HIV positive patients on antiretroviral therapy have an altered mucosal intestinal but not oral microbiome

Abstract

This study characterized compositional and functional shifts in the intestinal and oral microbiome in HIV-positive patients compared to uninfected individuals. 79 specimens were collected from 5 HIV-positive and 12 control subjects from five locations (colon brush, colon wash, TI brush, TI wash and saliva) during colonoscopy and at patient visits. Microbiome composition was characterized using 16S rRNA sequencing and microbiome function was predicted using bioinformatics tools (PICRUSt and Bugbase). Our analysis indicated that the {beta} diversity of all intestinal samples (colon brush, colon wash, TI brush, TI wash) from patients with HIV was significantly different from patients without HIV, as measured by weighted UniFrac distances. Specifically, bacteria from genera Prevotella, Fusobacterium, Eubacterium, Megasphaera, Mogibacterium and Mitsuokella were more abundant in samples from HIV-positive patients. On the other hand, bacteria from genera Ruminococus, Blautia, and Clostridium were more abundant in samples from HIV-negative patients. Additionally, HIV-positive patients had higher abundances of biofilm-forming and pathogenic bacteria. Furthermore, pathways related to translation and nucleotide metabolism were elevated in HIV-positive patients whereas pathways related to lipid and carbohydrates metabolism and membrane transport were positively correlated with samples from HIV-negative patients. Our analyses further showed variations in microbiome composition in HIV-positive and negative patients by sampling site, with samples from colon wash, colon brush and TI wash significant between groups while samples from TI brush and saliva were not significant. Taken together, here we report altered intestinal microbiome composition and function in patients with HIV compared to uninfected patients, though we found no changes in the oral microbiome. Author summaryOver 37 million people worldwide are living with HIV. Although the availability of antiretroviral therapy has significantly reduced the number of AIDS-related deaths, individuals living with HIV are at increased risk for opportunistic infections. We now know that HIV interacts with the trillions of bacteria, fungus, and viruses in the human body termed the microbiome. The advent of next generation sequencing has allowed us to characterize the composition of the microbiome and how HIV changes the microbiome composition to influence disease severity and progression. Previous studies have examined changes in the microbiome in HIV-positive and negative individuals. However, only a limited number of studies have compared variations in the oral and gastrointestinal microbiome with HIV infection. Furthermore, very few studies have looked at how the microbiome in HIV infection may vary by sampling site. Here, we detail how the oral and gastrointestinal microbiome changes with HIV infection and use 5 different sampling sites to gain a more comprehensive view of these changes by location. Our results show site-specific changes in the intestinal microbiome associated with HIV infection. Additionally, we show that while there are significant changes in the intestinal microbiome, there are no significant changes in the oral microbiome.