Altered milk tryptophan and tryptophan metabolites and health of children born to women with HIV

Children born to women with HIV (WWH) 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 profiled the milk metabolome of 326 women 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 WWH. Our findings provide intriguing evidence that decreases in tryptophan availability and perturbations in tryptophan catabolism in children born to WWH may contribute to their increased morbidity and mortality.