Oxycodone intervention causes immediate shift in microbiota composition and fermentation activity in healthy humans

Opioid-induced bowel dysfunction (OIBD) is a significant clinical challenge associated with opioid therapy for acute and chronic pain management. This study investigates the impact of oxycodone treatment on gut microbiome structure and function, focusing on microbial diversity, taxonomic composition, and short-chain fatty acid (SCFA) production. Healthy participants in a cross-over study received placebo and oxycodone treatments, and microbial community structure was analysed using 16S rRNA gene amplicon sequencing and shotgun metagenomics (EudraCT: 2013-001540-60). Results revealed significant reductions in microbial richness and evenness in oxycodone-treated participants, with altered taxonomic composition, including increased abundance of Akkermansia muciniphila. Functional analysis identified changes in SCFA production pathways, with elevated concentrations of acetate, butyrate, and propionate in oxycodone-treated samples. Canonical correspondence analysis (CCA) confirmed treatment-induced shifts in microbial community clustering. This study highlights the potential role of the gut microbiome in the pathophysiology of OIBD, providing insights into microbial biomarkers and functional pathways affected by opioid therapy. Findings underscore the need for microbiome-targeted interventions to mitigate the gastrointestinal side effects of opioid use. DATA: Based on the 16S rRNA gene amplicon data (European Nucleotide Archive (ENA) accession number PRJEB96047), samples from the fifth day of each treatment period from three participants receiving placebo in the first treatment period and oxycodone in the second treatment period were chosen for metagenomic sequencing and prepared using the Native Barcoding Kit 24 V14 (Oxford Nanopore Technologies, United Kingdom) following the manufacturer's protocol. The six samples were equimolarly pooled into two pools, each containing three libraries and sequenced in parallel on two PromethION R.10.4.1 flow cells (Oxford Nanopore Technologies, United Kingdom) for 72 hours. This upload contains the binned metagenomes including metadata.