Breast milk nutrient boosts long-term immune system development

Trans-vaccenic acid (TVA), the most abundant trans fatty acid found in human breast milk, helps boost immune system development and has long-lasting effects on immune system health in mice, according to a new study by researchers from the University of Chicago.

The study, published this week in Science, showed that nursing female mice fed a diet enriched with TVA passed the nutrient to their pups, leading to increased production of immune cells during early development. Genetic analyses also showed that TVA exposure during breastfeeding reprogrammed immune cells to improve responses to pathogens. Mice that were nursed on TVA-enriched milk responded faster to infections with viruses or common bacteria, even into adulthood.

Jing Chen, PhD, the Janet Davison Rowley Distinguished Service Professor of Medicine at UChicago and one of the senior authors of the new studyIt's common knowledge that breastfeeding is important for neonatal immune development and overall health, but breast milk is so complex that it seems almost impossible that one single molecule would be sufficient to change a baby's immune development. So, it was very surprising to see that during this crucial stage of development, one nutrient derived from the mother's diet and delivered through breastfeeding has such a tremendous effect."

Long-term immune imprinting

In a series of mouse experiments, the team fed nursing mothers a diet enriched with TVA. The nutrient was passed on to their pups through breast milk, where it promoted the development of a broader and more effective immune cell population, particularly CD4+ T cells that are important for adaptive immunity.

Interestingly, this advantage appeared only when mice were exposed to TVA during breastfeeding. Pups that were exposed to TVA via the mothers' diet during pregnancy but were then nursed by a foster mother who was not on a TVA-rich diet did not have these improved responses to infection.

"We saw that only postnatal exposure to TVA through breastfeeding is important to train the neonatal T cells, and this can have long-lasting imprinting effects," Chen said. "Even in adulthood, when we challenged the mice with influenza, the ones that were exposed to higher TVA levels during breastfeeding responded better when battling the infection."

They found that higher TVA levels in breast milk were closely linked to higher TVA levels in infants' blood. In preterm infants, levels of circulating TVA correlated with similar shifts in immune responses to those the researchers saw in mice. Higher TVA levels in human breast milk were also associated with reduced risk of bronchopulmonary dysplasia, a chronic inflammatory lung disease that affects premature infants with underdeveloped lungs and increased susceptibility to respiratory infection.

'A question that has huge health impact'

Chen said working with partners like He, with his extensive experience with RNA sequencing and epigenetic analysis, and Claud, with her expertise on early infant development, was crucial to the success of this study. "This was truly 'team science.' It definitely reflects the great collaborative environment here at UChicago," he said. "That's our strong suit, with three different departments working together to address a question that has huge health impact."

With multiple studies now showing the immune benefits of TVA, particularly in the early-life period, Chen said he hopes there will be more research on the possibilities for supplementing diets with TVA during pregnancy and breastfeeding or adding it to infant formula. The team wants to investigate other fatty acids and nutrients found in breast milk to understand their benefits as well.

"There are close to 40 fatty acids in total in breast milk, along with hundreds of other components," Chen said. "So, I think it's safe for us to say that we believe there could be additional fatty acids and nutrients that can do something similar."

The study, "Maternal trans-vaccenic acid shapes neonatal T cell development and early-life immune imprinting," was supported by the National Institutes of Health, the National Cancer Institute, the Ludwig Center at UChicago, the Sigal Fellowship in Immuno-oncology, and the Harborview Foundation Gift Fund.

Additional authors include Hao Fan, Zhong Zheng, Kaitlyn Oliphant, Jiacheng Li, Cheng Wei Ju, Brandon Trandai, Jiayi Tu, Freya Q. Zhang, Rukang Zhang, Zhicheng Xie, Chunzhao Yin, Chufan Cai, Megan S. Kennedy, Tess McNeely, Candace Cham, Robert B. Hamanaka, Gökhan M. Mutlu and Eugene B. Chang from UChicago; Ryan Mack and Jiwang Zhang from Loyola University Chicago; Lei Dong from the University of Texas Southwestern Medical Center; Rui Su from the Beckman Research Institute of City of Hope; Camilia R. Martin from Weill Cornell Medicine; Brian T. Layden from the University of Illinois Chicago; and Hongbo Chi from St. Jude Children's Research Hospital.

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University of Chicago

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