Dataset Information

Alcohol Use Is Associated With Intestinal Dysbiosis and Dysfunctional CD8+ T-Cell Phenotypes in Persons With Human Immunodeficiency Virus.

ABSTRACT:

Background

Inflammation persists among persons with human immunodeficiency virus (PWH) despite effective antiretroviral therapy and may contribute to T-cell dysfunction. Alcohol use is prevalent among PWH and promotes intestinal leak, dysbiosis, and a proinflammatory milieu. Whether alcohol use is associated with T-cell late differentiation remains to be investigated.

Methods

Data and samples from PWH (N = 359 of 365) enrolled in the New Orleans Alcohol Use in HIV Study were used. Alcohol use was assessed by self-report (Alcohol Use Disorders Identification Test; lifetime alcohol exposure; 30-day Alcohol Timeline Followback) and phosphatidylethanol (PEth) quantitation. In a subset of participants, fecal bacterial content was assessed by ribosomal 16S marker gene deep sequencing and quantitative polymerase chain reaction. Intestinal leak was assessed by fecal-to-plasma α-1-antitrypsin (A1AT) enzyme-linked immunosorbent assay ratio. Peripheral T-cell populations were quantified by flow cytometry.

Results

Alcohol Use Disorder Identification Test scores were positively associated with activated-senescent, exhausted, and terminal effector memory CD45RA+CD8+ but not CD4+ T cells (cells/μL) after confounder adjustment (P < .050). Phosphatidylethanol was positively associated with A1AT (P < .050). The PEth and activated-senescent CD8+ were associated with bacterial β-diversity (P < .050) and positively associated with the relative abundance of coabundant Prevotellaceae members (q < .100).

Conclusions

Alcohol use among PWH is associated with CD8+ T-cell late differentiation, intestinal leak, and dysbiosis. Alcohol-associated dysbiosis is implicated in CD8+ T-cell senescence.

SUBMITTER: Maffei VJ

PROVIDER: S-EPMC8006423 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Alcohol Use Is Associated With Intestinal Dysbiosis and Dysfunctional CD8+ T-Cell Phenotypes in Persons With Human Immunodeficiency Virus.

Maffei Vincent J VJ Siggins Robert W RW Luo Meng M Brashear Meghan M MM Mercante Donald E DE Taylor Christopher M CM Molina Patricia P Welsh David A DA

The Journal of infectious diseases 20210301 6

<h4>Background</h4>Inflammation persists among persons with human immunodeficiency virus (PWH) despite effective antiretroviral therapy and may contribute to T-cell dysfunction. Alcohol use is prevalent among PWH and promotes intestinal leak, dysbiosis, and a proinflammatory milieu. Whether alcohol use is associated with T-cell late differentiation remains to be investigated.<h4>Methods</h4>Data and samples from PWH (N = 359 of 365) enrolled in the New Orleans Alcohol Use in HIV Study were used. ...[more]

PMID: 32725203

Similar Datasets

Project description:Chronic alcohol consumption perturbs the normal intestinal microbial communities (dysbiosis). To investigate the relationship between alcohol-mediated dysbiosis and pulmonary host defense we developed a fecal adoptive transfer model, which allows us to investigate the impact of alcohol-induced gut dysbiosis on host immune response to an infectious challenge at a distal organ, independent of prevailing alcohol use. Male C57BL/6 mice were treated with a cocktail of antibiotics (ampicillin, gentamicin, neomycin, vancomycin, and metronidazole) via daily gavage for two weeks. A separate group of animals was fed a chronic alcohol (or isocaloric dextrose pair-fed controls) liquid diet for 10 days. Microbiota-depleted mice were recolonized with intestinal microbiota from alcohol-fed or pair-fed (control) animals. Following recolonization groups of mice were sacrificed prior to and 48 hrs. post respiratory infection with Klebsiella pneumoniae. Klebsiella lung burden, lung immunology and inflammation, as well as intestinal immunology, inflammation, and barrier damage were examined. Results showed that alcohol-associated susceptibility to K. pneumoniae is, in part, mediated by gut dysbiosis, as alcohol-naïve animals recolonized with a microbiota isolated from alcohol-fed mice had an increased respiratory burden of K. pneumoniae compared to mice recolonized with a control microbiota. The increased susceptibility in alcohol-dysbiosis recolonized animals was associated with an increase in pulmonary inflammatory cytokines, and a decrease in the number of CD4+ and CD8+ T-cells in the lung following Klebsiella infection but an increase in T-cell counts in the intestinal tract following Klebsiella infection, suggesting intestinal T-cell sequestration as a factor in impaired lung host defense. Mice recolonized with an alcohol-dysbiotic microbiota also had increased intestinal damage as measured by increased levels of serum intestinal fatty acid binding protein. Collectively, these results suggest that alterations in the intestinal immune response as a consequence of alcohol-induced dysbiosis contribute to increased host susceptibility to Klebsiella pneumonia.

Project description:BACKGROUND:Substance use is common among people with human immunodeficiency virus (HIV) infection. Alcohol, marijuana, and HIV can have negative effects on cognition. Associations between current and lifetime marijuana and alcohol use and cognitive dysfunction in people with HIV infection were examined. METHODS:Some 215 HIV-infected adults with Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) substance dependence or ever injection drug use were studied. In adjusted cross-sectional regression analyses associations were assessed between current marijuana use, current heavy alcohol use, lifetime marijuana use, lifetime alcohol use, duration of heavy alcohol use (the independent variables), and 3 measures of cognitive dysfunction (dependent variables): both the (i) memory and (ii) attention domains from the Montreal Cognitive Assessment (MoCA) and the (iii) 4-item cognitive function scale (CF4) from the Medical Outcomes Study HIV Health Survey (MOS-HIV). Analyses were adjusted for demographics, primary language, depressive symptoms, anxiety, comorbidities, antiretroviral therapy, hepatitis C virus (ever), duration of HIV infection (years), HIV-viral load (log copies/mL), CD4 cell count, lifetime and recent cocaine use, and recent illicit and prescribed opioid use. RESULTS:Current marijuana use was significantly and negatively associated with the MOS-HIV CF4 score (adjusted mean difference = -0.40, P = .01). Current marijuana use was not significantly associated with either MoCA score. Lifetime marijuana use and current heavy and lifetime alcohol use and duration of heavy alcohol use were not associated with any measure of cognitive dysfunction. CONCLUSION:Current marijuana use was associated with one measure of cognitive dysfunction, but there was not a consistent pattern of association with lifetime marijuana use or alcohol use and measures of cognitive dysfunction. Understanding the mechanism by which marijuana, with and without alcohol, are associated with worse cognition warrants larger, longer studies with more precise and diverse measurements of cognitive function.

Dataset Information

Alcohol Use Is Associated With Intestinal Dysbiosis and Dysfunctional CD8+ T-Cell Phenotypes in Persons With Human Immunodeficiency Virus.

Background

Methods

Results

Conclusions

Publications

Alcohol Use Is Associated With Intestinal Dysbiosis and Dysfunctional CD8+ T-Cell Phenotypes in Persons With Human Immunodeficiency Virus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets