Multi-omic study of the HIV gut-associated microbiome

HIV infection causes a disruption of the gut associated lymphoid tissue that shifts the composition of the colonic bacterial community. Here, we present the results of a holistic multi-omic study, which implemented system biology analyses and probabilistic models in order to understand the effect of the gut dysbiosis over the host health in a cohort of HIV-infected subjects and controls. The microbiome was characterized by sequencing the metagenome and the metatranscriptome, which were correlated with immunological predictors of disease progression, including indirect markers of bacterial translocation. We observed that the dysbiotic community is enriched in Gram-negative species, which are adapted to the inflammatory environment of the gut produced by the HIV infection. The microbiota produced pro-inflammatory metabolites, which correlated with markers of systemic immune activation and inflammation. Moreover, the HIV-associated dysbiosis is depleted of short chain fatty acid (SCFA)-producer species and showed a low expression of genes related to anti-inflammatory SCFA metabolic pathways. Additionally, the ecological and metabolic network analysis showed that the dysbiotic community is able to achieve a stable configuration, which is associated with the immunological markers. Finally, we model a Bayesian network which included data from metagenomic, metatranscriptomic and metabolomic data. The network shows that the functional potential of the microbiome is the most determinant factor to maintain the microbiome network structure being the expression of the butanoate metabolism pathway the factor that most influences the immune system.