The gut microbiome and metabolome of people living with HIV altered during treatment.

Background: Despite effective viral suppression with antiretroviral therapy (ART), people living with HIV (PLWH) often experience persistent immune activation and incomplete immune reconstitution. Gut barrier disruption and gut microbial dysbiosis contribute to chronic inflammation in PLWH. Shen Ling Ai Cao pill (SLAC) may have immunomodulatory effects, however, changes in the gut microbiota and fecal metabolome during SLAC administration remain unclear. This study aimed to characterize changes in the gut microbiota and fecal metabolome during SLAC administration in PLWH. Methods: In this single-arm study, 46 PLWH on long-term ART received adjunctive SLAC for 6 months. Fecal samples were collected, and peripheral CD4+ and CD8+ T-cell counts and the CD4/CD8 ratio were measured at baseline and month 6. Gut microbiota were profiled by 16S rRNA gene sequencing, and untargeted metabolomics was performed to characterize fecal metabolic changes. Microbial diversity, differential taxa, functional pathways, differential metabolites, and KEGG enrichment were analyzed. Correlation analyses were conducted to explore associations among gut microbiota, metabolites, and T-cell subsets. Results: Among the 46 PLWH enrolled, 42 completed the 6-month follow-up and were included in the final analysis. From M0 to M6, median CD8+ T-cell counts increased from 448.5 to 565.0 cells/mm Conclusions: In this single-arm longitudinal study of ART-treated PLWH, 6 months of adjunctive SLAC administration was associated with changes in fecal microbial composition, fecal metabolomic profiles, and CD8+ T cell counts, whereas CD4+ T cell counts showed a nonsignificant increasing trend. Controlled studies are needed to determine whether these changes are attributable to SLAC.