Micrograph from a transmission electron microscope of HIV. Credit: PhD Dre at English Wikipedia, CC BY-SA 3.0

Despite effective antiretroviral therapy, pregnant women living with HIV remain at elevated risk of preterm birth, low birth weight and infant illness. A new longitudinal study suggests that disruption of the maternal gut microbiome — and its metabolic outputs — may be a key mediator of these outcomes1.

Researchers in Pune followed 244 pregnant women, including 91 living with HIV, from mid-pregnancy to one year postpartum. In a sub-study, they collected stool samples every two weeks across the second and third trimesters and carried out 16S rRNA sequencing, and profiled 100 participants for circulating metabolites.

Women living with HIV showed persistently lower microbial alpha-diversity and a distinct gut community structure throughout pregnancy. Pro-inflammatory and outcome-linked genera — including Fusobacterium, Megamonas and Lachnoclostridium — were enriched in women living with HIV, whereas beneficial short-chain fatty acid producers such as Lachnospiraceae_NK4A136_group were depleted.

Metabolomic analysis identified 87 differentially abundant metabolites. Notably, N2,N2-dimethylguanosine — previously linked to preterm birth — was elevated. Multi-omics integration highlighted Fusobacterium as a central player: higher abundance correlated with reduced sphingomyelin, suggesting altered lipid metabolism, and increased 2-hydroxyglutarate, showing compounded disruption of glutamate pathways already affected by HIV.

Strikingly, dysbiosis persisted after delivery. At six months, 42 microbial taxa were absent in HIV-exposed but uninfected infants compared with unexposed peers, pointing to intergenerational consequences.

The results suggest that the maternal gut microbiome may be an intervention point to improve pregnancy outcomes and safeguard infant health in the context of HIV.