Therapeutically targeting the consequences of HIV-1-associated gastrointestinal dysbiosis: Implications for neurocognitive and affective alterations

Mason T. Rodriguez; Kristen A. McLaurin; Michael Shtutman; Jason L. Kubinak; Charles F. Mactutus; Rosemarie M. Booze

doi:10.1016/j.pbb.2023.173592

Therapeutically targeting the consequences of HIV-1-associated gastrointestinal dysbiosis: Implications for neurocognitive and affective alterations

Mason T. Rodriguez, Kristen A. McLaurin, Michael Shtutman, Jason L. Kubinak, Charles F. Mactutus, Rosemarie M. Booze

Research output: Contribution to journal › Article › peer-review

Abstract

Approximately 50 % of the individuals living with human immunodeficiency virus type 1 (HIV-1) are plagued by debilitating neurocognitive impairments (NCI) and/or affective alterations. Sizeable alterations in the composition of the gut microbiome, or gastrointestinal dysbiosis, may underlie, at least in part, the NCI, apathy, and/or depression observed in this population. Herein, two interrelated aims will be critically addressed, including: 1) the evidence for, and functional implications of, gastrointestinal microbiome dysbiosis in HIV-1 seropositive individuals; and 2) the potential for therapeutically targeting the consequences of this dysbiosis for the treatment of HIV-1-associated NCI and affective alterations. First, gastrointestinal microbiome dysbiosis in HIV-1 seropositive individuals is characterized by decreased alpha (α) diversity, a decreased relative abundance of bacterial species belonging to the Bacteroidetes phylum, and geographic-specific alterations in Bacillota (formerly Firmicutes) spp. Fundamentally, changes in the relative abundance of Bacteroidetes and Bacillota spp. may underlie, at least in part, the deficits in γ-aminobutyric acid and serotonin neurotransmission, as well as prominent synaptodendritic dysfunction, observed in this population. Second, there is compelling evidence for the therapeutic utility of targeting synaptodendritic dysfunction as a method to enhance neurocognitive function and improve motivational dysregulation in HIV-1. Further research is needed to determine whether the therapeutics enhancing synaptic efficacy exert their effects by altering the gut microbiome. Taken together, understanding gastrointestinal microbiome dysbiosis resulting from chronic HIV-1 viral protein exposure may afford insight into the mechanisms underlying HIV-1-associated neurocognitive and/or affective alterations; mechanisms which can be subsequently targeted via novel therapeutics.

Original language	English
Article number	173592
Journal	Pharmacology Biochemistry and Behavior
Volume	229
DOIs	https://doi.org/10.1016/j.pbb.2023.173592
State	Published - Aug 2023

Bibliographical note

Publisher Copyright:
© 2023

Funding

This work was supported in part by grants from NIH ( National Institute on Drug Abuse , R01-DA013137 & R01-DA059310 to R.M.B. and C.F.M.; National Institute on Drug Abuse , K99-DA056288 to K.A.M.; National Institute on Drug Abuse , R01-DA054992 to M.S.; National Institute of Allergy and Infectious Diseases , R01-A155887 to J.L.K.; National Institute of Mental Health , R01-MH106392 to C.F.M. and R.M.B.; National Institute of Neurological Disorders and Stroke , R01-NS100624 to C.F.M. and R.M.B.) and the interdisciplinary research training program supported by the University of South Carolina Behavioral-Biomedical Interface Program ( T32-GM081740 ).

Funders	Funder number
University of South Carolina Behavioral-Biomedical Interface Program	T32-GM081740
National Institutes of Health (NIH)
National Institute of Mental Health	R01-MH106392
National Institute on Drug Abuse	R01-DA059310, R01-DA054992, K99-DA056288, R01-DA013137
National Institute of Allergy and Infectious Diseases	R01-A155887
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council	R01-NS100624

Keywords

Apathy
Brain-gut-microbiota Axis
Depression
HIV-1-associated neurocognitive disorders
Neurotransmission
Synaptic dysfunction

ASJC Scopus subject areas

Biochemistry
Toxicology
Pharmacology
Clinical Biochemistry
Biological Psychiatry
Behavioral Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.pbb.2023.173592

Cite this

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title = "Therapeutically targeting the consequences of HIV-1-associated gastrointestinal dysbiosis: Implications for neurocognitive and affective alterations",

abstract = "Approximately 50 % of the individuals living with human immunodeficiency virus type 1 (HIV-1) are plagued by debilitating neurocognitive impairments (NCI) and/or affective alterations. Sizeable alterations in the composition of the gut microbiome, or gastrointestinal dysbiosis, may underlie, at least in part, the NCI, apathy, and/or depression observed in this population. Herein, two interrelated aims will be critically addressed, including: 1) the evidence for, and functional implications of, gastrointestinal microbiome dysbiosis in HIV-1 seropositive individuals; and 2) the potential for therapeutically targeting the consequences of this dysbiosis for the treatment of HIV-1-associated NCI and affective alterations. First, gastrointestinal microbiome dysbiosis in HIV-1 seropositive individuals is characterized by decreased alpha (α) diversity, a decreased relative abundance of bacterial species belonging to the Bacteroidetes phylum, and geographic-specific alterations in Bacillota (formerly Firmicutes) spp. Fundamentally, changes in the relative abundance of Bacteroidetes and Bacillota spp. may underlie, at least in part, the deficits in γ-aminobutyric acid and serotonin neurotransmission, as well as prominent synaptodendritic dysfunction, observed in this population. Second, there is compelling evidence for the therapeutic utility of targeting synaptodendritic dysfunction as a method to enhance neurocognitive function and improve motivational dysregulation in HIV-1. Further research is needed to determine whether the therapeutics enhancing synaptic efficacy exert their effects by altering the gut microbiome. Taken together, understanding gastrointestinal microbiome dysbiosis resulting from chronic HIV-1 viral protein exposure may afford insight into the mechanisms underlying HIV-1-associated neurocognitive and/or affective alterations; mechanisms which can be subsequently targeted via novel therapeutics.",

keywords = "Apathy, Brain-gut-microbiota Axis, Depression, HIV-1-associated neurocognitive disorders, Neurotransmission, Synaptic dysfunction",

author = "Rodriguez, {Mason T.} and McLaurin, {Kristen A.} and Michael Shtutman and Kubinak, {Jason L.} and Mactutus, {Charles F.} and Booze, {Rosemarie M.}",

note = "Publisher Copyright: {\textcopyright} 2023",

year = "2023",

month = aug,

doi = "10.1016/j.pbb.2023.173592",

language = "English",

volume = "229",

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T1 - Therapeutically targeting the consequences of HIV-1-associated gastrointestinal dysbiosis

T2 - Implications for neurocognitive and affective alterations

AU - Rodriguez, Mason T.

AU - McLaurin, Kristen A.

AU - Shtutman, Michael

AU - Kubinak, Jason L.

AU - Mactutus, Charles F.

AU - Booze, Rosemarie M.

PY - 2023/8

Y1 - 2023/8

N2 - Approximately 50 % of the individuals living with human immunodeficiency virus type 1 (HIV-1) are plagued by debilitating neurocognitive impairments (NCI) and/or affective alterations. Sizeable alterations in the composition of the gut microbiome, or gastrointestinal dysbiosis, may underlie, at least in part, the NCI, apathy, and/or depression observed in this population. Herein, two interrelated aims will be critically addressed, including: 1) the evidence for, and functional implications of, gastrointestinal microbiome dysbiosis in HIV-1 seropositive individuals; and 2) the potential for therapeutically targeting the consequences of this dysbiosis for the treatment of HIV-1-associated NCI and affective alterations. First, gastrointestinal microbiome dysbiosis in HIV-1 seropositive individuals is characterized by decreased alpha (α) diversity, a decreased relative abundance of bacterial species belonging to the Bacteroidetes phylum, and geographic-specific alterations in Bacillota (formerly Firmicutes) spp. Fundamentally, changes in the relative abundance of Bacteroidetes and Bacillota spp. may underlie, at least in part, the deficits in γ-aminobutyric acid and serotonin neurotransmission, as well as prominent synaptodendritic dysfunction, observed in this population. Second, there is compelling evidence for the therapeutic utility of targeting synaptodendritic dysfunction as a method to enhance neurocognitive function and improve motivational dysregulation in HIV-1. Further research is needed to determine whether the therapeutics enhancing synaptic efficacy exert their effects by altering the gut microbiome. Taken together, understanding gastrointestinal microbiome dysbiosis resulting from chronic HIV-1 viral protein exposure may afford insight into the mechanisms underlying HIV-1-associated neurocognitive and/or affective alterations; mechanisms which can be subsequently targeted via novel therapeutics.

AB - Approximately 50 % of the individuals living with human immunodeficiency virus type 1 (HIV-1) are plagued by debilitating neurocognitive impairments (NCI) and/or affective alterations. Sizeable alterations in the composition of the gut microbiome, or gastrointestinal dysbiosis, may underlie, at least in part, the NCI, apathy, and/or depression observed in this population. Herein, two interrelated aims will be critically addressed, including: 1) the evidence for, and functional implications of, gastrointestinal microbiome dysbiosis in HIV-1 seropositive individuals; and 2) the potential for therapeutically targeting the consequences of this dysbiosis for the treatment of HIV-1-associated NCI and affective alterations. First, gastrointestinal microbiome dysbiosis in HIV-1 seropositive individuals is characterized by decreased alpha (α) diversity, a decreased relative abundance of bacterial species belonging to the Bacteroidetes phylum, and geographic-specific alterations in Bacillota (formerly Firmicutes) spp. Fundamentally, changes in the relative abundance of Bacteroidetes and Bacillota spp. may underlie, at least in part, the deficits in γ-aminobutyric acid and serotonin neurotransmission, as well as prominent synaptodendritic dysfunction, observed in this population. Second, there is compelling evidence for the therapeutic utility of targeting synaptodendritic dysfunction as a method to enhance neurocognitive function and improve motivational dysregulation in HIV-1. Further research is needed to determine whether the therapeutics enhancing synaptic efficacy exert their effects by altering the gut microbiome. Taken together, understanding gastrointestinal microbiome dysbiosis resulting from chronic HIV-1 viral protein exposure may afford insight into the mechanisms underlying HIV-1-associated neurocognitive and/or affective alterations; mechanisms which can be subsequently targeted via novel therapeutics.

KW - Apathy

KW - Brain-gut-microbiota Axis

KW - Depression

KW - HIV-1-associated neurocognitive disorders

KW - Neurotransmission

KW - Synaptic dysfunction

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DO - 10.1016/j.pbb.2023.173592

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C2 - 37390973

AN - SCOPUS:85164369795

SN - 0091-3057

VL - 229

JO - Pharmacology Biochemistry and Behavior

JF - Pharmacology Biochemistry and Behavior

M1 - 173592

ER -

Therapeutically targeting the consequences of HIV-1-associated gastrointestinal dysbiosis: Implications for neurocognitive and affective alterations

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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