Tobin Nicole H, Li Fan, Zhu Wentao, Ferbas Kathie G, Sleasman John W, Raftery Daniel, Kuhn Louise, Aldrovandi Grace M
Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at the University of California, Los Angeles, CA, USA.
UW Northwest Metabolomics Center, Seattle, WA, USA.
Nat Commun. 2025 Oct 28;16(1):9437. doi: 10.1038/s41467-025-64566-w.
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.
感染艾滋病毒的女性（WLWH）所生子女的发病率增加，在低收入环境中，其死亡率是未感染艾滋病毒女性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，因为健康益处大于传播风险，特别是在提供孕产妇抗逆转录病毒治疗时。我们使用全局代谢组学对326名感染和未感染艾滋病毒的女性在产后18个月进行纵向采样，分析她们乳汁的代谢组。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，这些都与孕产妇艾滋病毒感染密切相关。乳汁和血浆中色氨酸和犬尿氨酸的定量水平表明，这些扰动反映了感染艾滋病毒的女性中色氨酸的全身消耗和色氨酸分解代谢的改变。最后，我们在一组更健康的感染艾滋病毒的女性独立队列中验证了这些孕产妇艾滋病毒感染的特征。综上所述，我们的研究结果表明，感染艾滋病毒的女性乳汁中色氨酸含量和可利用性降低，这可能表明乳汁中色氨酸分解代谢受到扰动。这种扰动与感染艾滋病毒的女性所生孩子发病率和死亡率增加之间的联系值得进一步研究。
