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Background <p>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.</p> Methods <p>Fifty male Wistar rats were separated into two groups, one received escalating morphine doses (5 to 30&#xa0;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 <i>Lactobacillus</i>, <i>Bifidobacterium</i>, <i>Clostridium</i>, <i>Bacteroides</i>, and <i>Faecalibacterium</i>. Liver tissues were examined for inflammatory markers (<i>TNF-α</i>, <i>IFN-γ</i>, <i>IL-6</i>, <i>NF-κB</i>) using RT-qPCR after treatment and withdrawal.</p> Results <p>A significant decline in <i>Lactobacillus</i> (<i>P</i> = 0.011) and <i>Bifidobacterium</i> (<i>P</i> = 0.003) following morphine treatment, with partial recovery observed after withdrawal (<i>P</i> = 0.014; <i>P</i> = 0.0009), yet levels remained below baseline. Conversely, <i>Clostridium</i> levels increased significantly during treatment (<i>P</i> = 0.0001), persisting at elevated levels post-withdrawal (<i>P</i> = 0.0001). <i>Bacteroides</i> and <i>Faecalibacterium</i> also exhibited decreased abundances during morphine treatment (<i>P</i> &gt; 0.05; <i>P</i> = 0.00009), with limited recovery thereafter (<i>P</i> &gt; 0.05; <i>P</i> = 0.00008). Hepatic analysis revealed elevated levels of <i>TNF-α</i> (<i>P</i> &lt; 0.0001), <i>IL-6</i> (<i>P =</i> 0.005), and <i>NF-κB</i> (<i>P =</i> 0.41), alongside a significant reduction in <i>IFN-γ</i> (<i>P</i> &lt; 0.001) expression in the morphine group compared to controls. After withdrawal, <i>TNF-α</i> (<i>P</i> &lt; 0.01) and <i>IFN-γ</i> (<i>P</i> = 0.004) levels decreased, while <i>NF-κB</i> (<i>P</i> = 0.03) and <i>IL-6</i> (<i>P =</i> 0.4(remained elevated, indicating persistent inflammatory responses.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月9日

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  • Shirin Yousefi,
  • Mahsa Sadeghi-Adl,
  • Samira Tarashi,
  • Seyed Davar Siadat

摘要

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.