The Human Gut Microbiome and Its Metabolic Pathways Dynamics Before and During HIV Antiretroviral Therapy

The human gut microbiome consists of highly complex microbial populations that play important roles in disease pathogenesis. Changes in the gut microbiome are associated with HIV infection. However, it is unclear whether the gut microbiome dysbiosis is causally linked to disease or whether it simply reflects disease-induced changes in the host immune and metabolic systems. This study aims to describe and compare intestinal microbial compositions and derived metabolic pathways in people living with HIV (PL-HIV) from prior to antiretroviral therapy (ART) to six and twelve months after ART initiation, compared to HIV-negative individuals. Whole-genome microbiome sequencing coupled with bioinformatics analysis was used to characterize participants' intestinal microbial structures and derived metabolic pathways.Pre- and post-ART gut microbiota characterization of PL-HIV revealed substantial dysbiosis compared to HIV-negative people. An enrichment of pro-inflammatory microorganisms was the hallmark of dysbiosis in the PL-HIV pre-ART, with a decline in Proteobacteria at six months of ART, continuing until twelve months of ART. Lower proportions of Bacteroidetes were noted pre-ART, but they increased slightly at six months of ART before decreasing again at twelve months of ART. Additionally, we reported metabolic changes that are particularly important for health and are associated with dysbiosis both before and post-ART. Alteration of the pyruvate fermentation to the isobutanol metabolic pathway persisted in PL-HIV after twelve months of ART, and this mechanism was correlated with a decrease in Ruminococcus bromii species. ART initiation appears to lead to changes in several crucial metabolic pathways and may not entirely restore the dysbiosis of the gut microbiota caused by HIV.