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 as well as immunometabolic drugs influence cell and organ development and resistance against infections. This is done using in vitro cell and ex vivo blood and tissue studies from animals and humans with and without infections. We explain why newborns are susceptiple to infections and how to improve their health status with interventions.
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 and gut colonization 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 or drugs 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 as well as drugs (antibiotics, immunometabolic drugs) 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 Associate Professor and group leader Duc Ninh Nguyen.”
Preterm infants are often born with prenatal inflammation, e.g. chorioamnionitis (CA), which may separately or together with the reduced gestational age at birth to affect neonatal immune development. We show in a recent established model of preterm pigs born with CA that CA induces innate immune activation at birth and suppresses Th1 polarization during early life. This may explain that preterm infants with CA have increased risks of neonatal sepsis. Prenatal inflammation suppresses blood Th1 polarization and gene clusters related to cellular and energy metabolism in preterm newborns. DOI:10.1096/fj.201902629R
Infants born preterm or small for gestational age (SGA, due to fetal growth restriction) has increased risk of neonatal infection, but it remains unclear if the co-occurrence of both events affect infection resistance during early life, relative to one single event. Using preterm pigs as a model, we now show that preterm pigs with fetal growth restriction have diminished immune responses to exogenous challenge at birth, leading to more severe sepsis induced by systemic infection as well as poorer bacterial clearance, relative to the counterparts with appropriate birth weight. Our results urge the need of better care for SGA preterm infants. Impaired neonatal immunity and infection resistance following fetal growth restriction in preterm pigs. DOI: 10.3389/fimmu.2020.01808/full
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
- Arla Food amba
- Arla Foods Ingredients
- Innovation Fund Denmark
- University of Copenhagen
|Bering, Stine Brandt||Associate Professor||+4535331092|
|Bæk, Ole||PhD Fellow||+4535330104|
|Muk (Mudi), Tik||Postdoc||+4535332272|
|Nguyen, Duc Ninh||Associate Professor||+4535333250|
|Spiegelhauer, Malene Roed||Research Assistant||+4535324693|
|Wu, Ziyuan||PhD Student|
|Yang, Lin||PhD Student|