Abstract

The composition of human breast milk is highly variable, and it can be influenced by genetics, diet, lifestyle, and other environmental factors. This study aimed to investigate the impact of geographical location and mode of delivery on the nuclear magnetic resonance spectroscopy (NMR) metabolic profile of breast milk and its relationship with the milk microbiome. Human milk metabolic and microbiota profiles were determined using NMR and 16S rRNA gene sequencing, respectively, in 79 healthy women from Finland, Spain, South Africa, and China. Up to 68 metabolites, including amino acids, oligosaccharides, and fatty acid-associated metabolites, were identified in the milk NMR spectra. The metabolite profiles showed significant differences between geographical locations, with significant differences (p < 0.05) in the levels of galactose, lacto-N-fucopentaose III, lacto-N-fucopentaose I and 2-fucosyllactose, 3-fucosyllactose, lacto-N-difucohexaose II, lacto-N-fucopentaose III, 2-hydroxybutyrate, 3-hydroxybutyrate, proline, N-acetyl lysine, methyl-histidine, dimethylamine, kynurenine, urea, creatine and creatine phosphate, formate, lactate, acetate, phosphocholine, acetylcholine, LDL, VLDL, ethanolamine, riboflavin, hippurate, spermidine, spermine and uridine. Additionally, the effect of caesarean section on milk metabolome was dependent on the geographical region. Specific interrelations between human milk metabolites and microbiota were also identified. Proteobacteria, Actinobacteria, and Bacilli were most significantly associated with the milk metabolites, being either positively or negatively correlated depending on the metabolite. Our results reveal specific milk metabolomic profiles across geographical locations and also highlight the potential interactions between human milk’s metabolites and microbes.

Highlights

  • The cornerstone of healthy growth and development in children is breast feeding, since breast milk offers myriad physiological advantages when compared to other sources of nutrition.the optimal model of infant feeding is the healthy breastfed child [1]

  • The particles detected in milk have similar nuclear magnetic resonances (NMR), physicochemical properties and mobility than those lipoproteins detected in plasma

  • We found a group of metabolites to be positively correlated with Gammaproteobacteria, including lactate, creatine, proline, lacto-N-fucopentaose I, and 2-fucosyllactose VLDL, as well as negatively correlated with Alpha- and Betaproteobacteria, and Bacilli

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Summary

Introduction

The cornerstone of healthy growth and development in children is breast feeding, since breast milk offers myriad physiological advantages when compared to other sources of nutrition.the optimal model of infant feeding is the healthy breastfed child [1]. The cornerstone of healthy growth and development in children is breast feeding, since breast milk offers myriad physiological advantages when compared to other sources of nutrition. Breast milk contains many biologically active compounds, such as growth factors, antimicrobial and immune-enhancing substances, oligosaccharides (HMOs), as well as a diverse and rich bacterial community [7,8,9,10]. The composition of human breast milk is determined by genetic factors, lifestyle, diet, and the age of the mother [11,12]. While some components of human milk appear to be relatively stable across different locations, some, such as polyunsaturated fatty acids, vary according to the mother’s diet [9,14], while others, such as polyamines [15], HMOs [16], and milk bacteria [9,17], seem to vary depending of multiple factors. The complex interactions between the constituents of milk, the biological impact, and the consequences for the infant’s health in the short- and long-term remain unclear

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