was different among quartiles, as were several specific taxa. Investigation of baseline differences revealed that high relative abundance of Akkermansia muciniphila predicted future low response rates, whereas Ruminococcaceae predicted high response. This study is the first to report that microbiota variability reflects levels of cocaine intake and that microbial profiles might facilitate diagnosis and identify risk factors predictive of drug vulnerability. Significance StatementMicrobial organisms inhabiting the gut of animals appear to influence organismal function through various signaling pathways, ultimately affecting behavior and disease vulnerability. This experiment investigates links between gut bacteria and vulnerability to addiction-related behaviors in adult male rats. Not only did gut bacterial profiles change as a result of cocaine intake but also gut bacterial profiles before any exposure to cocaine predicted which animals would be high or low addiction-prone individuals. These results suggest that microbial profiles might facilitate diagnosis and identify risk factors predictive of drug addiction.