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Open Access Publications from the University of California

Scholarly Works (6 results)

  • Thesis
  • Peer Reviewed
UC Davis Electronic Theses and Dissertations (2021)

Breast milk is the gold standard for infant nutrition because in addition to nutrients, it also provides bioactive components that benefit the health of the developing infant. Infants under six months are recommended to be exclusively breastfed (EBF). Infant feeding practices determined by parental recall methods have been reported to have discrepancies when compared with results measured by the deuterium dose-to-mother (DTM) technique. However, the DTM method is limited by its high workload of sample collection and its validity outside the sample collection window. Finding markers of infant feeding practice using a readily accessible biological sample (such as urine or feces) is a promising novel approach to determine infant feeding practices.Breast milk is dynamic and its composition is impacted by many factors among which maternal secretor status and Lewis blood type impacts the levels of several human milk oligosaccharides (HMOs). Previous research has demonstrated the influence of maternal HMO phenotype on the infant gut microbiome. However, these studies used recall methods to determine infant feeding practice and the sample size used were relatively small. Therefore, it is important to illustrate this impact in a larger infant population whose feeding practice were determined objectively. This dissertation investigates the impact of maternal HMO phenotype on the milk metabolome, infant metabolism and gut microbiome, and seeks to develop metabolic biomarkers of feeding practice from samples of infant feces and urine. Chapter 1 reviews the compositional differences between human milk and infant formula, as well as the recent efforts to narrow the gap between the two. Chapter 2 demonstrates the impact of maternal secretor status and Lewis blood type on breast milk metabolome. Fold change analysis showed that the non-secretor (Se-) Lewis negative (Le-) milk had major differences in free fatty acids, free amino acids, and metabolites related to energy metabolism. Chapter 3 shows the impact of maternal secretor status on the infant fecal metabolome and gut microbiome. Maternal secretor status did not alter the within-community (alpha) diversity, between-community (beta) diversity, or the relative abundance of bacterial taxa at the genus level. However, differences in infant gut microbial fermentation products were observed with succinate, amino acids and their derivatives, and 1,2-propanediol. Chapters 4 and 5 develop and validate metabolic biomarkers for the discrimination between EBF and nonexclusively breastfed (non-EBF) infants using fecal and urine samples, respectively. Metabolites with excellent prediction performance (area under the receiver operating curve (AUC) above 0.8) were identified as biomarkers, and these included HMOs, short-chain fatty acids, amino acids (AAs) and organic acids in infant feces, and AA derivatives, nicotinamide-adenine dinucleotide degradation products, and metabolites from dietary sources and/or host-microbial co-metabolism in infant urine. This work provides new insights into the impact of maternal secretor status and Lewis blood type on the breast milk metabolome, as well as a further knowledge on how maternal secretor status influences the EBF infant gut metabolome and microbiome. The results in this study pave the road to a deeper understanding of how the choice of feeding practices impacts infant metabolism and the gut microbiome, and demonstrates the power of utilizing metabolic biomarkers as a novel approach to determine infant feeding practice.

    Cover page: Metabolomic markers of exclusive breastfeeding in infants
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2023)
    Maternal secretor status has been shown to be associated with the presence of specific fucosylated human milk oligosaccharides (HMOs), and the impact of maternal secretor status on infant gut microbiota measured through 16s sequencing has previously been reported. None of those studies have confirmed exclusive breastfeeding nor investigated the impact of maternal secretor status on gut microbial fermentation products. The present study focused on exclusively breastfed (EBF) Indonesian infants, with exclusive breastfeeding validated through the stable isotope deuterium oxide dose-to-mother (DTM) technique, and the impact of maternal secretor status on the infant fecal microbiome and metabolome. Maternal secretor status did not alter the within-community (alpha) diversity, between-community (beta) diversity, or the relative abundance of bacterial taxa at the genus level. However, infants fed milk from secretor (Se+) mothers exhibited a lower level of fecal succinate, amino acids and their derivatives, and a higher level of 1,2-propanediol when compared to infants fed milk from non-secretor (Se-) mothers. Interestingly, for infants consuming milk from Se+ mothers, there was a correlation between the relative abundance of Bifidobacterium and Streptococcus, and between each of these genera and fecal metabolites that was not observed in infants receiving milk from Se- mothers. Our findings indicate that the secretor status of the mother impacts the gut microbiome of the exclusively breastfed infant.
      Cover page: Impact of milk secretor status on the fecal metabolome and microbiota of breastfed infants.
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2024)
      Human milk provides bioactive compounds such as milk fat globules (MFGs), which promote brain development, modulate the immune system, and hold antimicrobial properties. To ensure microbiological safety, donor milk banks apply heat treatments. This study compares the effects of heat treatments and homogenization on MFGs physicochemical properties, bioactivity, and bioavailability. Vat pasteurization (Vat-PT), retort (RTR), and ultra-high temperature (UHT) were performed with or without homogenization. UHT, RTR, and homogenization increased the colloidal dispersion of globules, as indicated by increased zeta potential. The RTR treatment completely inactivated xanthine oxidase activity (a marker of MFG bioactivity), whereas UHT reduced its activity by 93%. Interestingly, Vat-PT resulted in less damage, with 28% activity retention. Sialic acid, an important compound for brain health, was unaffected by processing. Importantly, homogenization increased the in vitro lipolysis of MFG, suggesting that this treatment could increase the digestibility of MFG. In terms of color, homogenization led to higher L* values, indicating increased whiteness due to finer dispersion of the fat and casein micelles (and thus greater light scattering), whereas UHT and RTR increased b* values associated with Maillard reactions. This study highlights the nuanced effects of processing conditions on MFG properties, emphasizing the retention of native characteristics in Vat-PT-treated human milk.
        Cover page: Investigating Milk Fat Globule Structure, Size, and Functionality after Thermal Processing and Homogenization of Human Milk.
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2018)
        Human milk is uniquely optimized for the needs of the developing infant. Its composition is complex and dynamic, driven primarily by maternal genetics, and to a lesser extent by diet and environment. One important component that is gaining attention is the milk fat globule (MFG). The MFG is composed of a triglyceride-rich core surrounded by a tri-layer membrane, also known as the milk fat globule membrane (MFGM) that originates from mammary gland epithelia. The MFGM is enriched with glycerophospholipids, sphingolipids, cholesterol, and proteins, some of which are glycosylated, and are known to exert numerous biological roles. Mounting evidence suggests that the structure of the MFG and bioactive components of the MFGM may benefit the infant by aiding in the structural and functional maturation of the gut through the provision of essential nutrients and/or regulating various cellular events during infant growth and immune education. Further, antimicrobial peptides and surface carbohydrate moieties surrounding the MFG might have a pivotal role in shaping gut microbial populations, which in turn may promote protection against immune and inflammatory diseases early in life. This review seeks to: (1) understand the components of the MFG, as well as maternal factors including genetic and lifestyle factors that influence its characteristics; (2) examine the potential role of this milk component on the intestinal immune system; and (3) delineate the mechanistic roles of the MFG in infant intestinal maturation and establishment of the microbiota in the alimentary canal.
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2018)
          Human milk is uniquely optimized for the needs of the developing infant. Its composition is complex and dynamic, driven primarily by maternal genetics, and to a lesser extent by diet and environment. One important component that is gaining attention is the milk fat globule (MFG). The MFG is composed of a triglyceride-rich core surrounded by a tri-layer membrane, also known as the milk fat globule membrane (MFGM) that originates from mammary gland epithelia. The MFGM is enriched with glycerophospholipids, sphingolipids, cholesterol, and proteins, some of which are glycosylated, and are known to exert numerous biological roles. Mounting evidence suggests that the structure of the MFG and bioactive components of the MFGM may benefit the infant by aiding in the structural and functional maturation of the gut through the provision of essential nutrients and/or regulating various cellular events during infant growth and immune education. Further, antimicrobial peptides and surface carbohydrate moieties surrounding the MFG might have a pivotal role in shaping gut microbial populations, which in turn may promote protection against immune and inflammatory diseases early in life. This review seeks to: (1) understand the components of the MFG, as well as maternal factors including genetic and lifestyle factors that influence its characteristics; (2) examine the potential role of this milk component on the intestinal immune system; and (3) delineate the mechanistic roles of the MFG in infant intestinal maturation and establishment of the microbiota in the alimentary canal.
            Cover page: Compositional Dynamics of the Milk Fat Globule and Its Role in Infant Development
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2021)
            Introduction: The functional role of milk for the developing neonate is an area of great interest, and a significant amount of research has been done. However, a lot of work remains to fully understand the complexities of milk, and the variations imposed through genetics. It has previously been shown that both secretor (Se) and Lewis blood type (Le) status impacts the human milk oligosaccharide (HMO) content of human milk. While some studies have compared the non-HMO milk metabolome of Se+ and Se- women, none have reported on the non-HMO milk metabolome of Se- and Le- mothers. Method and Results: To determine the differences in the non-HMO milk metabolome between Se-Le- mothers and other HMO phenotypes (Se+Le+, Se+Le-, and Se-Le+), 10 milk samples from 10 lactating mothers were analyzed using nuclear magnetic resonance (NMR) spectroscopy. Se or Le HMO phenotypes were assigned based on the presence and absence of 6 HMOs generated by the Se and Le genes. After classification, 58 milk metabolites were compared among the HMO phenotypes. Principal component analysis (PCA) identified clear separation between Se-Le- milk and the other milks. Fold change analysis demonstrated that the Se-Le- milk had major differences in free fatty acids, free amino acids, and metabolites related to energy metabolism. Conclusion: The results of this brief research report suggest that the milk metabolome of mothers with the Se-Le- phenotype differs in its non-HMO metabolite composition from mothers with other HMO phenotypes.
              Cover page: The Milk Metabolome of Non-secretor and Lewis Negative Mothers
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