By Yang Luo
Summary
Chair person: Simon Francis Thomsen
Opponent: Erik Melén
Opponent: Anders Gorm Pedersen
ABSTRACT
Early childhood is a critical period characterized by rapid growth, development, and vulnerability to various health conditions. Among these, infectious diseases are particularly concerning. Each year, respiratory and gastrointestinal infections rage around the world, affecting the health of hundreds of millions of children. While exposure to pathogens may trigger these infections, host factors, such as nutrition, immunity, and genetics, determine disease susceptibility, manifestation, and progression. This thesis aims to examine the roles of these host factors in infectious diseases during early childhood and to explore potential preventive and intervention strategies.
In Paper I, we demonstrated that prenatal supplementation of n-3 long-chained polyunsaturated fatty acid (n-3 LCPUFA) and a high dose of vitamin D can reduce the risk of croup in the offspring during their early years. Both n-3 LCPUFA and high-dose vitamin D individually demonstrated a significant risk reduction, without any evidence of interaction between the supplements.
In Paper II, we examined the association between genetically determined fucosyltransferase-2 (FUT2) secretor status and the risk of gastroenteritis and gut microbiota in early life. The study found both maternal and child secretor status were independently associated with increased risk of gastroenteritis. Maternal status was particularly associated in the first year and child status in the second year of life after starting in daycare. Similarly, maternal secretor status significantly influenced children’s gut microbiota composition in early life, at 1 week and 1 month, whereas children’s secretor status exerted more influence at 1 year. Microbiota associations were largely independent of gastroenteritis risk, except from abundance of Bacteroides vulgatus, which seemed to counteract increased risk of gastroenteritis in secretor children.
In Paper III, we observed that genetic susceptibility to an increased neutrophil activation in terms of high levels of blood neutrophil count was associated with an increased risk of severe asthma exacerbations in early childhood. This predisposition also correlated with an enhanced type 17 immune response to viral infections. Furthermore, such increased neutrophil immune response in early life might increase risk of viral respiratory illnesses and asthma development, emphasizing the critical interplay between genetic susceptibility and immune responses in early respiratory health.
In Paper VI, A Genome-Wide Association Study (GWAS) identified three genetic loci – CDHR3, OAS1, and ORMDL3- linked to susceptibility to the common cold in early childhood, with temporal analyses indicating age-dependent effects of these genes. These results improve understanding of the host factors involved in susceptibility to viral infections in early life, offering insights for improved disease management and prevention.
Collectively, these studies underscore the significant influence of host factors—both genetic and nutritional—on childhood infectious diseases. Understanding these interactions can pave the way for targeted interventions and preventive strategies.
