Date of Award

Summer 8-2022

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Food Science

First Advisor

John Miklavcic

Second Advisor

Laura Glynn

Third Advisor

Jennifer Hahn-Holbrook

Abstract

As human milk supports growth and development, the World Health Organization and the American Academy of Pediatrics advise exclusive consumption of human milk for the first six months of life. Human milk contains numerous bioactive components, including extracellular vesicles (EVs). Single nucleotide polymorphisms (SNPs) in the FADS gene cluster that encodes the enzymes FADS1 and FADS2 may impact the concentrations of long-chain polyunsaturated fatty acids (LCPUFA) in human milk EVs. As integral components of the lipid membrane, the specific composition or balance of LCPUFAs may impact the bioavailability of EVs in newborns consuming human milk. The objective of this study was to determine the relation between genetic variation in FADS1 & FADS2 with the LCPUFA content of EVs from human milk. The hypothesis was that a mother with SNPs in FADS1 and/or FADS2 that encoded for lower functioning δ-5 and/or δ-6 desaturase enzymes would have lower amounts of LCPUFAs in EVs from human milk and vice vera. Maternal demographic data, human milk (n=70), and saliva samples (n=80) were collected from mothers who were under the care of health clinics in Orange County, California (USA) between 2015-2017 at 2-weeks of lactation. High sensitivity quantitative lipidomic analysis of fatty acids in human milk was completed by gas chromatography-mass spectrometry. Saliva samples were analyzed with pyrosequencing for SNPs rs174546 (FADS1) and rs174575 (FADS2) genotyping. The fatty acid content of EVs from human milk (n=35) was analyzed using gas chromatography-mass spectrometry high sensitivity quantitative lipidomic analysis. All statistical analysis was completed in R 4.1.2. Results showed vii that rs174546 genotype is an independent predictor of the arachidonic acid (AA) content (%w/w) in EVs from human milk (p-value 0.0087). It was also observed that individuals with rs174575 CC genotype have a statistically significantly greater average relative percent of eicosapentaenoic acid in EVs compared to rs174575 G carriers (p-value 0.0044). Lower content of LCPUFAs in EVs from human milk may be due to lower fatty acid desaturase activity in mothers who are carriers rs174546 A allele and/or rs174575 G allele. Whether the altered lipid composition of EVs alters EV bioavailability or downstream functions requires further investigation.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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