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Role of the gut-brain axis in HIV and drug abuse-mediated neuroinflammation
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Drug abuse and related disorders are a global public health crisis affecting millions, but to date, limited treatment options are available. Abused drugs include but are not limited to opioids, cocaine, nicotine, methamphetamine, and alcohol. Drug abuse and human immunodeficiency virus-1/acquired immune deficiency syndrome (HIV-1/AIDS) are inextricably linked. Extensive research has been done to understand the effect of prolonged drug use on neuronal signaling networks and gut microbiota. Recently, there has been rising interest in exploring the interactions between the central nervous system and the gut microbiome. This review summarizes the existing research that points toward the potential role of the gut microbiome in the pathogenesis of HIV-1-linked drug abuse and subsequent neuroinflammation and neurodegenerative disorders. Preclinical data about gut dysbiosis as a consequence of drug abuse in the context of HIV-1 has been discussed in detail, along with its implications in various neurodegenerative disorders. Understanding this interplay will help elucidate the etiology and progression of drug abuse-induced neurodegenerative disorders. This will consequently be beneficial in developing possible interventions and therapeutic options for these drug abuse-related disorders.
Cocaine is a potent vasoconstrictor and brain stimulant. Its abuse leads to severe neurological (fainting attacks, hemorrhagic brain strokes, CNS vasculitis, and encephalopathies), cardiovascular (cardiac arrhythmia and heart attacks), and gastrointestinal complications (112-117). Cocaine abuse has been reported to alter the gut microbiota composition which in turn affects the uptake and clearence of neurotransmitters.
OPIOIDS
Disruption of the gut epithelium, in turn, allows bacteria and their toxic products to enter the host circulatory system, subsequently activating several inflammatory pathways and neuroinflammation.
Opioids have also been reported to promote HIV-1 disease progression by disrupting the intestinal epithelial self-repair mechanism and reducing epithelial proliferation in bone marrow-liver-thymus humanized mice and in opioid-using HIV-1+ patients (75). Cumulatively these studies underscore the pivotal role of gut microbiota in the disease progression of HIV-1 infection while also demonstrating that opioid abuse by HIV-1 patients can lead to severe disruption of gut homeostasis, resulting in an accelerated progression of the disease in comparison to drug naïve, infected individuals.
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