USDA funding supports Zempleni research on breastmilk consumption and brain development

03 Feb 2023     By Geitner Simmons - IANR Media

Scientific findings this century have revealed significant indications that breastmilk consumption can help promote healthy brain development in infants. A newly awarded $638,000 federal grant funds 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’s National Institute of Food and Agriculture (NIFA) has approved the  grant to the laboratory of Janos Zempleni, the Willa Cather Professor of molecular nutrition in UNL’s Department of Nutrition and Health Sciences. 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 UNL 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 OMVs and 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 (outer-membrane vesicles) and CMVs (cytoplasmic membrane vesicles) produced by the bacteria. Those nanoparticles carry biological signaling material, transmitting it to cells. UNL 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 UNL colleagues involving mice indicated strong beneficial effects milk exosomes apparently have on brain function. In that project, Zempleni says, “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 Husker 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 Husker 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 says.
• Destination of these signal-transmitting nanoparticles. The UNL scientists will look to see where in the body the OMVs and CMVs go. “Do they go to the brain?” Zempleni says. “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 UNL 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 Sciences 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 says. “So, the ultimate goal is maybe to arrive at a way to develop improved infant formulas, basically exosome-fortified formulas.”

As with so much of scientific research, the process ahead will be an incremental one, as researchers conclude one set of findings, then another. “We have a long way to go” Zempleni says, “but we have to go one step at a time, then look at the next step.”