Role of the gut-brain axis in HIV and drug abuse-mediated neuroinflammation

Abstract

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.

Chronic Morphine Treatment and Antiretroviral Therapy Exacerbate HIV-Distal Sensory Peripheral Neuropathy and Induce Distinct Microbial Alterations in the HIV Tg26 Mouse Model

“…We extended our investigation of the Tg26 mouse model to include the gut microbiome, given that opioid-induced microbial dysbiosis has been implicated in HIV-1 disease progression [43]. Our data revealed distinct differences in the bacterial communities between WT and Tg26 mice both before and after morphine treatment.…”

The Role of Gut Dysbiosis in the Loss of Intestinal Immune Cell Functions and Viral Pathogenesis

“…For instance, gut dysfunction and systemic inflammation driven by chronic HIV infection lead to neurological symptoms such as cognitive impairment, depression, and anxiety [ 124 , 126 ]. Furthermore, the development of HIV-associated neuroinflammation and cognitive impairment has been directly linked to gut dysbiosis and increased intestinal permeability [ 127 ]. It has been proposed that HIV-induced alterations in the balance of neurotransmitters in the brain contributes to disruption of the gut–brain axis, which can lead to the development of depression and other neuropsychiatric symptoms [ 128 ].…”