Oxycodone self-administration and genetic background exert community-specific effects in the gut microbiome

The gut microbiome and genetic factors contribute to several opioid-related phenotypes in humans and animal models. Here, we examined the effects of genetic background and oxycodone self-administration on the gut microbiome in two genetically divergent rat strains. ACI/EurMcwi and M520/N rats were trained to self-administer oxycodone or saline. Males and females from both strains acquired and escalated oxycodone self-administration, with M520/N rats administering more oxycodone than ACI/EurMcwi rats. Saline self-administration was influenced by a strain-sex interaction, with M520/N females consuming more than any other saline-administering animals. Following the self-administration period, fecal and cecal samples were collected to examine the effects of genetic background, sex, and oxycodone on the gut microbiome. Measures of alpha diversity in the fecal and cecal microbiomes were influenced by strain and sex, but not oxycodone. Beta diversity analyses demonstrated that strain and oxycodone alter the structure of the fecal and cecal microbiomes, while sex had more limited effects. Both oxycodone and strain exerted community-specific effects on gut microbiome composition, with 15 taxa differing between self-administration groups and 51 taxa differing between strains. These findings demonstrate that genetic background influences self-administration phenotypes, and both host genetics and oxycodone influence the diversity and composition of the gut microbiome.