Short-term oxycodone exposure produces delayed and persistent gut microbiome disruption in mice

Area of Science:

• Microbiology
• Pharmacology
• Host-Microbiome Interactions

Background:

• The gut microbiome plays a crucial role in host homeostasis.
• Opioid-induced gut dysbiosis is recognized, but long-term recovery dynamics are unclear.
• Short-term opioid exposure is often assumed to cause only transient gut microbiome disruption.

Purpose of the Study:

• To characterize the temporal dynamics of the fecal microbiota following a brief oxycodone regimen in mice.
• To determine the long-term recovery patterns of the gut microbiome after short-term opioid exposure.

Main Methods:

• Male C57BL/6J mice were administered oxycodone (5mg/kg, BID) for 3 days.
• Fecal samples were collected at baseline, day 3, 10, 17, and 70.
• 16S rRNA gene sequencing was used to analyze microbial community structure and diversity.

Main Results:

• While acute phases showed subtle shifts, significant gut microbial community disruption emerged later, by day 17.
• By day 70, both alpha and beta diversity remained significantly altered compared to controls.
• Specific taxa like *Akkermansia* and *Marvinbryantia* were enriched, while *Eubacterium_xylanophilum* was depleted at day 70.

Conclusions:

• Even brief oxycodone exposure triggers persistent, non-recovering gut dysbiosis.
• Microbiome recovery exceeded two months in mice, suggesting potential long-term risks for patients on short-term opioid courses.
• Delayed and persistent alterations indicate that short-term opioid use may lead to longer-lasting gut microbiome remodeling than previously assumed.