The gut microbiome in human immunodeficiency virus infection

Abstract

HIV/AIDS causes severe dysfunction of the immune system through CD4+ T cell depletion, leading to dysregulation of both the adaptive and innate immune arms. A primary target for viral infection is the gastrointestinal tract, which is a reservoir of CD4+ T cells. In addition to being a major immune hub, the human gastrointestinal tract harbors trillions of commensal microorganisms, the microbiota, which have recently been shown to play critical roles in health. Alterations in the composition and function of microbiota have been implicated in a variety of 'multi-factorial' disorders, including infectious, autoimmune, metabolic, and neoplastic disorders. It is widely accepted that, in addition to its direct role in altering the gastrointestinal CD4+ T cell compartment, HIV infection is characterized by gut microbiota compositional and functional changes. Herein, we review such alterations and discuss their potential local and systemic effects on the HIV-positive host, as well as potential roles of novel microbiota-targeting treatments in modulating HIV progression and associated adverse systemic manifestations.

Keywords: AIDS; Anti-retroviral therapy; CD4+ T cells; Dysbiosis; Gastrointestinal tract; HIV; Microbiota.

Fig. 1

Gut microbiota alterations during HIV infection and their potential effects on the host. a. In different studies, distinct gut microbiome compositions have been identified in HIV infected individuals with or without ART, as compared to healthy controls. Importantly, HIV-associated microbiome configurations vary between these studies. While ART dramatically lowers the viral load in infected individuals, gut microbiome composition is not fully restored to a healthy composition. ‘Elite controllers’ differ in their microbial composition from HIV- infected individuals and are more similar to healthy individuals. b. The characteristic HIV microbiota possibly contributes to some of the common HIV manifestations, including modification of the level if infectivity, occurrence of opportunistic infections, increased gut permeability and resultant bacteria and bacterial product translocation, increased immune activation and T cell polarization, metabolic complications and variability in the response to HIV treatment