Altered milk tryptophan and tryptophan metabolites in women living with HIV

Children born to women living with HIV (WLWH) suffer increased morbidity and, in low-income settings, have two to three times the mortality of infants born to women without HIV. The basis for this increase remains elusive. In low-income settings, breastfeeding is recommended because health benefits outweigh the risk of transmission, especially when maternal antiretroviral therapy is provided. We profile the milk metabolome of 326 women with and without HIV sampled longitudinally for 18 months postpartum using global metabolomics. We identify perturbations in several metabolites, including tryptophan, dimethylarginine, and a recently discovered antiviral ribonucleotide, that are robustly associated with maternal HIV infection. Quantitative tryptophan and kynurenine levels in both milk and plasma reveal that these perturbations reflect systemic depletion of tryptophan and alterations in tryptophan catabolism in WLWH. Finally, we validate these signatures of maternal HIV infection in an independent cohort of healthier WLWH. Taken together, our findings demonstrate that milk tryptophan content and availability decrease among WLWH, which may indicate perturbations in milk tryptophan catabolism. The link between this perturbation and the increased morbidity and mortality of children born to WLWH merits further investigation.