Gut Microbiome Profiles and Associated Metabolic Pathways in HIV-Infected Treatment-Naïve Patients

Abstract

The normal composition of the intestinal microbiota is a key factor for maintaining healthy homeostasis, and accordingly, dysbiosis is well known to be present in HIV-1 patients. This article investigates the gut microbiota profile of antiretroviral therapy-naive HIV-1 patients and healthy donors living in Latin America in a cohort of 13 HIV positive patients (six elite controllers, EC, and seven non-controllers, NC) and nine healthy donors (HD). Microbiota compositions in stool samples were determined by sequencing the V3-V4 region of the bacterial 16S rRNA, and functional prediction was inferred using PICRUSt. Several taxa were enriched in EC compared to NC or HD groups, including Acidaminococcus, Clostridium methylpentosum, Barnesiella, Eubacterium coprostanoligenes, and Lachnospiraceae UCG-004. In addition, our data indicate that the route of infection is an important factor associated with changes in gut microbiome composition, and we extend these results by identifying several metabolic pathways associated with each route of infection. Importantly, we observed several bacterial taxa that might be associated with different viral subtypes, such as Succinivibrio, which were more abundant in patients infected by HIV subtype B, and Streptococcus enrichment in patients infected by subtype C. In conclusion, our data brings a significant contribution to the understanding of dysbiosis-associated changes in HIV infection and describes, for the first time, differences in microbiota composition according to HIV subtypes. These results warrant further confirmation in a larger cohort of patients.

Keywords: human immunodeficiency virus; metabolism; microbiome; sexual orientation; virus subtypes.

Figure 1

Taxonomic differences in fecal microbiota between HIV-1 positive patients and healthy donors. Relative abundance at phylum level (A); Cladogram of LefSe linear discriminant analysis (LDA) scores showing differentially abundant taxonomic clades with an LDA score >2.0 in the gut microbiota of HIV-1 patients and healthy donors (B); LDA scores of differentially abundant taxa in the gut microbiota of HIV-1 patients and healthy donors (C). The relative abundance of genera identified by LefSe as being differentially abundant in HIV-1 patients and healthy donors were compared using a Mann–Whitney test (D). * p < 0.05.

Figure 2

Taxonomic differences and inferred functional content of gut microbiota of healthy donors (HD), elite controllers (EC), and non-controllers (NC). LefSe results for the bacterial taxa that were significantly different between HD, EC, and NC groups. The cladogram showing differentially abundant taxonomic clades (A) and LDA scores showing significant differences between groups (B). Comparison of PICRUSt predicted KEGG function. The heatmap shows the relative abundance of pathways that were significantly different between HD and NC groups (C). Significant differences between groups were tested with Mann–Whitney test (FDR-adjusted p-value < 0.05).

Figure 3

Effects of HIV transmission route on the gut microbiota of HIV-1 positive patients. Principal Coordinate Analysis (PCoA) of Bray Curtis distances among HET, MSM, and IDU groups (A). LEfSe results for the bacterial taxa that were significantly different between HET, MSM, and IDU groups. The cladogram shows differentially abundant taxonomic clades (B), and LDA scores showing significant differences between groups (C). Heatmap of relative abundance pathways that were significantly different between HET and MSM groups (D). Significant differences between the two groups were tested with Mann–Whitney test (FDR-adjusted p-value < 0.05).

Figure 4

Effects on the gut microbiota according to HIV subtype B and C. LEfSe results for the bacterial taxa that were significantly different between HIV-B and HIV-C infected patients. The cladogram shows differentially abundant taxonomic clades (A) and LDA scores showing significant differences between groups (B). The relative abundance of genus identified by LEfSe as being differentially more abundant in HIV positive patients infected by HIV subtype B (C) and subtype C (D) were compared using a Mann–Whitney test. * p values <0.05.