Prolonged exposure to opioids results in analgesic tolerance, drug overdose, and death. The mechanism underlying morphine analgesic tolerance remains unresolved.
In a new study by the scientists from Sylvester Comprehensive Cancer Center, the Department of Surgery and the Department of Medicine at the University of Miami Miller School of Medicine have discovered that probiotics can diminish morphine tolerance when utilized as an adjunct therapy in germ-free mice. The study additionally shows that an active role played by the gut microbiome during treatment with opioid painkillers.
Using germ-free mice and antibiotic depletion strategies, the researchers showed that opioid tolerance is associated with a disrupted gut microbiome involving a reduction in key microbial communities that are essential for maintaining a healthy gut. When the study animals were treated with probiotics abundant in Bifidobacteria and Lactobacillaceae, morphine-induced tolerance was significantly reduced.
Sabita Roy, Ph.D., a Sylvester member, and professor of surgery, who was the paper’s senior author said, “More than 11 percent of American adults suffer from chronic pain and nearly 18 percent experience more severe pain. Opioids are the gold standard for pain management.”
“However, prolonged use results in opioid tolerance, requiring higher doses to achieve the same level of pain management. Opioid addiction and opioid-associated deaths are a consequence of opioid tolerance. The use and over-prescription of opioids have contributed to an opioid epidemic in the U.S. that kills almost 130 people every day.”
“This is the first study that unequivocally demonstrates that the gut microbiome contributes to morphine tolerance. These results suggest that probiotic therapy during morphine administration may be a promising, safe, and inexpensive treatment to prolong morphine’s efficacy and attenuate analgesic tolerance.”
The next step will be to apply these findings in a clinical trial with human subjects.
Other Miller School authors were first author Li Zhang, M.S., Jingjing Meng, Ph.D., Yuguang Ban, Ph.D., Richa Jalodia, Ph.D., Irina Chupikova, Ph.D., Irina Fernandez, M.S., Nivis Brito, Umakant Sharma, Ph.D., Maria T. Abreu, M.D., and Sundaram Ramakrishnan. Ph.D.
The study is published in the journal Proceedings of the National Academy of Sciences.