Cellular and Molecular Pediatrics (CMP)

The goal of the CMP group is to explore and understand the mechanisms of disease before and after birth – especially related to infections. We study how milk and microbial factors influence development of cells and organs. This is done using in vitro cell and ex vivo blood and tissue studies from animals and humans. We explain why newborns are susceptiple to infections and how to improve their health status with interventions.

Research focus

Newborn mammals are highly susceptible to infections, especially when born preterm or growth-restricted. Sepsis and necrotizing enterocolitis (NEC) are two important diseases. Optimal nutrition in early life affects health outcome, both short- and long-term.

Closely related to in vivo studies in animals or humans, we use ex vivo and in vitro intestinal, blood and brain cell models to show effects of milk components on epithelial integrity and cellular immunity.  We use advanced -omics techniques (transcriptomics, proteomics, epigenomics) to characterize cells during development and in response to treatments. We also study the milk and microbial factors that are protective or detrimental.

“Coupling information from cell models, animal studies and human trials has a great potential to provide a better mechanistic understanding of diseases in newborns. This leads to better diagnosis, prevention and treatment of important diseases around birth” says Assistant Professor and group leader Duc Ninh Nguyen.

Main findings

Preterm infants are susceptible to sepsis and necrotizing enterocolitis (NEC) but diagnostic markers are lacking. We show that circulating neutrophil-associated proteins and cell-free DNA are involved is associated with sepsis and NEC and may be used as early biomarkers in the future.: Elevated levels of circulating cell-free DNA and neutrophil proteins are associated with neonatal sepsis and necrotizing enterocolitis in immature mice, pigs and infants. DOI:10.1177/1753425917719995

We show that gut bacterial colonization affects the epigenetic programming of intestinal genes related to immunity, vascular integrity and metabolism. This may be critical for short- and long-term gut health in newborns: Early microbial colonization affects DNA methylation of genes related to intestinal immunity and metabolism in preterm pigs. DOI:10.1093/dnares/dsy001 

Dietary lactoferrin supplementation may protect against sepsis and gut inflammation. Using isolated cell studies and preterm pigs, we showed that lactoferrin dose-dependently modulates gut inflammatory responses, as assessed by proteomics: Bovine lactoferrin regulates cell survival, apoptosis and inflammation in intestinal epithelial cells and preterm pig intestine DOI:10.1016/j.prot.2016.03.020

Sponsors

  • Arla Food amba
  • Arla Foods Ingredients
  • Biofiber-Damino
  • Innovation Fund Denmark
  • University of Copenhagen