Researchers Find Probiotics Can Reduce Morphine Tolerance in Mice

A group of researchers from Sylvester Comprehensive Cancer Center, the Department of Surgery and the Department of Medicine at the University of Miami Miller School of Medicine have found that probiotics can reduce morphine tolerance when used as an adjunct therapy in germ-free mice.

Their findings, recently published in the Proceedings of the National Academy of Sciences, provide new evidence of a strong role played by the gut microbiome during treatment with opioid painkillers.

“More than 11 percent of American adults suffer from chronic pain, and nearly 18 percent experience more severe pain,” said Sabita Roy, Ph.D., a Sylvester member and professor of surgery, who was the paper’s senior author. “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.”

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 rich in Bifidobacteria and Lactobacillaceae, morphine-induced tolerance was significantly reduced.

“This is the first study that unequivocally demonstrates that the gut microbiome contributes to morphine tolerance,” Dr. Roy said. “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 funding source for the study was the National Institute of Drug Abuse.

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