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.

The aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repression

“…For example, during HIV-1 infection, CD4+ T cells are rapidly depleted, especially in gut associated lymphoid tissue (GALT). As a likely consequence, the gut microbiome of HIV-1 infected individuals are distinct in composition from healthy individuals (Bandera et al, 2018; Zilberman-Schapira et al, 2016). Furthermore, dysbiosis and T cell depletion in HIV-1 infected patients may lead to the breakdown of the intestinal barrier, leading to the systemic distribution of bacterial products, as evidenced by increased circulating lipopolysaccharide (LPS) levels (Brenchley et al, 2006).…”

The aryl hydrocarbon receptor and interferon gamma generate antiviral states via transcriptional repression

“…For example, during HIV-1 infection, CD4+ T cells are rapidly depleted, especially in gut associated lymphoid tissue (GALT). As a likely consequence, the gut microbiome of HIV-1 infected individuals are distinct in composition from healthy individuals 50,51 . Furthermore, dysbiosis and T cell depletion in HIV-1 infected patients may lead to the breakdown of the intestinal barrier, leading to the systemic distribution of bacterial products, as evidenced by increased circulating lipopolysaccharide (LPS) levels 52 .…”

Oxidative Stress during HIV Infection: Mechanisms and Consequences

“…In HIV-1 infected individuals, these abnormalities correlate with the enhanced oxidative kynurenine pathway of tryptophan catabolism [182, 183]. This pathway generates quinolinic acid, 3-hydroxykynurenine, and 3-hydroxyanthranilic acid, all of which are known to have the ability to generate free radicals [184].…”