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Published on: May 2, 2018
Opioid-induced gut microbial disruption and bile dysregulation leads to gut barrier compromise and sustained systemic
S Banerjee1, G Sindberg2, F Wang2
1Department of Surgery and Pharmacology, Division of Infection, Inflammation and Vascular Biology, University of Minnesota, Minneapolis, Minnesota, USA.
Abstract:
Morphine and its pharmacological derivatives are the most prescribed analgesics for moderate to severe pain management. However, chronic use of morphine reduces pathogen clearance and induces bacterial translocation across the gut barrier. The enteric microbiome has been shown to have a critical role in the preservation of the mucosal barrier function and metabolic homeostasis. Here, we show for the first time, using bacterial 16s rDNA sequencing, that chronic morphine treatment significantly alters the gut microbial composition and induces preferential expansion of Gram-positive pathogenic and reduction in bile-deconjugating bacterial strains. A significant reduction in both primary and secondary bile acid levels was seen in the gut, but not in the liver with morphine treatment. Morphine-induced microbial dysbiosis and gut barrier disruption was rescued by transplanting placebo-treated microbiota into morphine-treated animals, indicating that microbiome modulation could be exploited as a therapeutic strategy for patients using morphine for pain management.
Insights
Chronic morphine use disrupts the gut microbiome, increasing pathogens and reducing beneficial bacteria. Restoring healthy gut bacteria can reverse these harmful effects, offering a new therapeutic avenue.
Area of Science:
- Microbiology
- Pharmacology
- Gastroenterology
Background:
- Morphine is a primary analgesic for severe pain.
- Chronic morphine use impairs pathogen clearance and gut barrier integrity.
- The enteric microbiome is crucial for mucosal barrier function and homeostasis.
Purpose of the Study:
- To investigate the impact of chronic morphine on gut microbial composition.
- To determine the effect of morphine on bile acid metabolism.
- To explore microbiome modulation as a therapeutic strategy for morphine-induced gut issues.
Main Methods:
- Bacterial 16S rDNA sequencing was used to analyze gut microbial composition.
- Bile acid levels were measured in the gut and liver.
- Fecal microbiota transplantation was performed to assess therapeutic potential.
Main Results:
- Chronic morphine treatment significantly altered gut microbial composition.
- Morphine induced expansion of Gram-positive pathogens and reduced bile-deconjugating bacteria.
- A significant reduction in gut bile acid levels was observed, but not in the liver.
- Microbiome transplantation reversed morphine-induced dysbiosis and gut barrier disruption.
Conclusions:
- Chronic morphine use causes significant gut dysbiosis and barrier disruption.
- Microbiome modulation presents a potential therapeutic strategy for managing morphine-induced side effects.
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