Opioid-induced gut microbial disruption and bile dysregulation leads to gut barrier compromise and sustained systemic inflammation

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 play 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 Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use

Drug Use is Associated with Anti-CD4 IgG-mediated CD4+ T Cell Death and Poor CD4+ T Cell Recovery in Viral-suppressive HIV-infected Individuals Under Antiretroviral Therapy

“…Illicit drugs have been shown to associate with increased systemic inflammation [59, 60], which may result from cellular activation and oxidative stress [61, 62], and induction of gut microbial translocation [21, 22, 63, 64]. Studies from our group and others indicate that HIV infection is associated with a permeable gut, increased microbial translocation, and increased CD4+ T cell apoptosis and inflammation [11, 65-67].…”

“…Drug use has shown to associate with increased inflammation [21, 22]. HIV infected drug users experience neurocognitive dysfunction mediated by increased systemic and local inflammation, as well as accelerated HIV disease progression [23-27].…”

Gut microbiome, surgical complications and probiotics

“…Moreover, P. aeruginosa possesses the ability to switch phenotype from being mucus-enhancing to mucus-suppressing - having the ability to destroy gut epithelial integrity - depending on the presence or absence of morphine [43]. Additionally, Banerjee et al [44] have very recently shown for the first time that chronic morphine treatment significantly alters the gut microbiome composition and induces a preferential expansion of Gram-positive as well as a reduction in bile-deconjugating bacterial strains.…”

The role of the microbiota in surgical recovery

“…(12) Lastly, opioids such as morphine and its derivatives, which are used almost ubiquitously to control post-operative pain, have a profound impact on the composition and function of the intestinal microbiome. (13) In addition, systemic morphine exposure compromises the intestinal barrier function leading to bacterial translocation and a pro-inflammatory phenotype, which can be transferred through the route of fecal microbiota transplant (FMT) to mice naïve to morphine. Banerjee et al further corroborate that morphine effect is mediated by the intestinal microbiota through the restoration of gut immune homeostasis with FMT from healthy placebo-treated mice transferred into those treated with morphine.…”

“…Banerjee et al further corroborate that morphine effect is mediated by the intestinal microbiota through the restoration of gut immune homeostasis with FMT from healthy placebo-treated mice transferred into those treated with morphine. (13) Our lab has previously demonstrated that systemic morphine administration has a potential to transform pathogenic bacteria into a more virulent phenotype. (14–16) In this work, intestinal Pseudomonas aeruginosa inoculation following laparotomy (with or without partial hepatectomy) in mice implanted with subcutaneous morphine pellet led to enhanced virulence and shift to a lethal phenotype.…”