Human milk is a unique tissue specifically evolved to nourish the developing infant. Accumulating evidence suggests that infant health is impacted by a balanced composition of highly abundant sugars, known as human milk oligosaccharides (HMOs). The challenge in defining such a balance lies in the immense number and diverse variation in HMO structures. Aside from the expression of fucosyltransferases, little is known about the basis of HMO variability between mothers. Therefore, this thesis used the INSPIRE and CHILD mother-infant cohorts to investigate how HMO profiles compare geographically between healthy women and what maternal characteristics may be associated with this variability. Additionally, we used a third set of samples to begin to investigate the influence of HMOs, in utero, by confirming their presence in the amniotic fluid.
HMOs were isolated from human milk samples and analyzed by rapid high-throughput HPLC to determine overall HMO composition and associations between HMOs and maternal characteristics. MALDI-TOF MS was used to further confirm HMO structures in both urine and amniotic fluid.
We provide data on what can be considered normal with respect to HMO variation and composition between healthy populations of women. We also show that certain maternal characteristics including weight, BMI, parity, secretor blood group status, and the duration of lactation influence HMO composition. Additionally, we present a novel finding that certain HMOs are present in amniotic fluid. Together these results offer new avenues towards understanding the biological relevance of HMOs, as well as defining HMO balance and what factors may be of importance.