Low Tryptophan in Breast Milk May Help Explain Health Gaps in Children Born to Women With HIV

Between 2001 and 2008, in a clinical trial in Zambia, women gave breast milk samples at intervals from one week after delivery to eighteen months. Those samples, 1,426 in all, from 326 women, have now yielded a finding that researchers at UCLA say may help explain a long-standing puzzle in maternal and child health. The study appears in Nature Communications.

The puzzle is this: about 1.3 million children are born each year to women living with HIV. Even when antiretroviral therapy prevents the virus from passing to them, these HIV-exposed but uninfected children fare worse. In low-income settings they face a 50% increase in mortality, along with more infections, growth problems, and cognitive challenges. Before antiretroviral therapy was available, their mortality was two to three times that of infants not exposed to HIV. Why they stay vulnerable has been a critical gap in the research.

Of the Zambian women, 288 were living with HIV and 38 were not. Using metabolomics, the team measured more than 800 metabolites in the milk. They then checked their results against a second group of 47 women in Haiti who were receiving antiretroviral therapy.

The central result concerned tryptophan, an essential amino acid thought to matter for infant immune function, growth, and brain development. Milk from women with HIV had roughly 50% less of it than milk from women without HIV, and the gap held across the entire 18-month period. The kynurenine-to-tryptophan ratio, a marker of immune activation, was significantly elevated at every visit.

To learn whether the shortfall was confined to the milk, the researchers also measured tryptophan and kynurenine in mothers' blood plasma. Plasma tryptophan was lower in women with HIV too. The team concludes that the milk deficit reflects depletion throughout the mothers' bodies, likely from reduced intestinal absorption, rather than a problem moving tryptophan into milk.

The milk of women with HIV also carried more of a newly discovered antiviral compound called ddhC, plus higher cytosine and dimethylarginine. All of these are consistent with chronic viral inflammation and interferon activation. The altered pattern persisted in the Haitian cohort, whose members were on antiretroviral therapy and had higher immune function, suggesting it still matters under modern treatment.

"We've known for years that children born to mothers living with HIV face greater health challenges, but we didn't fully understand why," said Dr. Grace Aldrovandi, the corresponding author, a professor of pediatrics and chief of infectious diseases at UCLA's David Geffen School of Medicine. She said tryptophan deficiency and altered metabolism may be a common denominator behind the immune, growth, and cognitive differences. Dr. Nicole Tobin, the lead author and also a professor of pediatrics there, called it particularly striking that the signature persists with effective therapy, which she said helps explain why these children still need extra support.

The authors are explicit that no one should act on this yet. Inflammation in HIV pushes tryptophan down pathways that can generate neurotoxic metabolites, so simply replacing tryptophan without modulating those pathways could cause harm. The team plans to test supplementation in animal models of chronic viral inflammation, looking for safe gains in immune function, growth, and cognition. Later studies will examine whether infants of mothers with HIV have lower systemic tryptophan and process it differently. If a safe intervention emerges, it could reach the 1.3 million children born each year to women with HIV.