Opioid Use May Contribute to Imbalances in the Gut and Spur Inflammation, Studies Find

Extended use of opioids promotes imbalances in the gut microbiome and triggers changes that worsen inflammation in the intestine, according to results of studies in a mouse model of colitis and tissue samples from Crohn’s disease patients.

The results were shared recently in an abstract, “Prescription opioids induce gut dysbiosis and exacerbate inflammatory bowel disease,” published in Gastroenterology.

Hydromorphone (sold under the brand name Dilaudid, among others) is the most common opioid prescribed for patients with moderate-to-severe pain due to inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD).

The potential side effects of continuous use of opioids in IBD patients remains largely unknown, although some studies suggest that its long-term use is linked to increased complications and hospitalizations, contributing to decreased quality of life.

“We hypothesized that hydromorphone can worsen intestinal inflammation,” researchers wrote. To test this theory they examined the effects of hydromorphone on a mouse model of colitis (inflammation in the colon), the so-called dextran sodium sulfate (DSS)-induced colitis mouse model, and compared it to control (non-inflammed) mice.

The animals first received hydromorphone and the colitis group was then submitted to treatment with DSS for five days to induce colitis.

They looked specifically at how the colitis impacted the gut microbiome, the natural community of microorganisms living in the gut and increasingly recognized to play vital roles in maintaining good health.

DSS-induced colitis, as expected, induced an imbalance of the gut microbiome, with impairments in the gut barrier.

Treatment with hydromorphone alone led to the same negative effects, and inflammation and disease severity were worse when the animals received both hydromorphone and DSS.

Researchers also measured the level of inflammation in the intestines of IBD patients undergoing regular treatment with opioids and compared it to that of untreated patients.

Analysis of intestine tissue samples from Crohn’s disease patients taking opioids showed several changes in the intestines’ architecture — erosion of epithelial cells, ulcers and edema — and signs of increased inflammation compared to non-opioid using patients. These changes were similar to that observed in the hydromorphone-treated DSS mice.

Overall, “our findings indicate that hydromorphone use increases intestinal inflammation and dysbiosis. We found an association between opioid use and intestinal inflammation in Crohn’s disease patients,” researchers wrote.

“These findings warrant a careful evaluation of the potential detrimental effects of opioids on intestinal inflammation in patients with IBD and should be prescribed cautiously,” they concluded.