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.阿片类药物诱导的肠功能障碍（Opioid-induced bowel dysfunction, OIBD）是用于急慢性疼痛管理的阿片类药物治疗相关的重大临床难题。本研究探究了羟考酮治疗对肠道菌群结构与功能的影响，重点关注微生物多样性、分类学组成以及短链脂肪酸（short-chain fatty acid, SCFA）的产生情况。本交叉研究中的健康受试者先后接受安慰剂与羟考酮治疗，研究人员采用16S rRNA基因扩增子测序和宏基因组鸟枪法对微生物群落结构进行分析（临床试验注册号：EudraCT: 2013-001540-60）。 研究结果显示，接受羟考酮治疗的受试者的微生物丰富度和均匀度均显著降低，分类学组成发生改变，包括嗜黏蛋白阿克曼氏菌（Akkermansia muciniphila）丰度升高。功能分析揭示了短链脂肪酸生成通路的变化，羟考酮处理样本中的乙酸、丁酸和丙酸浓度均有所升高。典范对应分析（Canonical correspondence analysis, CCA）证实了治疗诱导的微生物群落聚类模式发生偏移。 本研究揭示了肠道菌群在阿片类药物诱导肠功能障碍病理生理过程中的潜在作用，为阿片类药物治疗影响的微生物生物标志物和功能通路提供了新见解。研究结果强调了靶向菌群的干预手段在缓解阿片类药物使用所致胃肠道不良反应方面的必要性。 数据集基于16S rRNA基因扩增子数据（欧洲核苷酸档案馆（European Nucleotide Archive, ENA）登录号：PRJEB96047），我们选取了3名受试者在首个治疗周期接受安慰剂、第二治疗周期接受羟考酮的每个治疗周期第5天的样本，用于宏基因组测序；样本制备遵循制造商方案，使用Native Barcoding Kit 24 V14（英国牛津纳米孔科技公司）完成。将6份样本以等摩尔浓度混合为2个混合库，每个混合库包含3个文库，随后在2张PromethION R.10.4.1流通池（英国牛津纳米孔科技公司）上并行测序72小时。 本次上传内容包含分箱后的宏基因组及其元数据。