The validation of biomarkers of metabolic efficacy in infant nutrition

婴儿营养代谢功效生物标志物的验证

• 批准号: BB/M027252/1
• 负责人: Albert Koulman
• 金额: $ 70.97万
• 依托单位: MRC Centre Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM027252%2F1
• 关键词: validation; biomarkers; metabolic; efficacy; infant

Breastfeeding is the best start for a baby's life. The World Health Organisation (WHO) recommends that all women should exclusively breastfeed their babies until six months of age. However not all women have the opportunity to exclusively breastfeed their babies. In the UK it is reported that whilst 81% of mothers start with breast feeding only 17% of infants are exclusively breast-fed until 3 months, and 1% until 6 months of age. This does not have to be the mother's choice, already in the first weeks 13% of the breast feeding mothers get advice to provide the baby with extra feeding. Thus there is a need to design breast-milk alternatives that mimic the nutritional quality of breast milk as closely as possible.Recent evidence suggests that non breast-fed infants have an increased risk of becoming obese and an increased risk of high blood pressure in later life. It is currently unclear why infant feeding practices have such a big impact on health outcomes later in life. However, breastfeeding seems to be metabolised differently by infants than formula milk; our research showed that babies that are breast fed have a significantly different blood lipid (fat) profile compared to bottle fed babies.The aim of this project is to develop novel methods to help us understand the mechanism(s) of the differences in the metabolism of bottle fed babies and breast fed babies. We want to identify specific lipids that can be used as markers that reflect the benefits of breastfeeding. We will do this by exploring changes in the lipid profiles of babies in the UK during their first year of life. By comparing blood markers with patterns of infant growth we will be able to identify markers that can be used to assess the metabolic response to breast-milk alternatives. We will also include mothers and infants from rural and urban sub-Saharan Africa to explore between population differences in the association between mode of feeding, blood lipid levels, and infant health outcomes'. One possible way in which mode of feeding may impact on the baby's metabolism is via bacteria in the gut (the gut microbiome). It is believed that, compounds in food, affect which bacteria live in the gut and that the different combinations of bacteria in the gut leads to different metabolic products that will be taken up into the blood stream. We do not know if these differences in the gut microbiome also affect the lipids in the blood. To explore this potential link, we will also study what the effect is of the gut microbiome of the babies on their metabolism. Recently we developed a method using high resolution mass spectrometry to determine a detailed lipid profile covering over a 100 lipids from one dried blood spot. This is a blood sample obtained from a heel prick and only requires a drop of blood spotted on paper. This is the most suitable method to study the metabolism of babies. We will adapt this dried blood spot based method to captures both lipids and metabolites dependent on gut microbiome. The identified markers, and the methods to measure these, will then be available for use by scientist and industry to study the effect of new formula or new feeding methods for infants who do not have the chance to be exclusively breast fed and give these babies the best possible start in life.

母乳喂养是婴儿生命最好的开始。世界卫生组织（WHO）建议所有女性应该完全母乳喂养婴儿，直到六个月大。然而，并非所有妇女都有机会完全母乳喂养婴儿。据报道，在英国，虽然81%的母亲开始母乳喂养，但只有17%的婴儿完全母乳喂养至3个月，1%至6个月。这并不一定是母亲的选择，已经有13%的母乳喂养母亲在最初几周内得到了为婴儿提供额外喂养的建议。因此，需要设计尽可能模仿母乳营养质量的母乳替代品。最近的证据表明，非母乳喂养的婴儿在以后的生活中患肥胖症和高血压的风险增加。目前还不清楚为什么婴儿喂养方法对以后的健康结果有如此大的影响。然而，母乳喂养的婴儿的代谢似乎与配方奶不同;我们的研究表明，母乳喂养的婴儿与母乳喂养的婴儿相比，血脂（脂肪）状况有显着不同。本项目的目的是开发新的方法来帮助我们了解母乳喂养婴儿和母乳喂养婴儿代谢差异的机制。我们希望确定可以用作反映母乳喂养益处的标志物的特定脂质。我们将通过探索英国婴儿在出生后第一年的血脂变化来做到这一点。通过比较血液标志物与婴儿生长模式，我们将能够确定可用于评估母乳替代品代谢反应的标志物。我们还将包括来自撒哈拉以南非洲农村和城市的母亲和婴儿，以探索喂养方式，血脂水平和婴儿健康结果之间的关联的人口差异。喂养模式可能影响婴儿新陈代谢的一种可能方式是通过肠道中的细菌（肠道微生物组）。据信，食物中的化合物会影响肠道中的细菌，肠道中细菌的不同组合会导致不同的代谢产物被吸收到血液中。我们不知道肠道微生物组的这些差异是否也会影响血液中的脂质。为了探索这种潜在的联系，我们还将研究婴儿肠道微生物组对他们新陈代谢的影响。最近，我们开发了一种方法，使用高分辨率质谱法，以确定详细的脂质分布，涵盖了100多个脂质从一个干血斑。这是一个从脚后跟穿刺获得的血液样本，只需要在纸上点一滴血。这是研究婴儿新陈代谢的最佳方法。我们将采用这种基于干血斑的方法来捕获依赖于肠道微生物组的脂质和代谢物。科学家和工业界将利用确定的标志物和测量这些标志物的方法，研究新配方奶粉或新喂养方法对没有机会完全母乳喂养的婴儿的影响，并为这些婴儿提供最好的生活开端。

项目成果

A co-ordinated transcriptional programme in the maternal liver supplies LC-PUFAs to the conceptus using phospholipids

• DOI: 10.1101/2023.06.23.546226
• 发表时间: 2023-06
• 期刊: bioRxiv
• 作者: Risha Amarsi;S. Furse;M. A. Cleaton;Sarah Maurel;Alice L Mitchell;A. Ferguson-Smith;N. Cenac;C. Williamson;A. Koulman;M. Charalambous

The translation of lipid profiles to nutritional biomarkers in the study of infant metabolism.

在婴儿代谢研究中，将脂质谱转换为营养生物标志物。

• DOI: 10.1007/s11306-017-1166-2
• 发表时间: 2017
• 期刊: Metabolomics : Official journal of the Metabolomic Society
• 作者: Acharjee A;Prentice P;Acerini C;Smith J;Hughes IA;Ong K;Griffin JL;Dunger D;Koulman A
• 通讯作者: Koulman A

Cysteine synthases CYSL-1 and CYSL-2 mediate C. elegans heritable adaptation to P. vranovensis infection

半胱氨酸合酶 CYSL-1 和 CYSL-2 介导线虫对弗兰诺文西斯感染的遗传适应

• DOI: 10.17863/cam.66701
• 发表时间: 2020
• 作者: Burton N

massPix: an R package for annotation and interpretation of mass spectrometry imaging data for lipidomics

MassPix：用于注释和解释脂质组学质谱成像数据的 R 包

• DOI: 10.17863/cam.13703
• 发表时间: 2017
• 作者: Bond N

SID-2 negatively regulates development likely independent of nutritional dsRNA uptake.

• DOI: 10.1080/15476286.2020.1827619
• 发表时间: 2021-06
• 期刊: RNA biology
• 影响因子: 4.1
• 作者: Braukmann F;Jordan D;Jenkins B;Koulman A;Miska EA
• 通讯作者: Miska EA