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GUT MICROBIOTA

Gastrointestinal motility, dysbiosis and opioid-induced tolerance: is there a link?

Studies show that gut microbial dysbiosis induced by chronic opioid use is linked to central opioid tolerance. Here, we suggest that a persistent decrease in gastrointestinal motility by opioids is a primary cause of gut microbial dysbiosis and that improving gastrointestinal transit might be a strategy in preventing opioid analgesic tolerance.

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Fig. 1: Antinociceptive tolerance to opioids through changes in the gut microbiota.

References

  1. Scriven, M. et al. Neuropsychiatric disorders: influence of gut microbe to brain signalling. Diseases 6, 78 (2018).

    Article  Google Scholar 

  2. Bell, T. J. et al. The prevalence, severity, and impact of opioid-induced bowel dysfunction: results of a US and European Patient Survey (PROBE 1). Pain Med. 10, 35–42 (2009).

    Article  Google Scholar 

  3. Touw, K. et al. Mutual reinforcement of pathophysiological host-microbe interactions in intestinal stasis models. Physiol. Rep. 5, e13182 (2017).

    Article  Google Scholar 

  4. Xu, Y. et al. Bacterial diversity of intestinal microbiota in patients with substance use disorders revealed by 16S rRNA gene deep sequencing. Sci. Rep. 7, 3628 (2017).

    Article  Google Scholar 

  5. Acharya, C. et al. Chronic opioid use is associated with altered gut microbiota and predicts readmissions in patients with cirrhosis. Aliment. Pharmacol. Ther. 45, 319–331 (2017).

    Article  CAS  Google Scholar 

  6. Barengolts, E. et al. Gut microbiota varies by opioid use, circulating leptin and oxytocin in African American men with diabetes and high burden of chronic disease. PLOS ONE 13, e0194171 (2018).

    Article  Google Scholar 

  7. Lichtenstein, G. R. et al. Serious infection and mortality in patients with Crohn’s disease: more than 5 years of follow-up in the TREAT registry. Am. J. Gastroenterol. 107, 1409–1422 (2012).

    Article  CAS  Google Scholar 

  8. Akbarali, H. I. & Dewey, W. L. The gut-brain interaction in opioid tolerance. Curr. Opin. Pharmacol. 37, 126–130 (2017).

    Article  CAS  Google Scholar 

  9. Mischel, R. A., Dewey, W. L. & Akbarali, H. I. Tolerance to morphine-induced inhibition of TTX-R sodium channels in dorsal root ganglia neurons is modulated by gut-derived mediators. iScience 2, 193–209 (2018).

    Article  CAS  Google Scholar 

  10. Hutchinson, M. R. et al. Exploring the neuroimmunopharmacology of opioids: an integrative review of mechanisms of central immune signaling and their implications for opioid analgesia. Pharmacol. Rev. 63, 772–810 (2011).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by National Institutes of Health grant DA036975.

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Correspondence to Hamid I. Akbarali.

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Centers for Disease Control and Prevention (CDC) WONDER: https://wonder.cdc.gov

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Akbarali, H.I., Dewey, W.L. Gastrointestinal motility, dysbiosis and opioid-induced tolerance: is there a link?. Nat Rev Gastroenterol Hepatol 16, 323–324 (2019). https://doi.org/10.1038/s41575-019-0150-x

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