Morphine induces bacterial translocation in mice by compromising intestinal barrier function in a TLR-dependent manner
Open accessAbstract
Opiates are among the most prescribed drugs for pain management. However, morphine use or abuse results in significant gut bacterial translocation and predisposes patients to serious infections with gut origin. The mechanism underlying this defect is still unknown. In this report, we investigated the mechanisms underlying compromised gut immune function and bacterial translocation following morphine treatment. We demonstrate significant bacterial translocation to mesenteric lymph node (MLN) and liver following morphine treatment in wild-type (WT) animals that was dramatically and significantly attenuated in Toll-like receptor (TLR2 and 4) knockout mice. We further observed significant disruption of tight junction protein organization only in the ileum but not in the colon of morphine treated WT animals. Inhibition of myosin light chain kinase (MLCK) blocked the effects of both morphine and TLR ligands, suggesting the role of MLCK in tight junction modulation by TLR. This study conclusively demonstrates that morphine induced gut epithelial barrier dysfunction and subsequent bacteria translocation are mediated by TLR signaling and thus TLRs can be exploited as potential therapeutic targets for alleviating infections and even sepsis in morphine-using or abusing populations.
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Vitamin and mineral deficiencies associated with opioid addiction have been well-described.
“Vitamin and mineral deficiencies associated with opioid addiction have been well-described (160–165).”
From A Biopsychosocial Overview of the Opioid Crisis: Considering Nutrition and Gastrointestinal Health (2019) · cites this paper as [161]
Similar to alcohol, opioid ingestion can disrupt the intestinal epithelium leading to bacterial translocation and subsequent inflammatory cascades.
“Similar to alcohol, opioid ingestion can disrupt the intestinal epithelium (160) leading to bacterial translocation and subsequent inflammatory cascades (161).”
From A Biopsychosocial Overview of the Opioid Crisis: Considering Nutrition and Gastrointestinal Health (2019) · cites this paper as [161]
Many daily therapies and interventions in intensive care increase intestinal permeability, bacterial translocation, and bacterial virulence.
“Many daily therapies and interventions in intensive care increase intestinal permeability (eg, nonsteroidal anti-inflammatory drugs109 and parenteral feeding55,82), bacterial translocation (eg, antibiotics,65 corticosteroids,110 and opiates111), and bacterial virulence (eg, opiates19 and catecholamines22,51).”
From The microbiome and critical illness (2016) · cites this paper as [111]
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- Authors
- Meng, J., Yu, H., Ma, J., Wang, J., Banerjee, S., Charboneau, R., Barke, R. A., & Roy, S.
- Affiliations
- University of Minnesota (US)
- Minneapolis VA Medical Center (US)
- Corresponding author
- Roy, Sabita
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-01-18
- Volume
- 8
- Issue
- 1
- Pages
- e54040
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3548814
- OpenAlex
- W2016912297
- Cited by
- 212
- References
- 42
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 21 · 2023: 15 · 2022: 37 · 2021: 21 · 2020: 21 · 2019: 19 · 2018: 14 · 2017: 8 · 2016: 10 · 2015: 11 · 2014: 5
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- U.S. Department of Veterans Affairs
- University of Minnesota
- National Institutes of Health
- National Institute on Drug Abuse (K05DA033881, P50 DA 11806, P50DA011806, R01DA022935, R01DA031202, R01DA12104, KO2DA15349, R01DA034582, R01DA012104, K02DA015349)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- morphine, bacterial translocation, intestinal barrier dysfunction, TLR2, TLR4, tight junctions, myosin light chain kinase, mesenteric lymph nodes, sepsis, intestinal epithelium
- MeSH terms
- Analgesics, Opioid, Animals, Azepines, Cell Line, Colon, Epithelium, Ileum, Intestinal Mucosa, Intestines, Liver, Lymph Nodes, Mesentery, Mice, Inbred C57BL, Microscopy, Fluorescence, Morphine, Myosin-Light-Chain Kinase, Naphthalenes, Blotting, Western, Receptors, Opioid, mu, Mice, Knockout, Bacterial Translocation, Tight Junctions, Reverse Transcriptase Polymerase Chain Reaction, Toll-Like Receptor 2, Toll-Like Receptor 4, Mice, Zonula Occludens-1 Protein
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