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Oliceridine and morphine differentially modulate the gut microbiota–intestinal barrier axis in a rat postoperative pain model

Year: 2026

Type: article

Abstract: Background: Oliceridine is a novel G protein-biased μ-opioid receptor agonist with potentially improved gastrointestinal tolerability compared with conventional opioids. However, its impact on postoperative intestinal homeostasis-specifically the gut microbiota and intestinal barrier-remains poorly understood. Methods: A postoperative pain model was established in male Sprague-Dawley rats using the Brennan plantar incision method. Animals were randomly assigned to four groups: non-incision control (CON), plantar incision plus normal saline, plantar incision plus oliceridine (OLI, 1 mg/kg subcutaneous bolus followed by continuous infusion at 1 mg/kg/day for 72 h), and plantar incision plus morphine (MF, 5 mg/kg subcutaneous bolus followed by continuous infusion at 5 mg/kg/day for 72 h). Analgesic efficacy was assessed by mechanical withdrawal threshold (MWT) and area under the curve (AUC). Intestinal morphology, epithelial Claudin-1 expression by immunofluorescence (n = 4 per group), gut microbiota composition (16S rRNA gene sequencing, n = 6 per group), and host ileal transcriptomic profiles (RNA-seq, n = 3 per group) were evaluated. Results: -related taxa and host genes linked to barrier function and metabolism (|r| > 0.6, P < 0.01). Conclusion: -related signal, but no genus-level differences remained significant after multiple-testing correction. Oliceridine was associated with a distinct ileal transcriptomic profile and higher Claudin-1 fluorescence intensity than morphine, although histological injury did not differ between the two groups. The functional significance of these molecular differences requires further investigation.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1907666