Morphine induces changes in the gut microbiome and metabolome in a morphine dependence model
Open accessAbstract
Opioid analgesics are frequently prescribed in the United States and worldwide. However, serious comorbidities, such as dependence, tolerance, immunosuppression and gastrointestinal disorders limit their long-term use. In the current study, a morphine-murine model was used to investigate the role of the gut microbiome and metabolome as a potential mechanism contributing to the negative consequences associated with opioid use. Results reveal a significant shift in the gut microbiome and metabolome within one day following morphine treatment compared to that observed after placebo. Morphine-induced gut microbial dysbiosis exhibited distinct characteristic signatures, including significant increase in communities associated with pathogenic function, decrease in communities associated with stress tolerance and significant impairment in bile acids and morphine-3-glucuronide/morphine biotransformation in the gut. Moreover, expansion of Enterococcus faecalis was strongly correlated with gut dysbiosis following morphine treatment, and alterations in deoxycholic acid (DCA) and phosphatidylethanolamines (PEs) were associated with opioid-induced metabolomic changes. Collectively, these results indicate that morphine induced distinct alterations in the gut microbiome and metabolome, contributing to negative consequences associated with opioid use. Therapeutics directed at maintaining microbiome homeostasis during opioid use may reduce the comorbidities associated with opioid use for pain management.
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These findings have been replicated, and certain microbial communities associated with stress tolerance are reduced in the morphine-rodent model.
“These findings have been replicated, and it has been added that certain microbial communities associated with stress tolerance are reduced in the morphine-rodent model (181).”
From A Biopsychosocial Overview of the Opioid Crisis: Considering Nutrition and Gastrointestinal Health (2019) · cites this paper as [181]
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- Authors
- Wang, F., Meng, J., Zhang, L., Johnson, T., Chen, C., & Roy, S.
- Affiliations
- University of Minnesota (US)
- University of Miami (US)
- Corresponding author
- Roy, Sabita
- Venue
- Scientific Reports
- Published
- 2018-02-26
- Volume
- 8
- Issue
- 1
- Pages
- 3596-3596
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5827657
- OpenAlex
- W2805365360
- Cited by
- 238
- References
- 61
- Citations by year
- 2026: 11 · 2025: 27 · 2024: 30 · 2023: 40 · 2022: 41 · 2021: 33 · 2020: 31 · 2019: 14 · 2018: 10
- FWCI
- 7.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (R01DA044582, R01DA037843, R01DA043252, R01DA047089)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Keywords
- morphine, opioid use disorder, gut microbiota, gut metabolome, dysbiosis, Enterococcus faecalis, deoxycholic acid, phosphatidylethanolamine, bile acids, morphine-3-glucuronide, stress tolerance, pain management
- MeSH terms
- Gastrointestinal Microbiome, Analgesics, Opioid, Analysis of Variance, Animals, Deoxycholic Acid, Disease Models, Animal, Drug Tolerance, Female, Mice, Inbred C57BL, Morphine, Morphine Dependence, Morphine Derivatives, Naltrexone, Narcotic Antagonists, Phosphatidylethanolamines, Enterococcus faecalis, Statistics, Nonparametric, Mice, Metabolome, Dysbiosis
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