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Dysbiosis of the Gut Microbiota Is Associated with HIV Disease Progression and Tryptophan Catabolism
14 auth. Ivan Vujkovic-Cvijin, R. Dunham, S. Iwai, M. C. Maher, Rebecca G. Albright, M. J. Broadhurst, Ryan D. Hernandez, M. Lederman, Yong Huang, M. Somsouk, ...
Gut-resident microbial populations may influence intestinal homeostasis during HIV disease. Gut Reaction to HIV Despite the value placed on individuality in the western world, no human is an island. Indeed, every person carries trillions of microorg…
Gut-resident microbial populations may influence intestinal homeostasis during HIV disease. Gut Reaction to HIV Despite the value placed on individuality in the western world, no human is an island. Indeed, every person carries trillions of microorganisms in their intestine, and it’s becoming increasingly clear that the composition and interaction of these microorganisms can directly affect human health. Vujkovic-Cvijin et al. now demonstrate that this is the case for individuals infected with HIV, even those where viral load is controlled by therapy. The authors screened the intestinal microbiome for microbial drivers of HIV-associated immunopathology. They found that a dysbiotic mucosal microbial community associated with mucosal immune disruption, T cell activation, and chronic inflammation in HIV-infected subjects, even in patients controlled with antiviral therapy. They then looked further into the mechanism of this association and found that the extent of dysbiosis correlated with tryptophan catabolism and plasma concentrations of the inflammatory cytokine interleukin-6 (IL-6), two established markers of disease progression. Indeed, gut-resident bacteria with the capacity to metabolize tryptophan were found to be enriched in HIV-infected subjects. These data link gut-resident microbial populations with the immunopathogenesis of HIV and suggest that modulating this community could provide a new therapeutic strategy for managing HIV disease progression. Progressive HIV infection is characterized by dysregulation of the intestinal immune barrier, translocation of immunostimulatory microbial products, and chronic systemic inflammation that is thought to drive progression of disease to AIDS. Elements of this pathologic process persist despite viral suppression during highly active antiretroviral therapy (HAART), and drivers of these phenomena remain poorly understood. Disrupted intestinal immunity can precipitate dysbiosis that induces chronic inflammation in the mucosa and periphery of mice. However, putative microbial drivers of HIV-associated immunopathology versus recovery have not been identified in humans. Using high-resolution bacterial community profiling, we identified a dysbiotic mucosal-adherent community enriched in Proteobacteria and depleted of Bacteroidia members that was associated with markers of mucosal immune disruption, T cell activation, and chronic inflammation in HIV-infected subjects. Furthermore, this dysbiosis was evident among HIV-infected subjects undergoing HAART, and the extent of dysbiosis correlated with activity of the kynurenine pathway of tryptophan catabolism and plasma concentrations of the inflammatory cytokine interleukin-6 (IL-6), two established markers of disease progression. Gut-resident bacteria with capacity to catabolize tryptophan through the kynurenine pathway were found to be enriched in HIV-infected subjects, strongly correlated with kynurenine levels in HIV-infected subjects, and capable of kynurenine production in vitro. These observations demonstrate a link between mucosal-adherent colonic bacteria and immunopathogenesis during progressive HIV infection that is apparent even in the setting of viral suppression during HAART. This link suggests that gut-resident microbial populations may influence intestinal homeostasis during HIV disease.
Published in
Science Translational Medicine
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60
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9 | 2013 |
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