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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\n Lactobacillus<\/jats:italic>\n ,\n Bifidobacterium<\/jats:italic>\n ,\n Clostridium<\/jats:italic>\n ,\n Bacteroides<\/jats:italic>\n , and\n Faecalibacterium<\/jats:italic>\n . Liver tissues were examined for inflammatory markers (\n TNF-\u03b1<\/jats:italic>\n ,\n IFN-\u03b3<\/jats:italic>\n ,\n IL-6<\/jats:italic>\n ,\n NF-\u03baB<\/jats:italic>\n ) using RT-qPCR after treatment and withdrawal.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A significant decline in\n Lactobacillus<\/jats:italic>\n (\n P<\/jats:italic>\n \u2009=\u20090.011) and\n Bifidobacterium<\/jats:italic>\n (\n P<\/jats:italic>\n \u2009=\u20090.003) following morphine treatment, with partial recovery observed after withdrawal (\n P<\/jats:italic>\n \u2009=\u20090.014;\n P<\/jats:italic>\n \u2009=\u20090.0009), yet levels remained below baseline. Conversely,\n Clostridium<\/jats:italic>\n levels increased significantly during treatment (\n P<\/jats:italic>\n \u2009=\u20090.0001), persisting at elevated levels post-withdrawal (\n P<\/jats:italic>\n \u2009=\u20090.0001).\n Bacteroides<\/jats:italic>\n and\n Faecalibacterium<\/jats:italic>\n also exhibited decreased abundances during morphine treatment (\n P<\/jats:italic>\n \u2009>\u20090.05;\n P<\/jats:italic>\n \u2009=\u20090.00009), with limited recovery thereafter (\n P<\/jats:italic>\n \u2009>\u20090.05;\n P<\/jats:italic>\n \u2009=\u20090.00008). Hepatic analysis revealed elevated levels of\n TNF-\u03b1<\/jats:italic>\n (\n P<\/jats:italic>\n \u2009<\u20090.0001),\n IL-6<\/jats:italic>\n (\n P\u2009=<\/jats:italic>\n \u20090.005), and\n NF-\u03baB<\/jats:italic>\n (\n P\u2009=<\/jats:italic>\n \u20090.41), alongside a significant reduction in\n IFN-\u03b3<\/jats:italic>\n (\n P<\/jats:italic>\n \u2009<\u20090.001) expression in the morphine group compared to controls. After withdrawal,\n TNF-\u03b1<\/jats:italic>\n (\n P<\/jats:italic>\n \u2009<\u20090.01) and\n IFN-\u03b3<\/jats:italic>\n (\n P<\/jats:italic>\n \u2009=\u20090.004) levels decreased, while\n NF-\u03baB<\/jats:italic>\n (\n P<\/jats:italic>\n \u2009=\u20090.03) and\n IL-6<\/jats:italic>\n (\n P\u2009=<\/jats:italic>\n \u20090.4(remained elevated, indicating persistent inflammatory responses.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Morphine causes lasting gut dysbiosis and liver inflammation, indicating disruption of the gut-liver axis in opioid dependence. These results emphasize morphine\u2019s 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.<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s12876-026-04669-w","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T03:35:14Z","timestamp":1770608114000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gut microbiota dysbiosis and hepatic inflammation in morphine dependence and withdrawal: insights from a rat model"],"prefix":"10.1186","volume":"26","author":[{"given":"Shirin","family":"Yousefi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Sadeghi-Adl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Tarashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Davar","family":"Siadat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"issue":"1","key":"4669_CR1","doi-asserted-by":"publisher","first-page":"2348","DOI":"10.25215\/0501.057","volume":"5","author":"J Singh","year":"2017","unstructured":"Singh J, Gupta PK. 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