Exploring Associations between Human Milk Oligosaccharides and Atherosclerosis Risk Factors in Infancy and Early Childhood

探索母乳低聚糖与婴儿期和幼儿期动脉粥样硬化危险因素之间的关联

基本信息

批准号：
10491367
负责人：
Lars Bode
金额：
$ 17.17万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-20 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10491367
关键词：
4 year old Accounting Acute Address Affect American Heart Association Asthma Atherosclerosis Biomedical Engineering Birth Blood Circulation Body Composition Breast Feeding Breastfed infant C-reactive protein Carbohydrates Cardiovascular Diseases Cardiovascular system Cause of Death Cessation of life Child Childhood Cholesterol Chronic Clinical Cognition Cohort Studies Colon Communicable Diseases Complex Consensus Data Development Disease Disease Outcome Disease model Early Intervention Elderly Growth Health Care Costs Human Human Milk Hypersensitivity Immune Infant Infant Development Infant Health Inflammation Inflammatory Innate Immune Response Intervention Knowledge Lactation Lactose Life Ligands Linear Regressions Link Lipids Mammals Measures Metabolic Metadata Microbe Milk Modeling Mothers Mus Myocardial Infarction Oligosaccharides Outcome Phenotype Plasma Principal Component Analysis Resources Risk Risk Factors Risk Marker Sampling Shapes Small Intestines Solid Stroke Structure Technology Testing Time Toll-like receptors Translating Translations Triglycerides Woman atherosclerosis risk base biobank cardiometabolism cardiovascular disorder prevention cardiovascular disorder risk disorder risk early childhood economic cost emerging adult epidemiologic data gut microbiome infancy infant gut microbiome inflammatory marker inter-individual variation lipid metabolism lipidomics metabolomics microbiome mortality mouse model neurodevelopment pre-clinical prebiotics prevent

项目摘要

ABSTRACT Cardiovascular disease (CVD) is the leading cause of mortality, accounting for over a third of all deaths globally. CVD is caused by atherosclerosis, a complex chronic inflammatory disorder that results from chronic damage to the arterial wall by inflammation and lipid accumulation. Atherosclerosis begins in early life and is essentially universal by early adulthood. Thus, there is broad consensus that CVD prevention should begin early when adverse trajectories may be most modifiable – potentially as early as during infancy. Epidemiological data show that breastfed infants are at lower risk of developing CVD later in life, however, the protective components in human breastmilk and underlying mechanisms that contribute to the beneficial effects of breastfeeding remain unknown. After lactose and lipids, human milk oligosaccharides (HMOs), a group of complex carbohydrates, are the third most abundant component of human breastmilk. HMOs – either directly, or indirectly through shaping the infant gut microbiome – can impact infant inflammation and lipid metabolism, the two key contributors to atherosclerosis and CVD. In fact, our preliminary data shows that mice that received the HMO 3’-sialyllactose (3’SL) with the dam’s milk during the breastfeeding period had significantly lower plasma triglyceride and cholesterol levels and developed less atherosclerosis later in life. Here, we aim to explore whether these observed beneficial effects translate from mice to humans. Based on the finding that HMO composition varies between women and has been associated with several infant health and disease outcomes, we propose to test the hypothesis that HMO amount and composition associate with early preclinical markers of CVD and metabolic risk, and markers of inflammation from birth to early childhood. We will leverage the extraordinary resources of the Barwon Infant Study (BIS), one of the most comprehensive pre-birth cohort studies of cardiometabolic and inflammatory phenotypes in the world, apply state-of-the-art technology to measure HMO composition in biobanked breastmilk and infant plasma samples, and test whether HMO concentrations associate with infant lipidomic, metabolic, and cardiovascular phenotypes (AIM 1) as well as infant markers of inflammation (AIM 2). Knowledge gained from the successful completion of the proposed project will add to the existing preclinical data that established causal relationships. Together, the results will greatly enhance our understanding why breastfed infants are at lower risk of later CVD and form the basis for early life interventions. This is particularly timely as HMOs like 3’SL are now synthesized in bioengineered microbes and stand ready as new, inexpensive, scalable and safe options to help prevent CVD early in life when adverse trajectories may be most modifiable and help address the substantial and increasing health and economic costs of CVD.

抽象的心血管疾病（CVD）是导致死亡的主要原因，占全球死亡总数的三分之一以上。 CVD 是由动脉粥样硬化引起的，动脉粥样硬化是一种复杂的慢性炎症性疾病，由慢性损伤引起动脉壁因炎症和脂质积聚而发生，并且本质上是在生命早期开始的。因此，人们普遍认为，CVD 预防应尽早开始。流行病学数据显示，不良轨迹可能是最容易改变的——可能早在婴儿期就发生了。母乳喂养的婴儿在以后的生活中患心血管疾病的风险较低，但是，母乳喂养的婴儿中的保护成分人类母乳和有助于母乳喂养有益效果的潜在机制仍然存在继乳糖和脂质之后，母乳低聚糖（HMO）是一组复杂的碳水化合物，是人类母乳中第三丰富的成分——无论是直接的还是间接的。塑造婴儿肠道微生物群——可以影响婴儿炎症和脂质代谢，这是两个关键因素事实上，我们的初步数据显示，接受 HMO 3'-唾液酸乳糖的小鼠。 (3’SL) 与母乳喂养期间的母乳相比，血浆甘油三酯显着降低，并且在这里，我们的目的是探讨这些是否会降低胆固醇水平并在以后的生活中减少动脉粥样硬化。观察到的有益效果从小鼠转移到人类基于 HMO 成分变化的发现。女性之间并且与一些婴儿健康和疾病结果相关，我们建议测试 HMO 含量和成分与 CVD 和代谢的早期临床前标志物相关的假设从出生到幼儿期的风险和炎症标志物，我们将利用非凡的资源。 Barwon 婴儿研究 (BIS)，最全面的心脏代谢和出生前队列研究之一世界各地的炎症表型，应用最先进的技术来测量 HMO 成分生物库中的母乳和婴儿血浆样本，并测试 HMO 浓度是否与婴儿相关脂质组学、代谢和心血管表型 (AIM 1) 以及婴儿炎症标志物 (AIM 2)。从成功完成拟议项目中获得的知识将添加到现有的临床前数据中建立因果关系的结果将极大地增强我们对母乳喂养原因的理解。婴儿以后患 CVD 的风险较低，并构成早期生命干预的基础，因为这一点特别及时。像 3'SL 这样的 HMO 现在是在生物工程微生物中合成的，并且是一种新型、廉价、可扩展的 HMO 以及有助于在生命早期预防 CVD 的安全选择，此时不利的轨迹可能是最容易改变的并有帮助解决 CVD 带来的巨大且不断增加的健康和经济成本。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Age-dependent associations of human milk oligosaccharides with body size and composition up to 4 years of age.

母乳低聚糖与 4 岁以下体型和成分的年龄相关性。

DOI：
发表时间：
2023-05
期刊：
影响因子：
0
作者：
Mansell, Toby;Furst, Annalee;O'Hely, Martin;Chang, Melinda;Ponsonby, Anne;Vuillermin, Peter;Tang, Mimi Lk;Burgner, David;Saffery, Richard;Bode, Lars;Barwon Infant Study Investigator Group
通讯作者：
Barwon Infant Study Investigator Group