Breastmilk from mothers with HIV contains less tryptophan for immunity, researchers discover

Breast milk from women living with HIV contains significantly lower levels of tryptophan, an essential amino acid likely important for infant immune function, growth, and brain development.

This discovery from a recent study may help explain why children born to women living with HIV often have higher rates of illness and developmental challenges, even when the children themselves are not infected with the virus.

Researchers analyzed 1,426 breast milk samples collected over 18 months from 326 women in Zambia, 288 living with HIV and 38 without HIV, as part of a clinical trial conducted between 2001 and 2008.

Breast milk from women living with HIV contained significantly lower tryptophan levels throughout the entire 18-month study period, with concentrations approximately 50% lower than in milk from mothers without HIV.

This study offers the first metabolic explanation for these health issues and points to potential nutritional interventions to protect vulnerable infants.

“We’ve known for years that children born to mothers living with HIV face greater health challenges, but we didn’t fully understand why,” says corresponding author Dr. Grace Aldrovandi,  professor of Pediatrics and chief of the Division of Infectious Diseases at the University of California, Los Angeles (UCLA), US.

“This study reveals that tryptophan deficiency and altered metabolism may serve as a common denominator explaining the immune, growth, and cognitive differences we see in these children.”

Dr. Nicole Tobin, professor of pediatrics at the UCLA David Geffen School of Medicine and the study’s lead author, adds: “What’s particularly striking is that this metabolic signature persists even when mothers are on effective antiretroviral therapy.”

“That helps explain why these children continue to need extra support despite advances in HIV treatment.”

Key discoveries

Using advanced metabolomics technology, the team measured over 800 different metabolites in the milk samples collected at multiple timepoints, from one week postpartum to 18 months.

They then validated their findings in a second cohort of 47 Haitian women who were receiving antiretroviral therapy.

Plasma measurements revealed lower tryptophan levels in mothers with HIV.Additionally, the team completed a targeted quantitative analysis of tryptophan and kynurenine levels in the mothers’ breast milk and blood plasma. This was done to understand whether the depletion was localized to milk or reflected systemic changes in the mothers’ bodies.

The scientists found that the kynurenine-to-tryptophan ratio in the samples, which indicates immune activation, was significantly elevated at all study visits.

Plasma measurements also revealed lower tryptophan levels in mothers with HIV.

This suggests the reduced tryptophan in their breast milk is due to a systemic shortage — likely from the mother’s poor intestinal absorption — rather than a problem with its transfer into the milk.

The research team also flagged elevated levels of a newly discovered antiviral compound called ddhC in the milk of women living with HIV, along with increased cytosine and dimethylarginine. All of these markers are consistent with chronic viral inflammation and interferon activation.

These metabolic alterations persisted even among HIV-infected mothers receiving antiretroviral therapy with higher immune function.

Upcoming research

The study authors highlight that 1.3 million children globally are born to women living with HIV each year. Even when prescribed effective antiretroviral therapy that prevents HIV transmission, non-infected children still face a 50% increase in mortality in low-income settings, along with increased risks of infections, growth issues, and cognitive disabilities.

Before antiretroviral therapy was introduced, these children had mortality rates that were two to three times higher than those of infants not exposed to HIV. “Understanding why these children remain vulnerable despite not being infected has been a critical gap in maternal and child health research,” underscore the researchers.

They stress that their findings require careful follow-up before they can recommend any nutritional interventions.

The team plans to investigate whether tryptophan supplementation in animal models of chronic viral inflammation can safely improve immune function, growth, and cognitive development without unintended consequences.

Because the inflammatory environment in HIV infection steers tryptophan down pathways that can produce neurotoxic metabolites, the researchers caution that simply replacing tryptophan without modulating these pathways could potentially cause harm.

Future studies will also explore whether infants of mothers living with HIV have reduced systemic tryptophan levels and alterations in the way their bodies process tryptophan.

Findings of the study were published in Nature Communications.