Johnson Kelsey E, Heisel Timothy, Allert Mattea, Fürst Annalee, Yerabandi Nikhila, Knights Dan, Jacobs Katherine M, Lock Eric F, Bode Lars, Fields David A, Rudolph Michael C, Gale Cheryl A, Albert Frank W, Demerath Ellen W, Blekhman Ran
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, USA.
Division of Neonatology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA.
bioRxiv. 2023 Jan 25:2023.01.24.525211. doi: 10.1101/2023.01.24.525211.
Human milk is a complex mix of nutritional and bioactive components that provide complete nutrition for the infant. However, we lack a systematic knowledge of the factors shaping milk composition and how milk variation influences infant health. Here, we used multi-omic profiling to characterize interactions between maternal genetics, milk gene expression, milk composition, and the infant fecal microbiome in 242 exclusively breastfeeding mother-infant pairs. We identified 487 genetic loci associated with milk gene expression unique to the lactating mammary gland, including loci that impacted breast cancer risk and human milk oligosaccharide concentration. Integrative analyses uncovered connections between milk gene expression and infant gut microbiome, including an association between the expression of inflammation-related genes with IL-6 concentration in milk and the abundance of in the infant gut. Our results show how an improved understanding of the genetics and genomics of human milk connects lactation biology with maternal and infant health.
母乳是营养成分和生物活性成分的复杂混合物，能为婴儿提供全面营养。然而，我们缺乏对塑造乳汁成分的因素以及乳汁变化如何影响婴儿健康的系统认识。在此，我们采用多组学分析方法，对242对纯母乳喂养的母婴对中母亲遗传学、乳汁基因表达、乳汁成分和婴儿粪便微生物群之间的相互作用进行了表征。我们鉴定出487个与泌乳乳腺特有的乳汁基因表达相关的基因位点，包括影响乳腺癌风险和人乳寡糖浓度的位点。综合分析揭示了乳汁基因表达与婴儿肠道微生物群之间的联系，包括炎症相关基因的表达与乳汁中白细胞介素-6浓度以及婴儿肠道中某种物质丰度之间的关联。我们的研究结果表明，对母乳遗传学和基因组学的深入理解如何将泌乳生物学与母婴健康联系起来。
