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. 2016 Oct 1;214 Suppl 2(Suppl 2):S58-66.
doi: 10.1093/infdis/jiw258.

Gut Mucosal Barrier Dysfunction, Microbial Dysbiosis, and Their Role in HIV-1 Disease Progression

Joseph C Mudd  1 , Jason M Brenchley  1
Affiliations

Gut Mucosal Barrier Dysfunction, Microbial Dysbiosis, and Their Role in HIV-1 Disease Progression

Joseph C Mudd et al. J Infect Dis. .

Abstract

Distinct pathological events occur within the gastrointestinal (GI) tract of Asian macaques with progressive simian immunodeficiency virus (SIV) infection and humans with human immunodeficiency virus type 1 (HIV-1) infection that are critical in shaping disease course. These events include depletion and functional alteration of GI-resident CD4(+) T cells, loss of antigen-presenting cells, loss of innate lymphocytes, and possible alterations to the composition of the gut microbiota. These contribute to structural damage to the GI tract and systemic translocation of GI tract microbial products. These translocated microbial products directly stimulate the immune system, and there is now overwhelming evidence that this drives chronic immune activation in HIV-1 and SIV infection. While combined antiretroviral therapy (cART) in HIV-1-infected subjects generally allows for immune reconstitution in peripheral blood, reconstitution of the GI tract occurs at a much slower pace, and both immunological and structural abnormalities persist in the GI tract. Importantly, studies of large cohorts of individuals have linked suboptimal GI reconstitution to residual inflammation and heightened morbidities in HIV-1-infected cART recipients. As a result, current era treatments aimed at augmenting restoration of the GI tract hold promise in returning cART recipients to full health.

Keywords: HIV-1 pathognesis; Th17; cART; gastrointestinal tract; microbiome; probiotics; residual inflammation.

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Figures

Figure 1.
Figure 1.
Gastrointestinal (GI) damage is not fully reversed during human immunodeficiency virus type 1 (HIV-1) infection, despite immune reconstitution in peripheral blood. Viral replication, chronic inflammation, and loss of interleukin 17 (IL-17)–producing cells (Th17/Tc17) cause irreparable damage to the GI tract, inducing the translocation of commensal microbes from the lumen into the systemic circulation. The GI microenvironment does not fully normalize with combined antiretroviral therapy (cART), despite apparent immune reconstitution in peripheral blood. Abbreviation: ILC, innate lymphoid cell.
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