Tobin Nicole H, Li Fan, Zhu Wentao, Ferbas Kathie G, Sleasman John W, Raftery Daniel, Kuhn Louise, Aldrovandi Grace M
Division of InfecGous Diseases, Department of Pediatrics, David Geffen School of Medicine at the University of California, Los Angeles.
UW Northwest Metabolomics Center.
Res Sq. 2025 Mar 21:rs.3.rs-6229815. doi: 10.21203/rs.3.rs-6229815/v1.
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.
感染艾滋病毒的妇女（WWH）所生子女的发病率会增加，在低收入环境中，其死亡率是未感染艾滋病毒妇女所生婴儿的两到三倍。这种增加的原因仍然不明。在低收入环境中，建议进行母乳喂养，因为健康益处超过传播风险，尤其是在提供孕产妇抗逆转录病毒治疗的情况下。我们使用全球代谢组学方法，对326名产后18个月纵向采样的妇女的乳汁代谢组进行了分析。我们确定了几种代谢物的扰动，包括色氨酸、二甲基精氨酸和一种最近发现的抗病毒核糖核苷酸，这些扰动与孕产妇艾滋病毒感染密切相关。乳汁和血浆中的色氨酸和犬尿氨酸定量水平表明，这些扰动反映了WWH中色氨酸的全身消耗和色氨酸分解代谢的改变。我们的研究结果提供了有趣的证据，表明WWH所生儿童色氨酸可用性的降低和色氨酸分解代谢的扰动可能导致其发病率和死亡率增加。
