Comparative Analysis of Opioid-induced Microbiome Alterations in Rat Small Intestine, Cecum, and Colon

Background: Trillions of bacteria, archaea, fungi, and viruses comprise the animal microbiome and virome. The composition and diversity of these complex communities have a profound impact on the health of their animal host. Conversely, microbiome profiles can be affected by multiple host factors such as diet, health, or medication. Embedded in these communities might be groupings such as individual bacterial species/strains or consortia that have key roles and could serve as biomarkers for host health and disease.

Methods: We have been collecting microbiota and/or microbiome profiles from rat small intestine, cecum, and colon after chronic oxycodone administration to assess the impact of the drug on the resident microbial communities and identify such specific markers. Next-generation sequencing systems are used for 16S ribosomal RNA analyses and whole-genome shotgun metagenomics to determine taxonomic profiles and predict functional profiles of the microbial communities.

Results: Alpha and beta diversity analyses of the microbiota showed differences in the gastrointestinal regions when using location, sex, or treatment as metadata. Differential abundance analyses of datasets from control and oxycodone-treated animals revealed specific alterations in the microbiota composition within these experimental groups. Examples of workflows and bioinformatic approaches are presented that illustrate how biomarker discovery within different gastrointestinal regions could lead to deeper understanding of the impact oxycodone has on the animal and human microbiomes.

Conclusions: Correlation of microbiome profiles with host metadata will aid in the identification of potential biomarkers of oxycodone use in the different host organ environments. The resulting biomarker discoveries may aid in diagnosis, prevention, and treatment of drug-induced gastrointestinal dysbiosis.