$3 million grant supports an ambitious effort to improve children’s health around the world

An international team of researchers has received $3 million to support an ambitious effort to understand how early gut development can profoundly shape children's health throughout life.

The funding from the Chan Zuckerberg Initiative will allow scientists at ­the University of Virginia School of Medicine, Boston Children's Hospital, University of Mississippi Medical Center and Pakistan's Aga Khan University to "map" the healthy gut in children ages 5 and younger down to the level of individual cells. The resulting wealth of information will enable the scientific community to design new interventions against various intestinal and nutritional diseases to help children live the healthiest lives possible.

How the gut changes and develops during early childhood is incredibly important for growth, nutrition, cognitive development, our immune system and many other long-term health outcomes. Yet very little is known about these changes in the gut in healthy children at a molecular level. "It is now well established that many aspects of health can be traced back to the first years of life," said Sana Syed, MD, the leader of the UVA study team. "However, what is best for your health might not be what is best for mine. Mapping these changes in early life and how they vary across ancestry and environment will allow us to better understand the diversity of what is 'normal' and also will provide a reference for future investigations into the causes of intestinal diseases."

How gut health affects good health

To better understand what defines the healthy gut, the research team will collect tissue samples from children undergoing endoscopy, a procedure that lets doctors examine the digestive tract, at study sites in Virginia, Massachusetts, Mississippi and Pakistan. These samples collected from diverse groups across study locations will help researchers better understand how the environment, genetics and other factors influence early gut development.

The researchers will initially focus on the upper small bowel but are also collecting tissue samples from other parts of the gastrointestinal tract for future work. They ultimately aim to create a comprehensive "atlas" of the healthy gut in infants and children under 5.

We are now more aware than ever that 'normal' health lies on a spectrum that is influenced by a child's genetics, family ancestry, societal effects and physical environment. Better defining the diversity of 'normal' between healthy patients of different ancestries and environments will have a critical impact on many pediatric gastrointestinal diseases. Is 'normal' different between urban and rural children? Do children from Charlottesville share the same cellular makeup as children from Pakistan? Answering these questions will allow us to provide patient-specific precision medicine to improve childhood health."

Boston Children's Jay Thiagarah, MD, PhD, principal investigator of the study

The project will produce vast amounts of data to fuel future research into how ancestry, geography and environmental factors known as "social determinants of health" affect gut development. The findings will bolster efforts to better battle gut diseases that often strike young children and can cause lifelong harm and suffering.

The researchers will look at the effect of children's exposure to heavy metals in drinking water. This exposure varies in the United States and is particularly high in Pakistan. These metals can affect gut function by altering the microbiome, so the researchers will measure children's exposure by examining the amounts of metals that have accumulated in their toenails.

In particular, the project aims to shed light on rural, minority and disadvantaged communities that have traditionally been underrepresented in such research. In addition to the planned locations in the Unites States and Pakistan, the scientists hope to eventually expand their efforts to include sites in Africa and Asia.

"Diversity and representation in medical research is important to ensuring equitable health benefits for all," says Jocelyn Silvester, MD, PhD, from Boston Children's. "Disease risk and drug efficacy can greatly vary between individuals. Ensuring our studies reflect the diversity of the communities we live in not only improves the accuracy of our results, it also ensures that the research delivers health benefits for all."

The researchers plan to make their findings widely available so that people all over the world can better understand what good gut health looks like. Promoting early gastrointestinal health through new treatments, medical interventions and other steps will help children around the globe live the healthiest, fullest lives possible.

"Addressing health disparities in healthcare and medical research is an urgent need," said Imran Nisar, PhD, principal investigator at Aga Khan University in Karachi, Pakistan. "Through the participation of parents and children across the world, our study will allow us to better understand the 'normal' development of the childhood gut. This study will lay the foundation for developing new therapeutics that work for all ancestries and ethnicities to ensure all children live happy, healthy lives."