Opioid use potentiates the virulence of hospital-acquired infection, increases systemic bacterial dissemination and exacerbates gut dysbiosis in a murine model of Citrobacter rodentium infection

Fuyuan Wang, Jingjing Meng, Li Zhang, Sabita Roy

Research output: Contribution to journalArticle

Abstract

Opioid analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit their use. It was recently demonstrated that morphine treatment results in a significant disruption in gut barrier function, leading to an increased translocation of gut commensal bacteria. Further studies have indicated distinct alterations in the gut microbiome and metabolome following morphine treatment, contributing to the negative consequences that are associated with opioid use. However, it is unclear how opioids modulate gut homeostasis in the context of a hospital-acquired bacterial infection. Citrobacter rodentium is an ideal murine model of human infections with enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC). In the current study, a mouse model of C. rodentium infection was used to investigate the role of morphine in the modulation of gut homeostasis in the context of a hospital-acquired bacterial infection. Morphine treatment resulted in 1) the promotion of C. rodentium systemic dissemination, 2) an increase in the expression of the virulence factors of C. rodentium colonization in intestinal contents, 3) altered gut microbiome, 4) damaged integrity of gut epithelial barrier function, 5) inhibition of the C. rodentium-induced increase in goblet cells, and 6) dysregulated IL-17A immune response. This study demonstrates and further validates a positive correlation between opioid drug use/abuse and an increased risk of infections, suggesting that the overprescription of opioids may increase the susceptibility to hospital-acquired infection.

Original languageEnglish (US)
JournalGut Microbes
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Citrobacter rodentium
Dysbiosis
Cross Infection
Opioid Analgesics
Virulence
Morphine
Infection
Bacterial Infections
Homeostasis
Enterohemorrhagic Escherichia coli
Enteropathogenic Escherichia coli
Gastrointestinal Contents
Goblet Cells
Metabolome
Interleukin-17
Virulence Factors
Immunosuppression
Substance-Related Disorders
Therapeutics
Bacteria

Keywords

  • bacterial infection
  • citrobacter rodentium
  • Gut dysbiosis
  • Opioid-related disorders

ASJC Scopus subject areas

  • Microbiology
  • Gastroenterology
  • Microbiology (medical)
  • Infectious Diseases

Cite this

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title = "Opioid use potentiates the virulence of hospital-acquired infection, increases systemic bacterial dissemination and exacerbates gut dysbiosis in a murine model of Citrobacter rodentium infection",
abstract = "Opioid analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit their use. It was recently demonstrated that morphine treatment results in a significant disruption in gut barrier function, leading to an increased translocation of gut commensal bacteria. Further studies have indicated distinct alterations in the gut microbiome and metabolome following morphine treatment, contributing to the negative consequences that are associated with opioid use. However, it is unclear how opioids modulate gut homeostasis in the context of a hospital-acquired bacterial infection. Citrobacter rodentium is an ideal murine model of human infections with enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC). In the current study, a mouse model of C. rodentium infection was used to investigate the role of morphine in the modulation of gut homeostasis in the context of a hospital-acquired bacterial infection. Morphine treatment resulted in 1) the promotion of C. rodentium systemic dissemination, 2) an increase in the expression of the virulence factors of C. rodentium colonization in intestinal contents, 3) altered gut microbiome, 4) damaged integrity of gut epithelial barrier function, 5) inhibition of the C. rodentium-induced increase in goblet cells, and 6) dysregulated IL-17A immune response. This study demonstrates and further validates a positive correlation between opioid drug use/abuse and an increased risk of infections, suggesting that the overprescription of opioids may increase the susceptibility to hospital-acquired infection.",
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AU - Zhang, Li

AU - Roy, Sabita

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