Researchers report a role for the gut microbiome in morphine tolerance. Opioid use in the United States has risen significantly over the past decade, leading to the development of opioid analgesic tolerance in a subset of the population and reducing the effectiveness of opioids for chronic pain treatment. Using mouse models, Sabita Roy and colleagues explored the role of gut microbiota in the development of morphine tolerance. Mice treated with repeated escalating doses of morphine for 8 days developed analgesic tolerance to morphine. However, compared with control mice, tolerance was significantly lower in germ-free (GF) mice, which never develop microbiota, or in mice treated with antibiotics to deplete their microbiota. When the microbiota of GF and antibiotic-treated mice were restored via fecal microbial transplantation from control mice prior to morphine treatment, both types of mice developed morphine tolerance. Bacterial communities in the microbiota differed significantly between morphine-tolerant and control mice, with tolerant mice being depleted in Bifidobacteria and Lactobacillaeae. Treatment with probiotics restored the depleted microbial communities, and mice pretreated with probiotics developed significantly reduced morphine tolerance compared with controls. The results indicate a role for the gut microbiota in morphine tolerance and suggest that probiotic pretreatment could prevent the development of morphine tolerance and prolong the efficacy of morphine for pain management, according to the authors.
Article #19-01182: "Morphine tolerance is attenuated in germ-free mice and reversed by probiotics, implicating the role of gut microbiome," by Li Zhang et al.
MEDIA CONTACT: Sabita Roy, University of Miami, FL; tel: 305-243-8452; e-mail: Sabita.roy@miami.edu
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Proceedings of the National Academy of Sciences