Prescription opioid induce gut dysbiosis and exacerbate colitis in a murine model of Inflammatory Bowel Disease.
J Crohns Colitis. 2019 Nov 27;:
Authors: Sharma U, Olson RK, Erhart FN, Zhang L, Meng J, Segura B, Banerjee S, Sharma M, Saluja AK, Ramakrishnan S, Abreu MT, Roy S
BACKGROUND AND AIMS: Opioids are the most prescribed analgesics for pain in Inflammatory Bowel Diseases (IBD), however the consequences of opioid use on IBD severity is not well defined. This is the first study investigating consequences of hydromorphone in both dextran sodium sulfate (DSS)-induced colitis and spontaneous colitis [IL-10 knockout (IL-10-/-)] mouse model of IBD.
METHODS: To determine the consequences of opioid on IBD pathogenesis, wild-type (WT) mice were treated with clinically relevant dose of hydromorphone and colitis was induced via 3% DSS in drinking water for 5 days. In parallel we also determined the consequences of opioid in a spontaneous colitis model.
RESULTS: Hydromorphone and DSS independently induced barrier dysfunction, bacterial translocation, disruption of tight junction organization, and increased intestinal and systemic inflammation, which were exacerbated in mice receiving hydromorphone in combination with DSS. Hydromorphone plus DSS treated mice exhibited significant microbial dysbiosis. Predictive metagenomic analysis of the gut microbiota revealed high abundance in the bacterial communities associated with virulence, antibiotic resistance, toxin production and inflammatory properties. Hydromorphone modulates tight junction organization in a myosin light chain kinase (MLCK)-dependent manner. Treatment with ML-7 ameliorates the detrimental effects of hydromorphone on DSS induced colitis, thus decrease severity of IBD. Similarly, we demonstrated that hydromorphone treatment in IL-10/- mice resulted in accelerated clinical manifestations of colitis compared to control mice.
CONCLUSIONS: Opioid used for pain management in IBD accelerate IBD progression by dysregulation of the gut microbiota leading to expansion of pathogenic bacteria, translocation of bacteria, immune deregulation, and sustained inflammation.
PMID: 31773170 [PubMed – as supplied by publisher]