Advanced Characterization of Biofunctional Human Milk Oligosaccharides by Mass Spectrometry and Complementary Methods

Abstract

CHAPTER XII Zusammenfassung in deutscher Sprache CHAPTER XIII Curriculum Vitae, List of Publications & Acknowledgements CHAPTER I Introduction and Thesis Outline 10 Chapter 1Furthermore, metabolites contained in human milk have been compared on a worldwide basis by Gay et al. 2018 [19]. Other animal milks could also serve as future alternative macronutrient sources for infant milk formula production. A recent side by side comparison of macronutrients has been compiled for human, goat, cow and sheep milk by van Leeuwen et al. in 2020 [20] with a specific focus on goat milk oligosaccharides.The composition of human milk is relatively conserved across populations but not static. The dynamic adaptation of human milk composition between parturition and the following course of lactation (which may last up to 2 years pp [21]) is believed to be tailored to the changing needs of the infants in this period [22]. To better address and categorize distinct milk qualities resulting from different stages of lactation, colostral milk ~1-5 days post partum (pp)), transitional milk (~ 6-15 days pp) and mature milk (> 15days pp) are generally distinguished. HUMAN MILK OLIGOSACCHARIDES AND THEIR FUNCTIONAL RELEVANCEBeyond well-known nutritional properties of HM macronutrients, many individual human milk compounds may exert additional biological functions which may be crucial for the healthy development of the infant [6]. In this context, and although present in much lower levels, peptides [23, 24] and glycoconjugates (e.g. glycoproteins and glycolipids) [25] gain more and more scientific interest [26]. Even more, human milk oligosaccharides (HMOs) seem to be a promising class of human milk constituents as they may confer many intriguing functional properties of which some are likely to facilitate or influence healthy development of neonates [27][28][29][30][31]. The increasing commercial availability of authentic HMO-structures via novel biotechnological production processes [32] facilitated the addition of individual HMOs like 2'-Fucosyllactose (2'-FL) [33, 34] and Lacto-N-neotetraose (LNnT) [35] to infant milk formula (IF). The safety of the former and additional HMOs like e.g. 3'-Sialyllactose (3'-SL) and 6'-Sialyllactose (6'-SL), which are all considered as "novel food" ingredients with respect to infant formulae (IF), has been investigated in several studies [37][38][39] and approved by various food safety authorities such as the European Food Safety Authority (EFSA) [39][40][41][42][43][44] or the United States Food and Drug Administration (FDA).In literature, distinct structure-function relationships have already been attributed to several HMOs and HM glycans, but for the vast majority of HMOs early life functions still need to be explored. The already known beneficial properties of HMOs, which are non-digestible in the upper gastrointestinal tract [45], range from direct antiinfective [46] and immunomodulatory effects to indirect influences on the hosts