Gut microbiota dysbiosis and hepatic inflammation in morphine dependence and withdrawal: insights from a rat model

BACKGROUND: Opioid dependence, particularly morphine, has been linked to gut microbiota dysbiosis and systemic inflammation, yet the interplay between gut microbial alterations and hepatic inflammatory responses remains poorly understood. METHODS: Fifty male Wistar rats were separated into two groups, one received escalating morphine doses (5 to 30 mg/kg over 10 days), while the other acted as a saline control. Fecal samples were collected at baseline, on days 5 and 10 of treatment, and after a 10-day withdrawal. DNA was extracted for qPCR analysis of Lactobacillus, Bifidobacterium, Clostridium, Bacteroides, and Faecalibacterium. Liver tissues were examined for inflammatory markers (TNF-α, IFN-γ, IL-6, NF-κB) using RT-qPCR after treatment and withdrawal. RESULTS: A significant decline in Lactobacillus (P = 0.011) and Bifidobacterium (P = 0.003) following morphine treatment, with partial recovery observed after withdrawal (P = 0.014; P = 0.0009), yet levels remained below baseline. Conversely, Clostridium levels increased significantly during treatment (P = 0.0001), persisting at elevated levels post-withdrawal (P = 0.0001). Bacteroides and Faecalibacterium also exhibited decreased abundances during morphine treatment (P > 0.05; P = 0.00009), with limited recovery thereafter (P > 0.05; P = 0.00008). Hepatic analysis revealed elevated levels of TNF-α (P < 0.0001), IL-6 (P = 0.005), and NF-κB (P = 0.41), alongside a significant reduction in IFN-γ (P < 0.001) expression in the morphine group compared to controls. After withdrawal, TNF-α (P < 0.01) and IFN-γ (P = 0.004) levels decreased, while NF-κB (P = 0.03) and IL-6 (P = 0.4(remained elevated, indicating persistent inflammatory responses. CONCLUSION: Morphine causes lasting gut dysbiosis and liver inflammation, indicating disruption of the gut-liver axis in opioid dependence. These results emphasize morphine’s impact on gut microbiota and liver health, suggesting significant long-term effects of opioid use. Targeting microbiota modulation and anti-inflammatory approaches may offer therapeutic options for opioid-related conditions.