Martin Steen Mortensen:
The human microbiota in early life. Initial colonization and development

Date: 29-01-2016    Supervisor: Søren J. Sørensen & Waleed Abu Al-Soud

The bacteria that colonize the human body, our microbiota, can influence our health, both positively and negatively. The importance and functions of the microbiota in our intestinal tract have been the focus of several research projects and are widely published. However, there are great gaps in our knowledge concerning microbiota composition, development and function in other areas of human body. Lack of knowledge about the microbiota development in the airways is an example of such a deficiency.

The work presented in this PhD thesis is based on the vast sample collection of the COPSAC2010 cohort, with 700 mother-infant pairs. The objectives were to perform a detailed examination of the mothers’ vaginal microbiota, describe the early composition and development of the microbiota in the airways of their infants, and determine whether the infants’ microbiota are affected by that of their mothers or not.

Manuscript I examines the composition and stability of vaginal microbiota, as well as how the mothers’ microbiota contribute to the early bacterial colonization of their infants. In this study, we first confirmed that the vaginal microbiota of the women in the COPSAC2010 cohort represent the already well-defined community state types. In addition, we showed that for most women the vaginal microbiota at week 24 of pregnancy is similar to the microbiota twelve weeks later at week 36. The manuscript also contains a novel description of how mothers’ vaginal microbiota has affected the microbiota of their infants one week after birth. The results show that delivery mode is important for bacterial transfer from mother to infant.

Manuscript II focuses on the microbiota in lower airways aspirates, collected from infants one week, one month and three months after birth. The manuscript explores the differences in the microbiota composition at the three time points, examining as well the time dependent changes of each infant separately. One week after birth, Staphylococcus, traditionally associated with skin microbiota, is dominating the microbiota, but as time passes, bacteria normally found in the airways (e.g. Streptococcus and Moraxella) become increasingly dominant. By defining the core microbiota for each infant, the manuscript shows that 69% of the microbiota, three months after birth, represent bacteria that were present at both one week and one month after birth. Lastly, the manuscript describes how the microbiota can be separated into five distinct pneumotypes: four having a single dominating genus and one without a common defining genus.

The last manuscript, Manuscript III, compares the microbiota descriptions obtained by classical identification using culturing and high throughput sequencing of amplified 16S rRNA. Weaknesses and strengths of both methods are presented; the comparison has shown that sequencing gives a more detailed representation, as more bacteria, both types and number, can be identified. However, the sequencing approach used in this study lacks of resolution. The manuscript concludes that sequencing is almost ready for clinical use, as disadvantages of the method can be solved by using a combination of techniques that have been shown to work separately.

The results presented in the manuscripts of this PhD thesis have strengthened current knowledge of our microbiota and have contributed with novel research to improve the understanding of the microbiota development during the early period of life.