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Infant rhesus monkeys that are breast fed develop distinct immune systems from those that are fed formula from a bottle, a new study shows.

While researchers expected different diets would promote different intestinal bacteria (microbiota), they were surprised at how dramatically these microbes shaped immunologic development. Specifically, breast-fed macaques had more “memory” T cells and T helper 17 (TH17) cells, which are known to fight salmonella and other pathogens.

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The differences persisted for months after the macaques had been weaned and placed on identical diets, indicating that variations in early diet may have long-lasting effects.

“We saw two different immune systems develop: one in animals fed mother’s milk and another in those fed formula,” says Dennis Hartigan-O’Connor, assistant professor in the medical microbiology and immunology department at University of California, Davis and a scientist at the California National Primate Research Center.

“But what’s most startling is the durability of these differences. Infant microbes could leave a long-lasting imprint on immune function.”

Big differences at six months

Previous research has highlighted the relationship between breast milk, microbiota, and the developing immune system. For example, sugars in breast milk help grow specific bacteria, which in turn support certain immune cells.

The new study, published in Science Translational Medicine, is an important step towards understanding how these separate pieces link together and how they might influence the immune systems response to infections or vaccinations.

Macaques are born with virtually no TH17 cells, and must develop them during the first 18 months of life. Some macaques develop large TH17 populations, while others have few of these cells. This could profoundly affect the animals’ ability to fight infection, particularly SIV, the simian strain of HIV.

To understand this variability, the investigators followed six breast- and six bottle-fed rhesus macaques from age five months to 12 months. At six months, they found significant differences in the two groups’ microbiota.

Specifically, the breast-fed macaques had larger numbers of the bacteria prevotella and ruminococcus, while the bottle-fed group had a greater abundance of clostridium. Overall, the microbiota in breast-fed macaques was more diverse than in the bottle-fed group.

Gut microbes

The big surprise came when examining their immune systems. By 12 months, the two groups showed significant contrasts, with the differences centered on T cell development. The breast-fed group had a much larger percentage of experienced memory T cells, which are better equipped to secrete immune defense chemicals called cytokines, including TH17 and interferon-producing cells.

“This is the first time researchers have shown that these immunologic characteristics may be imprinted in the first new months of life,” says Amir Ardeshir, the study’s first author. “Our study suggests that the gut microbiota present in early life may leave a durable imprint on the shape and capacity of the immune system, a programming of the system if you will.”

Further investigation may have identified chemicals that drive these differences. For example, arachidonic acid, which stimulates the production of TH17 cells and is found in macaque breast milk, was tightly linked to TH17 cell development. Previous studies have suggested it can influence T cell development. The researchers caution that these chemicals must be tested in larger studies to understand their effects.

While this research provides a fascinating window into immune cell development in macaques, it doesn’t prove the same mechanisms exist in people, The lab is planning similar studies in humans to test that hypothesis. In addition, this study does not prove a link between breastfeeding and better health.

“There’s a developmental shape to the immune system that we don’t often consider,” Hartigan-O’Connor says. “It’s dramatic how that came out in this study. There’s a lot of variability in how both people and monkeys handle infections, in their tendency to develop autoimmune disease, and in how they respond to vaccines. This work is a good first step towards explaining those differences.”

Other researchers from UC Davis and from UC San Francisco are coauthors of the study. The National Institute of Allergy and Infectious Diseases, the Bill and Melinda Gates Foundation, and the National Institutes of Health provided funding.

Source: UC Davis