HIV Infection is associated with compositional and functional shifts in the rectal mucosal microbiota

Abstract

BackgroundRegardless of infection route, the intestine is the primary site for HIV-1 infection establishment and results in significant mucosal CD4+ T lymphocyte depletion, induces an inflammatory state that propagates viral dissemination, facilitates microbial translocation, and fosters establishment of one of the largest HIV reservoirs. Here we test the prediction that HIV infection modifies the composition and function of the mucosal commensal microbiota.ResultsRectal mucosal microbiota were collected from human subjects using a sponge-based sampling methodology. Samples were collected from 20 HIV-positive men not receiving combination anti-retroviral therapy (cART), 20 HIV-positive men on cART and 20 healthy, HIV-negative men. Microbial composition of samples was analyzed using barcoded 16S Illumina deep sequencing (85,900 reads per sample after processing). Microbial metagenomic information for the samples was imputed using the bioinformatic tools PICRUST and HUMAnN. Microbial composition and imputed function in HIV-positive individuals not receiving cART was significantly different from HIV-negative individuals. Genera including Roseburia, Coprococcus, Ruminococcus, Eubacterium, Alistipes and Lachnospira were depleted in HIV-infected subjects not receiving cART, while Fusobacteria, Anaerococcus, Peptostreptococcus and Porphyromonas were significantly enriched. HIV-positive subjects receiving cART exhibited similar depletion and enrichment for these genera, but were of intermediate magnitude and did not achieve statistical significance. Imputed metagenomic functions, including amino acid metabolism, vitamin biosynthesis, and siderophore biosynthesis differed significantly between healthy controls and HIV-infected subjects not receiving cART.ConclusionsHIV infection was associated with rectal mucosal changes in microbiota composition and imputed function that cART failed to completely reverse. HIV infection was associated with depletion of some commensal species and enrichment of a few opportunistic pathogens. Many imputed metagenomic functions differed between samples from HIV-negative and HIV-positive subjects not receiving cART, possibly reflecting mucosal metabolic changes associated with HIV infection. Such functional pathways may represent novel interventional targets for HIV therapy if normalizing the microbial composition or functional activity of the microbiota proves therapeutically useful.

Effects of Fecal Microbial Transplantation on Microbiome and Immunity in Simian Immunodeficiency Virus-Infected Macaques

“…In chronic HIV infection, an altered gut microbiome is associated with mucosal dysfunction, systemic inflammation, and disease progression (9,10,12,39). FMT is emerging as an effective treatment option for antibiotic-refractory intestinal infections, such as C. difficile infections, as well as for chronic inflammatory conditions of the gut that are known to be associated with dysbiosis (24,25,40).…”

Lack of Vitamin D Receptor Causes Dysbiosis and Changes the Functions of the Murine Intestinal Microbiome

“…Bacterial genomes were imputed according to the similarity of sequenced genomes to reference GreenGenes sequences. 25 …”

“…12 VDR regulates the expression of cathelicidin antimicrobial peptides (CAMPs), β-defensins, and autophagy regulator ATG16L1 [13][14][15] and therefore possesses some antibiotic properties. For example, [1,25(OH) 2 D 3 ] leads to up-regulation of CAMPs and the killing of intracellular Mycobacterium tuberculosis in human monocytes. 16 These findings give rise to the inference that vitamin D/VDR signaling may dramatically change the bacterial landscape in the gut.…”

Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals

“…Mounting evidence suggests that disruption of gut immunity in HIV infection also precipitates dysbiosis of the gut microbial community, which negatively affects critical pathways for healthy immune homeostasis. [11][12][13][14][15][16][17] In particular, the extent of dysbiosis correlates with the activity of the kynurenine pathway of tryptophan catabolism and with plasma concentrations of the inflammatory cytokine interleukin-6 (IL-6), both of which are established markers of disease progression. 11 Simultaneously, compositional and functional shifts in the gut microbiota have been described in most of the illnesses that drive excess of mortality during treated HIV infection.…”