Microbiome development in early life: the role of environmental exposures in the ENVIRONAGE birth cohort

Abstract

It is well established that the environment in which we live influences our health. Air pollution exposure has been linked to a higher risk of asthma and inflammatory bowel disorders. In contrast, green space exposure has been associated with lower rates of overweight and improved mental wellbeing. Pregnancy and early childhood are especially critical exposure periods as they represent vulnerable life stages in which the child is in full development. Moreover, exposures during these susceptible periods may have long-lasting health consequences. Nevertheless, there is limited literature on the associations between exposure to air pollution or green space and the microbiome in children. In Chapter 1, we systematically reviewed all available epidemiological, in vitro, and animal evidence on the association between particulate air pollution exposure and intestinal microbiome composition. Given the lack of studies in healthy children, we studied the association between black carbon particles quantified in placental tissue, cord blood, and urine, as biomarkers of pre- and postnatal particulate air pollution exposure, respectively, and the intestinal microbiome composition in four-to-six-year-old children in Chapter 2A. Chapter 2B further explored this relationship in a study with more participants and more detailed information on potential covariables, such as intestinal transit time and diet. In this larger study, particulate air pollution exposure was modeled during the previous year and stool samples were collected from four-to-twelve-year-old children. As the translocation of air pollution-related particles into the intestines is hypothesized as a potential underlying mechanism, we examined whether particles could be visualized in human ileum and colon biopsies of human donors in Chapter 3. Finally, Chapter 4 studied the impact of another type of environmental exposure, i.e., green space around the residence and school combined, on alpha diversity of the skin microbiome in three-to-twelve-year-old children. The key findings of the doctoral research described in this dissertation are summarized in Table 1. In summary, we found that exposure to particulate air pollution was associated with the richness, evenness, and diversity of the intestinal microbiome and the relative abundance of different bacterial families. We noted that these associations were sex-specific, with negative associations in boys and positive trends in girls. Furthermore, we showed the translocation of air pollution-related particles into intestinal tissue, with a higher load in ileum compared to colon. This translocation provides a mechanism for the observed associations between air pollution exposure and the intestinal microbiome. Lastly, exposure to total green and highgrowing green around the residence and school was positively associated with the skin microbiome richness and the relative abundance of four bacterial families.