ArticleScientific reports2015
Opioid Exacerbation of Gram-positive sepsis, induced by Gut Microbial Modulation, is Rescued by IL-17A Neutralization.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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The trial behind it
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Who cites it
76 citing papers in PubMed, 111 citations in OpenAlex.
- Dynamic flexibility of the murine gut microbiota during morphine disturbance enables escape from the stable dysbiosis that is associated with addiction-like behavior.Gut microbes · 2026Article
- Morphine-induced dysbiosis and metabolic remodeling of the gut microbiota is transmissible via fecal microbiota transplantation in mice.American journal of clinical and experimental immunology · 2026Article
- Maternal opioid use is associated with altered placental bacterial DNA and activation of immune-apoptotic pathways.NeuroImmune pharmacology and therapeutics · 2025Article
- Perinatal morphine exposure induces long-term changes in the intestinal microbiota of male and female rats.Brain, behavior, and immunity · 2025Article
- Pharmacology and Toxicology of Opioids-Recent Advances and New Perspectives.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Role of Central Inflammatory and Oxidative Pathways in the Morphine Exacerbation of Cardiovascular Effects of Sepsis in Rats.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The Bidirectional Interplay Between Substances of Abuse and Gut Microbiome Homeostasis.Life (Basel, Switzerland) · 2025Review
- Increased LPS-induced fever and sickness behavior in adult male and female rats perinatally exposed to morphine.Brain, behavior, and immunity · 2025Article
- Effects of intravenous morphine and lidocaine on bacterial growth.BMC anesthesiology · 2025Article
- Intestinal immunoglobulins under microbial dysbiosis: implications in opioid-induced microbial dysbiosis.Frontiers in microbiology · 2025Review
- Understanding the impact of the gut microbiome on opioid use disorder: Pathways, mechanisms, and treatment insights.Microbial biotechnology · 2024Review
- The Gut-Brain Axis in Opioid Use Disorder: Exploring the Bidirectional Influence of Opioids and the Gut Microbiome-A Comprehensive Review.Life (Basel, Switzerland) · 2024Review
- Opioid Use and Gut Dysbiosis in Cancer Pain Patients.International journal of molecular sciences · 2024Review
- The role of morphine- and fentanyl-induced impairment of intestinal epithelial antibacterial activity in dysbiosis and its impact on the microbiota-gut-brain axis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Review
- Blocking IL-17A prevents oxycodone-induced depression-like effects and elevation of IL-6 levels in the ventral tegmental area and reduces oxycodone-derived physical dependence in rats.Brain, behavior, and immunity · 2024Article
- The interplay between the microbiota and opioid in the treatment of neuropathic pain.Frontiers in microbiology · 2024Review
- Opioid trail: Tracking contributions to opioid use disorder from host genetics to the gut microbiome.Neuroscience and biobehavioral reviews · 2024Review
- Long access heroin self-administration significantly alters gut microbiome composition and structure.Frontiers in psychiatry · 2024Article
- Could chronic opioid use be an additional risk of hepatic damage in patients with previous liver diseases, and what is the role of microbiome?Frontiers in microbiology · 2024Review
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Sepsis is the predominant cause of mortality in ICUs, and opioids are the preferred analgesic in this setting. However, the role of opioids in sepsis progression has not been well characterized. The present study demonstrated that morphine alone altered the gut microbiome and selectively induced the translocation of Gram-positive gut bacteria in mice. Using a murine model of poly-microbial sepsis, we further demonstrated that morphine treatment led to predominantly Gram-positive bacterial dissemination. Activation of TLR2 by disseminated Gram-positive bacteria induced sustained up-regulation of IL-17A and IL-6. We subsequently showed that overexpression of IL-17A compromised intestinal epithelial barrier function, sustained bacterial dissemination and elevated systemic inflammation. IL-17A neutralization protected barrier integrity and improved survival in morphine-treated animals. We further demonstrated that TLR2 expressed on both dendritic cells and T cells play essential roles in IL-17A production. Additionally, intestinal sections from sepsis patients on opioids exhibit similar disruption in gut epithelial integrity, thus establishing the clinical relevance of this study. This is the first study to provide a mechanistic insight into the opioid exacerbation of sepsis and show that neutralization of IL-17A might be an effective therapeutic strategy to manage Gram-positive sepsis in patients on an opioid regimen.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.