Breast Milk Fatty Acid Shapes Immune Development in Mice

In a new study published in Science titled, “Maternal trans-vaccenic acid shapes neonatal T cell development and early-life immune imprinting,” researchers from the University of Chicago have found that trans-vaccenic acid (TVA), the most abundant trans fatty acid in human breast milk, helps boost immune system development in mice. 

Nursing female mice that were fed a diet enriched with TVA passed the nutrient to their pups, leading to increased production of immune cells during early development. Genetic analyses 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. 

“It’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,” said Jing Chen, PhD, professor of medicine at UChicago and co-corresponding author on the study. “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.” 

TVA is a long-chain fatty acid found in meat and dairy products from grazing animals such as cows and sheep. The human and mouse body must obtain TVA through diet.  

Pups who were nursed by mothers with a diet enriched with TVA demonstrated a broader and more effective immune cell population, particularly CD4+ T cells that are important for adaptive immunity. Mice raised on TVA-enriched breast milk responded more quickly and had higher survival rates when exposed to the flu virus or Salmonella. 

“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.” 

The team also analyzed TVA levels in breast milk and blood samples from human nursing mothers and infants. 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 seen 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. 

Chen hopes for more research on the possibilities for supplementing diets with TVA during pregnancy and breastfeeding, or infant formula. The team will also investigate additional fatty acids and nutrients found in breast milk to understand their benefits. 

“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.” 

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