Research team introduces new tool to boost battle against childhood undernutrition

A new tool developed at the University of Virginia School of Medicine is expected to help doctors and scientists better understand and overcome childhood undernutrition that contributes to almost half of all deaths of children under 5.

The research model created by UVA's Carrie A. Cowardin, Ph.D., and colleagues provides a more sophisticated way to study the effects of undernutrition on the microbiome, the microbes that naturally live inside the gut, and in turn, on growth and the immune system.

The paper is published in the journal Microbiome.

Scientists routinely study the many complex interactions within the microbiome by taking samples from the human microbiome and moving them into lab mice. But Cowardin and colleagues found that they could significantly improve the effectiveness of that model by introducing the microbes when the mice were very young, before they had been weaned. This new model of "intergenerational colonization," they determined, better mimicked the effect of undernutrition during early childhood.

"We believe this new model will help us investigate many of the major challenges facing undernourished children, including higher rates of infection and changes in cognitive development," said Cowardin, part of UVA's Department of Pediatrics. "Our current studies are using this system to identify specific microbes that impact development, with the goal of using these microbes as therapies to promote healthy growth. "

Undernutrition and the microbiome

Using Cowardin's new model, the researchers found that unweaned mice that were given microbes derived from children with impaired growth also suffered stunted growth. Further, the young mice developed immune system responses similar to those seen in human children. But when the microbes were given to mice later in life, the effects were much less similar to what was seen in humans.

That suggests Cowardin's new approach offers a better way to study childhood undernutrition. Further, the results align nicely with prior research suggesting that infancy is a critical period that shapes the health and strength of the immune system throughout life, the researchers say.

The new model, Cowardin said, should help scientists better understand the underlying biological causes of stunted growth and other harmful effects of undernutrition in developing countries. That understanding will advance efforts to develop new approaches to prevent those effects and help children live longer, healthier lives.

"We hope this work also allows us to answer fundamental questions about how the microbiome interacts with our own cells to shape the course of development," Cowardin said. "Growth stunting due to undernutrition is a really difficult problem facing global child health, and the lessons we learn will likely apply to many other conditions as well."