The role of morphine‐ and fentanyl‐induced impairment of intestinal epithelial antibacterial activity in dysbiosis and its impact on the microbiota‐gut‐brain axis

• DOI: 10.1096/fj.202301590rr
• Publication Date: 2024-04-22T18:30:25Z
• Authors: Karan H. Muchhala; Prajkta S. Kallurkar; Minho Kang; Eda Koseli; Justin L. Poklis; Qingguo Xu; William L. Dewey; Jennifer M. Fettweis; Nicole R. Jimenez; Hamid I. Akbarali
• Keywords: Dysbiosis; Gut–brain axis

Recent evidence suggests that chronic exposure to opioid analgesics such as morphine disrupts the intestinal epithelial layer and causes dysbiosis. Depleting gut bacteria can preclude development of tolerance opioid-induced antinociception, suggesting an important role gut-brain axis in mediating effects. The mechanism underlying dysbiosis, however, remains unclear. Host-produced antimicrobial peptides (AMPs) are critical for integrity barrier they prevent pathogenesis enteric microbiota. Here, we report or fentanyl reduces activity ileum, resulting changes composition bacteria. Fecal samples from morphine-treated mice had increased levels Akkermansia muciniphila with a shift abundance ratio Firmicutes Bacteroidetes. microbial transplant (FMT) morphine-naïve oral supplementation butyrate restored (a) activity, (b) expression peptide, Reg3γ, (c) prevented increase permeability (d) antinociceptive morphine-dependent mice. Improved function FMT enrichment mucin-degrading A. These data implicate impairment epithelium by which opioids disrupt microbiota-gut-brain axis.