Gut microbiota diversity predicts immune status in HIV-1 infection

Nowak, Piotr; Trøseid, Marius; Avershina, Ekaterina; Barqasho, Babilonia; Neogi, Ujjwal; Holm, Kristian; Hov, Johannes R.; Noyan, Kajsa; Vesterbacka, Jan; Svärd, Jenny; Rudi, Knut; Sönnerborg, Anders

doi:10.1097/qad.0000000000000869

Cited by 247 publications

(326 citation statements)

References 41 publications

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“…Studies investigating the intestinal microbiome in the setting of HIV-1 infection have used a number of different sequence-based technologies to comprehensively identify and enumerate the constituents of complex, host-associated bacterial communities[37-53]. Although most recent studies used the highly conserved gene encoding the small-subunit ribosomal RNA gene (16S in bacteria/archaea or 18S rRNA in eucaryotes) to infer the types of microorganisms present in a community, the particular hypervariable (V) sub-regions of the 16S gene that were targeted (due to the fact that most next-generation sequencing platforms cannot generate full-length 16S sequences) differed; a number of studies amplified and sequenced the ~250 bp V4 region[37, 40, 42, 43, 53], whereas other studies amplified V1V3[49], V3V4[46, 48, 52], V3V5[39, 50] or V6[47] regions (~530 bp, ~460 bp, ~570 bp, and ~120 bp, respectively). The choice of hypervariable region and particular broad-range primers used for PCR amplification undoubtedly affect the resulting sequence dataset(s) since V regions differ intrinsically in their abilities to resolve phylogeny[24, 54, 55].…”

Section: Microbiome Analysismentioning

confidence: 99%

“…Indeed, reductions in diversity have been observed in both untreated and treated HIV-infected subjects compared to uninfected control subjects in mucosal[42, 44] and fecal samples[43, 44, 46, 48]. Surprisingly, bacterial diversity further decreased in stool samples of HIV-1 infected study participants who were followed after the introduction of ART[46] suggesting antiretroviral drugs themselves may impact the intestinal microbiota. Men who have sex with men (MSM) were found to have greater fecal microbial diversity than non-MSM, but HIV-associated reductions in diversity persisted even when HIV-1 infected subjects were stratified for MSM vs. non-MSM[45].…”

Section: Alterations In the Diversity Of Intestinal Bacterial Communimentioning

confidence: 99%

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The gut microbiome and HIV-1 pathogenesis

Dillon

Frank²,

Wilson³

2016

Aids

129

113

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HIV-1 infection is associated with substantial damage to the gastrointestinal (GI) tract resulting in structural impairment of the epithelial barrier and a disruption of intestinal homeostasis. The accompanying translocation of microbial products and potentially microbes themselves from the lumen into systemic circulation has been linked to immune activation, inflammation, and HIV-1 disease progression. The importance of microbial translocation in the setting of HIV-1 infection has led to a recent focus on understanding how the communities of microbes that make up the intestinal microbiome are altered during HIV-1 infection and how they interact with mucosal immune cells to contribute to inflammation. This review details the dysbiotic intestinal communities associated with HIV-1 infection and their potential link to HIV-1 pathogenesis. We detail studies that begin to address the mechanisms driving microbiota-associated immune activation and inflammation and the various treatment strategies aimed at correcting dysbiosis and improving the overall health of HIV-1 infected individuals. Finally, we discuss how this relatively new field of research can advance to provide a more comprehensive understanding of the contribution of the gut microbiome to HIV-1 pathogenesis.

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Section: Microbiome Analysismentioning

confidence: 99%

Section: Alterations In the Diversity Of Intestinal Bacterial Communimentioning

confidence: 99%

The gut microbiome and HIV-1 pathogenesis

Dillon

Frank²,

Wilson³

2016

Aids

129

113

View full text Add to dashboard Cite

show abstract

“…22 Of note, we and others have recently shown that HIV-associated changes in gut microbiota are not restored on suppressive ART, providing the rationale for targeting the gut microbiota in treated HIV infection. 18,20,23 Moreover, prebiotic supplementation seemed to increase the percentage of Bifidobacterium and to reduce soluble (s)CD14 levels in HIV-infected patients. 24 Serrano-Villar et al 25 recently reported partly reversed HIVassociated dysbiosis after intervention with prebiotics and glutamine.…”

Section: Introductionmentioning

confidence: 96%

Reduced Levels of D-dimer and Changes in Gut Microbiota Composition After Probiotic Intervention in HIV-Infected Individuals on Stable ART

Stiksrud

Nowak

Nwosu

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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“…Results from a study by Gaardbo et al showed that microberelated effects in the gut are associated with CD4 T-cell loss during HIV-1 infection (35). The dysbiosis that occurs in the gut of HIV-1-infected subjects persisting on ART describes the imbalance of bacterial diversity that is illustrated by increased proinflammatory pathogenic strains (63,64). Importantly, the enhanced tryptophan metabolism related to the composition of the gut microbiota has been linked to the disease progression contributed by enhanced Kyn production in the gut (65).…”

Section: Ccr7mentioning

confidence: 99%

Kynurenine Reduces Memory CD4 T-Cell Survival by Interfering with Interleukin-2 Signaling Early during HIV-1 Infection

Dagenais-Lussier

Aounallah

Mehraj

et al. 2016

J Virol

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Early HIV-1 infection is characterized by enhanced tryptophan catabolism, which contributes to immune suppression and disease progression. However, the mechanism by which kynurenine, a tryptophan-related metabolite, induces immune suppression remains poorly understood. Herein, we show that the increased production of kynurenine correlates with defective interleukin-2 (IL-2) signaling in memory CD4 T cells from HIV-infected subjects. Defective IL-2 signaling in these subjects, which drives reduced protection from Fas-mediated apoptosis, was also associated with memory CD4 T-cell loss. Treatment of memory CD4 T cells with the concentration of kynurenine found in plasma inhibited IL-2 signaling through the production of reactive oxygen species. We further show that IL-2 signaling in memory CD4 T cells is improved by the antioxidant N-acetylcysteine. Early initiation of antiretroviral therapy restored the IL-2 response in memory CD4 T cells by reducing reactive oxygen species and kynurenine production. The study findings provide a kynurenine-dependent mechanism through IL-2 signaling for reduced CD4 T-cell survival, which can be reversed by early treatment initiation in HIV-1 infection. IMPORTANCE The persistence of functional memory CD4 T cells represents the basis for long-lasting immune protection in individuals after exposure to HIV-1. Unfortunately, primary HIV-1 infection results in the massive loss of these cells within weeks of infection, which is mainly driven by inflammation and massive infection by the virus. These new findings show that the enhanced production of kynurenine, a metabolite related to tryptophan catabolism, also impairs memory CD4 T-cell survival and interferes with IL-2 signaling early during HIV-1 infection.P rogressive depletion of CD4 T cells by pyroptosis and activation-related apoptosis is the hallmark of HIV-1 infection (1-4). The loss of memory CD4 T cells and, in particular, central memory CD4 T cells (T CM cells), which are critical to ensure longlasting immune protection, occurs from the onset of infection and independently predicts disease progression (5-8). Memory T-cell survival depends on signals provided by the gamma-chain-receptor cytokines, such as interleukin-2 (IL-2) and IL-7 (9-12). Previous data showed an impaired response to these cytokines in T cells during HIV-1 infection (13-16). However, our knowledge of the molecular mechanisms responsible for these immune defects is still incomplete.CD4 T-cell depletion is also linked with persistent inflammation, which takes place in the gut and lymphoid tissues early after infection and in the bloodstream later after infection (17-19). This inflammation is clinically relevant, since it has not been fully abrogated by long-term antiretroviral therapy (ART) (20)(21)(22)(23). Persistent inflammation during HIV-1 infection is associated with enhanced metabolic activity, which drives a Warburg-like effect on lipid, glucose, and amino acid pathways (22,(24)(25)(26)(27). The catabolism of an essential amino acid like tryptoph...

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Gut microbiota diversity predicts immune status in HIV-1 infection

Abstract: Gut microbiota alterations are closely associated with immune dysfunction in HIV-1 patients, and these changes persist during short-term ART. Our data implicate that re-shaping the microbiota may be an adjuvant therapy in patients commencing successful ART.

Cited by 247 publications

References 41 publications

The gut microbiome and HIV-1 pathogenesis

The gut microbiome and HIV-1 pathogenesis

Reduced Levels of D-dimer and Changes in Gut Microbiota Composition After Probiotic Intervention in HIV-Infected Individuals on Stable ART

Kynurenine Reduces Memory CD4 T-Cell Survival by Interfering with Interleukin-2 Signaling Early during HIV-1 Infection

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