Work

Changes in the Gut Microbiota Composition and Metabolic Pathways in Six-Week-Old HIV Exposed Breastfed Infants Receiving Antiretroviral Prophylaxis

Year: 2026

Type: article

Abstract: Introduction: Understanding the association of HIV exposure, antiretroviral therapy (ART) prophylaxis and human milk oligosaccharides (HMOs) on the gut microbiota of breastfed infants is crucial for developing strategies to promote infant health. Our study explored gut microbiota diversity and development in breastfed infants, analysing the influence of nevirapine (NVP) in HIV Exposed infants and HMOs in HIV Unexposed infants. Methods: Infants delivered vaginally and exclusively breastfed were recruited from City Council Clinics in Harare, Zimbabwe, at six weeks postpartum. A total of 110 infants were enrolled, and stool samples were collected for shotgun metagenomic sequencing. Dried blood spots from HIV-exposed infants were analyzed for nevirapine using HPLC–MS/MS, and breast milk from HIV-uninfected mothers was analyzed for human milk oligosaccharides using UPLC–MS. Of the collected samples, 93 stool specimens passed all bioinformatics quality filters. Alpha diversity and beta diversity were assessed, and associations between microbial diversity and HIV exposure, nevirapine levels, and HMO concentrations were evaluated using MaAsLin2. Results: Our analysis showed no significant differences in microbial diversity across various NVP concentrations in HE infants or in 3’SL and 6’SL in the HU infants group ( p ≥ 0.05). HIV exposure was associated with higher levels of Stenotrophomonas maltophilia and Mediterraneibacter faecis (corrected p- values 2.08× 10 − 5 and 0.00246), respectively. Moreover, HIV exposure was linked to changes in specific metabolic pathways. Conclusion: Although overall diversity remained stable across NVP concentrations in HE infants and HMO levels in HU infants, specific taxa and functional pathways differed by HIV exposure, highlighting that compositional and functional changes can occur independently of global diversity metrics. Therefore, HIV exposure itself may influence gut microbiota composition and metabolic functions at species level, particularly with an increased abundance of specific bacteria and altered metabolic pathways leading to disturbances in vitamin metabolism. Keywords: HIV-exposed infants, gut microbiota, human milk oligosaccharides, antiretroviral prophylaxis

Source: Pediatric Health Medicine and Therapeutics

DOI: 10.2147/phmt.s596049