A review of potential microbiome-gut-brain axis mediated neurocognitive conditions in persons living with HIV

Abstract

The microbiome-gut-brain axis, or the various interactions between the gut microbiome and the brain, has been of recent interest in the context of precision medicine research for a variety of disease states. Persons living with human immunodeficiency virus (PLWH) experience higher degrees of neurocognitive decline than the general population, correlating with a disruption of the normal gut microbiome composition (i.e. dysbiosis). While the nature of this correlation remains to be determined, there is the potential that the microbiome-gut-brain axis contributes to the progression of this disease. Previous research has established that the pathology associated with HIV induces alterations in the composition of gut microbiome, including a shift from Bacteroides to Prevotella dominance, and compromises gut barrier integrity, which may promote microbial translocation and consequent systemic inflammation and exacerbation of neuroinflammation. Further, though the use of antiretroviral therapy has been found to partially counteract HIV-related dysbiosis, it may also induce its own dysbiosis patterns, presenting a unique challenge for this research. More recent research has suggested the gut microbiome as a target for therapeutic interventions to improve symptoms associated with a variety of disease states, including HIV. Early findings are promising and warrant further research regarding the gut microbiome as a potential modifiable factor to improve health outcomes for PLWH. This review will discuss the current knowledge concerning the neuropathogenesis of HIV in the brain, role of the gut microbiome in neuroinflammation, and the relationship between HIV-status and the gut microbiome, followed by a conclusion that synthesizes this information within the context of the microbiome-gut-brain axis among PLWH. This review will also highlight the limitations of existing studies and propose future directions of this research.

Microbiome-Related Indole and Serotonin Metabolites are Linked to Inflammation and Psychiatric Symptoms in People Living with HIV

“… 39 Altogether, these findings suggest a protective role of tryptophan, plasma metabolites of serotonin, and indoles on psychiatric symptoms in PLHIV, while kynurenine metabolites showed an opposite effect. Our findings also corroborate previous reports of a disturbance of the microbiome-gut-brain axis in PLHIV (reviewed by 76 ).…”

Developments in Neuroprotection for HIV-Associated Neurocognitive Disorders (HAND)

“…Nonetheless, it should be considered [62]. Also, therapies targeted towards directly reducing microbial translocation (e.g., preserving gut mucosal integrity) in PLWH may have a role in neuroprotection, although no such specific therapies currently exist [67]. Focusing on correcting the gut microbiome dysbiosis as a means of promoting gut integrity and additionally reducing systemic inflammation is a reasonable strategy for attempting to reduce HIV-NCI risk; indeed, preliminary evidence suggests that probiotic dietary supplementation may reduce neuroinflammation and promote neurocognitive recovery in PLWH [67][68][69].…”

Through the Looking-Glass: Psychoneuroimmunology and the Microbiome-Gut-Brain Axis in the Modern Antiretroviral Therapy Era

“…In PWH, markers of microbial translocation (e.g., LPS), monocyte activation, changes in gut microbiota composition (e.g., alteration in the ratio of Firmicutes to Bacteroides), and heightened IDO-1 activity have been associated with cognitive impairment and morphological brain changes (103)(104)(105)(106)(107). An extensive review of microbiome-gut-brain axis mechanisms relevant to cognitive impairment among PWH has been published elsewhere (43).…”

“…PWH show a decrease in bacterial production of neuroprotective short-chain fatty acids and other neuroactive metabolites, as well as concomitant increases in tryptophan catabolism, immune activation, and inflammation secondary to microbial translocation as noted previously ( 42 , 89 , 99 – 102 ). These mechanisms can potentiate the production of neurotoxic metabolites, increase permeability of the blood-brain barrier, and stimulate immune cells to transport HIV across the blood-brain barrier ( 43 , 103 , 104 ). In PWH, markers of microbial translocation (e.g., LPS), monocyte activation, changes in gut microbiota composition (e.g., alteration in the ratio of Firmicutes to Bacteroides ), and heightened IDO-1 activity have been associated with cognitive impairment and morphological brain changes ( 103 – 107 ).…”