Research has revealed that breastmilk consumption can help promote healthy brain development in infants, but not all infants are able to receive breastmilk due to a number of factors. A newly-awarded $638,000 federal grant is funding a Husker research initiative on the subject.

University of Nebraska–Lincoln scientists will analyze gut microbiome function, looking to see how mice process milk nanoparticles whose biological signaling appears to have important benefits for cognitive development. Ultimately, research in this field could lead to development of new infant formulas fortified with specific nutritional enhancements.

The U.S. Department of Agriculture National Institute of Food and Agriculture has approved the grant to the laboratory of Janos Zempleni, Willa Cather Professor of molecular nutrition in the Department of Nutrition and Health Sciences at Nebraska. The project will also involve the Nebraska Center for the Prevention of Obesity Diseases, of which Zempleni is director.

The foundation for the project is that milk contains large quantities of natural nanoparticles known as exosomes, while the quantity in infant formula is negligible. Milk exosomes are biologically important because they help facilitate cellular communication affecting organ function. Bacteria in the gut microbiome — the complex intestinal network of microorganisms processing digested food — absorb the milk exosomes.

Zempleni and his Husker colleagues will pursue a particular hypothesis: Gut bacteria, they speculate, transmit milk exosome-based signals to the brain through the bacteria’s production of signal-facilitating nanoparticles known as outer-membrane vesicles (OMVs) and cytoplasmic membrane vesicles (CMVs). In pioneering work, the Husker researchers will comprehensively study the details of that process and its possible effects on cognitive development.

The NIFA-funded project will examine how the bacteria’s absorption of the milk exosomes changes the amount and content of OMVs and CMVs produced by the bacteria. Those nanoparticles carry biological signaling material, transmitting it to cells. Husker scientists then will examine the activity of OMVs and CMVs in traveling through the body for possible absorption by organs, including the brain.

Several years ago, preliminary research findings by Zempleni and his Husker colleagues involving mice indicated strong beneficial effects milk exosomes apparently have on brain function. In that project, Zempleni said, “young mice receiving a milk exosome-sufficient diet performed nine times better than mice fed a milk exosome-depleted diet in a test of spatial learning and memory.” The test involved a specially-designed maze.

That research project also found that mice fed the milk exosome-depleted diet had five times greater susceptibility to seizures when the brain was stimulated using kainic acid.

In this new project, the scientists will seek to find answers on three key matters:

• Effects on gut microbiome bacteria. Using laboratory-based, mice-focused research, the scientists will study how the bacteria’s absorption of milk exosomes alters the quantity and content of bacterially produced OMVs and CMVs.
• Absorption from the gut microbiome.

“We don’t know if these OMVs and CMVs are bioavailable. That means, are they absorbed from the gut, or are they not absorbed?” Zempleni said.

• Destination of these signal-transmitting nanoparticles. The NU scientists will look to see where in the body the OMVs and CMVs go.

“Do they go to the brain?” Zempleni said. “And, as a hypothesis, do they make a difference as far as cognitive development is concerned?”

This project will be the latest by Zempleni’s lab as it pursues wide-ranging nutrition science research involving milk, the microbiome and human health. Another notable NIFA-funded project for the lab, for example, is its research into milk as a potential vehicle delivering cancer-fighting therapeutics to the brain. This research can help fill what USDA and the National Institutes of Health have described as a significant knowledge gap involving the scientific details of milk composition and its possible effects on human health.

Zempleni is a fellow of the American Association for the Advancement of Science and winner of the Institute of Agricultural and Natural Resources’ 2015 Omtvedt Innovation Award. Last year, he made an invited presentation on novel functions of milk exosomes to members of the U.S. House and Senate Agriculture Committees.

“If you look at the clinical and epidemiological data, there is a lot of evidence suggesting that milk consumption in infants, compared to formula, has beneficial effects on brain function and brain health,” Zempleni said. “So, the ultimate goal is maybe to arrive at a way to develop improved infant formulas, basically exosome-fortified formulas.”

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