Gut resistome linked to sexual preference and HIV infection

Abstract

Background: People living with HIV (PLWH) are at increased risk of acquisition of multidrug resistant organisms due to higher rates of predisposing factors. The gut microbiome is the main reservoir of the collection of antimicrobial resistance determinants known as the gut resistome. In PLWH, changes in gut microbiome have been linked to immune activation and HIV-1 associated complications. Specifically, gut dysbiosis defined by low microbial gene richness has been linked to low Nadir CD4 + T-cell counts. Additionally, sexual preference has been shown to strongly influence gut microbiome composition in PLWH resulting in different Prevotella or Bacteroides enriched enterotypes, in MSM (men-who-have-sex-with-men) or no-MSM, respectively. To date, little is known about gut resistome composition in PLWH due to the scarcity of studies using shotgun metagenomics. The present study aimed to detect associations between different microbiome features linked to HIV-1 infection and gut resistome composition.

Results: Using shotgun metagenomics we characterized the gut resistome composition of 129 HIV-1 infected subjects showing different HIV clinical profiles and 27 HIV-1 negative controls from a cross-sectional observational study conducted in Barcelona, Spain. Most no-MSM showed a Bacteroides-enriched enterotype and low microbial gene richness microbiomes. We did not identify differences in resistome diversity and composition according to HIV-1 infection or immune status. However, gut resistome was more diverse in MSM group, Prevotella-enriched enterotype and gut micorbiomes with high microbial gene richness compared to no-MSM group, Bacteroides-enriched enterotype and gut microbiomes with low microbial gene richness. Additionally, gut resistome beta-diversity was different according to the defined groups and we identified a set of differentially abundant antimicrobial resistance determinants based on the established categories.

Conclusions: Our findings reveal a significant correlation between gut resistome composition and various host variables commonly associated with gut microbiome, including microbiome enterotype, microbial gene richness, and sexual preference. These host variables have been previously linked to immune activation and lower Nadir CD4 + T-Cell counts, which are prognostic factors of HIV-related comorbidities. This study provides new insights into the relationship between antibiotic resistance and clinical characteristics of PLWH.

Keywords: Antimicrobial resistance; Gut microbiome; Gut resistome; HIV infection; Shotgun metagenomics.

Fig. 1

Differences in gut resistome alpha diversity measured by Shannon and Inverse Simpson diversity indexes according to sexual preference (A) and gene richness (B). Group differences were calculated using one-sided Wilcoxon tests

Fig. 2

Non-metric multidimensional scaling (NMDS) plot based on resistome Bray–Curtis (BC) dissimilarity between samples stratified per sexual preference (A) and gene richness (B). Ellipses represent 95% confidence intervals. The stress of the ordination effect sizes (r²) calculated by PERMANOVA tests and corresponding p-values are shown in the plots

Fig. 3

Non-metric multidimensional scaling (NMDS) plot based on resistome Bray–Curtis (BC) dissimilarity between samples. Dot colours represent sexual preference. Antimicrobial resistance gene families significantly (p < 0.05) associated to an environmental vector of more than 0.2 NMDS length are represented