PhD defence by Tatiana Siegler Lathrop

Principal supervisor:

• Professor Ioannis S. Chronakis

Co-supervisor:

• Associate Professor Rochellys Heijtz Diaz

Examiners:

• Associate Professor Matin Steen Mortensen, Technical University of Denmark
• Professor Philip W. J. Burnet, University of Oxford
• Professor Karen Angeliki Krogfelt, Roskilde University

Chairperson at defence:

• Associate Professor Ana Mendes

Resume
The first years of life are a crucial time for brain development, and growing evidence shows that the gut microbiota, the community of bacteria and other microbes along with all the molecules they produce living in the gut, play an important role in shaping how the brain and therefore behavior develops.

This PhD thesis explores how changes in the gut microbiota during pregnancy and early life can influence long-term behavior and brain health of offsprings. In a series of mouse studies, we tested whether giving mothers probiotics (beneficial bacteria) during could improve outcomes for their offspring. We found that prenatal probiotic exposure had effects on the gut, the brain and the behavior of the offspring mice. The behavior of offspring from mothers who have been exposed to probiotics during pregnancy showed increased social interactions and decreased anxiety behavior.
These changes were linked to specific brain and immune genes changes, some of which are essential to regulate stress and social behaviors. Interestingly, many of these effects were stronger in male offspring, especially the behavioral changes, compared to their female siblings, highlighting important sex difference in how the gut microbiota and the brain interact. We tested different types of probiotics and found that specific strains and combinations of probiotics have slightly different target effects in the brain.

To connect these findings to human development, we studied infant data from a bigger study called ELICIT. Small molecules made by the body and the gut microbiota called metabolites were measured in blood and urine of infants. We discovered patterns that linked to brain growth and cognitive development during the first two years of life. Key nutrients such as the molecule choline and certain fats and bile acids also showed differences between boys and girls.

Together these studies confirm and further elucidate the deep connection between the gut and the brain from conception to the very start of life. Supporting the gut microbiota during pregnancy and infancy offers new ways to promote healthy brain development and prevent developmental difficulties throughout life.

A copy of the PhD thesis is available for reading at the department.