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HIV-associated alteration in gut microbiota are associated
with increased inflammation and infection of enteric CD4+ T cells
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Reported by Jules Levin
Durban 2016 July 18-22
Brent Palmer
Authors
B. Palmer, C. Neff, S. Li, J. Schneider, T. Campbell, C. Lozupone
Institutions
University of Colorado, Denver, Medicine, Aurora, United States
Abstract
Background: HIV infection is associated with dramatic alterations of the enteric microbiome that often persist despite long-term otherwise successful Antiretroviral Therapy (ART). Alterations in gut microbiota have been correlated with HIV disease progression, inflammatory markers in the gut and with inflammatory and bacterial translocation markers in blood. A better understanding of the immune-modulatory properties in gut microbes that correlate with disease will allow for the exploration of microbial drivers of immune activation, HIV disease pathogenesis and co-morbidity.
Methods: We are collecting gut microbiome data from a large cohort of individuals living in Colorado and identifying bacteria whose prevalence correlates with disease status, ART, and with inflammatory and metabolic disease markers. To explore the immune-modulatory properties of these bacteria, we culture peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) isolated from resected gut tissue with bacteria isolated from patient stool and cultured bacteria that are increased or decreased with HIV infection. We then measure the impact of the stimulation on pro and anti-inflammatory cytokines, T cell activation, T regulatory cells, HIV co-receptors and levels of HIV infection.
Results:
Many bacterial species significantly change with HIV and correlate with inflammatory and translocation markers in blood in our study population.
Although stimulations of PBMC/LPMC with most bacteria induce both pro and anti-inflammatory cytokines, cultured bacteria that increase with HIV and fecal bacteria from HIV-infected individuals induce lower levels of T regulatory cells and anti-inflammatory IL-10. Furthermore, incubation of LPMCs with numerically dominant bacteria of the HIV-associated (Prevotella copri) but not health-associated (Bacteroides uniformis) gut microbiome resulted in increased infectivity of immune cells by HIV.
Conclusions:
These data suggest that a loss of anti-inflammatory (beneficial) bacteria with HIV infection has the potential to drive chronic inflammation observed in HIV-infected individuals. Furthermore, our infectivity assays indicate a potential role of the HIV-associated gut microbiome in disease transmission and progression. We are currently further exploring microbiome associations with HIV disease, inflammation and metabolic disease in populations in both the US and Zimbabwe.
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