The influence of the milk microbiome on inflammation of the preterm infant

乳汁微生物组对早产儿炎症的影响

• 批准号: 9766395
• 负责人: Katherine Elizabeth Gregory
• 金额: $ 22.86万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-17 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9766395
• 关键词: 16S ribosomal RNA sequencing; Age; Antibiotics; Attenuated; Biological Markers; Birth; Blood; Blood specimen; Brain; Breastfed infant; Cells; Child; Childhood; Clinical; Communities; Complex; Consumption; Development; Dietary Intervention; Disease; Enteral; Foundations; Future; Genes; Gestational Age; Health; Hospitals; Human Microbiome; Human Milk; IL6 gene; IL8 gene; Immune; Immune response; Immune system; Immunoassay; Immunologic Factors; Immunologics; Immunology; Impairment; Infant; Inflammation; Inflammatory; Inflammatory Response; Inflammatory disease of the intestine; Intercellular adhesion molecule 1; Interleukin-1 beta; Interleukin-6; Intervention; Intestines; Knowledge; Learning; Life; Longevity; Measurable; Measures; Medicine; Metabolic Pathway; Methods; Milk; Morbidity - disease rate; Mothers; Necrotizing Enterocolitis; Neonatal Nursing; Nervous System Trauma; Neurodevelopmental Impairment; Neurologic; Newborn Infant; Nursing Research; Nutritional; Outcome; Pathogenesis; Positioning Attribute; Pregnancy; Premature Birth; Premature Infant; Proteins; Proteobacteria; Research Personnel; Risk; Risk Factors; Serum; Severity of illness; Source; Structure; Testing; Therapeutic; Time Study; Urine; associated symptom; base; clinical practice; cohort; cost; disability; economic implication; experience; genome sequencing; gut microbiome; immune health; immune system function; immunoregulation; improved functioning; infancy; infant morbidity; infant nutrition; intestinal fatty acid binding protein; microbial community; microbial host; microbiome; microbiome composition; milk microbiome; mortality; multidisciplinary; neonatal period; neonatal sepsis; novel; prevent; sex; statistics; urinary; whole genome

ABSTRACT/PROJECT SUMMARY Preterm birth is the leading cause of pediatric morbidity and mortality worldwide, with catastrophic health outcomes and significant economic implications. In spite of increasing survival, children born preterm continue to suffer suboptimal outcomes when compared to their full-term born counterparts. One of the common underpinnings associated with life-limiting health outcomes of the preterm infant is immature immune- regulation and an exaggerated inflammatory response. The preterm infant gut and brain are especially vulnerable to inflammation, as evidenced by multiple studies that have reproducibly shown that higher levels of inflammatory proteins measurable in the urine and blood as early as the first four weeks following birth are associated with both short and long-term intestinal and neurological health. Maternal breast milk (MBM) is known to be immuoprotective during infancy. However, little is known about the newly discovered milk microbiome following preterm birth, and the direct influence this may have on measures of intestinal or systemic inflammation. In this study, we will test our overall hypothesis that the taxa comprising the community structure of the milk microbiome influences measures of intestinal and systemic inflammation of the preterm infant during the early neonatal period. We will collect MBM, infant urine and blood samples from preterm mother-infant pairs at four study time points (1, 2, 4 weeks of age, and 36 weeks adjusted gestational age). 16s rRNA sequencing will define the community structure of the milk microbiome. Whole genome sequencing will identify species level taxa and bacterial functional potentials (genes and metabolic pathways) in infants who have the highest and lowest measures of inflammation assessed by levels of inflammatory proteins including urinary intestinal fatty acid binding protein (iFABP), and serum-based CRP, IL1β, IL6, IL8, ICAM-1. Defining the milk microbiome in the context of intestinal and systemic inflammation among preterm infants who are vulnerable to long-term impairment associated with immune regulated disease will build the scientific foundation for novel interventions that seek to therapeutically enrich enteral sources of infant nutrition. These interventions will have the potential to attenuate the inflammatory response of the preterm infant, thereby preventing disease and disability across the lifespan.

摘要/项目摘要 早产是全世界儿科发病和死亡的主要原因，给健康带来灾难性影响 成果和重大经济影响。尽管存活率不断提高，但早产儿仍继续 与足月出生的同龄人相比，他们会遭受次优的结果。常见的之一 与早产儿生命限制健康结果相关的基础是不成熟的免疫系统 调节和过度的炎症反应。早产儿的肠道和大脑尤其如此 易受炎症影响，多项研究重复表明，较高水平的 早在出生后的前四个星期就可以在尿液和血液中测量到炎症蛋白 与短期和长期的肠道和神经健康有关。母乳 (MBM) 是 已知在婴儿期具有免疫保护作用。然而，人们对新发现的牛奶知之甚少 早产后的微生物组，及其对肠道或肠道指标的直接影响 全身炎症。在这项研究中，我们将检验我们的总体假设，即组成群落的类群 乳汁微生物组的结构影响早产儿肠道和全身炎症的测量 新生儿早期的婴儿。我们将从早产儿收集肉骨粉、婴儿尿液和血液样本 四个研究时间点（1、2、4 周龄和 36 周调整胎龄）的母婴对。 16s rRNA 测序将定义乳汁微生物组的群落结构。全基因组测序 将识别婴儿的物种水平分类群和细菌功能潜力（基因和代谢途径） 通过炎症蛋白水平评估的炎症指标最高和最低的人 包括尿肠脂肪酸结合蛋白 (iFABP) 和血清 CRP、IL1β、IL6、IL8、ICAM-1。 在早产儿肠道和全身炎症的背景下定义乳汁微生物组 容易受到与免疫调节疾病相关的长期损害将建立科学的 为寻求治疗性丰富婴儿营养肠内来源的新颖干预措施奠定了基础。这些 干预措施将有可能减弱早产儿的炎症反应，从而 在整个生命周期预防疾病和残疾。

项目成果

Pregnancy-specific dietary guidelines for Americans are not met: Findings from a pilot study.

• DOI: 10.1002/rfc2.63
• 发表时间: 2023-12
• 期刊: Reproductive, female and child health
• 作者: El Habbal, Noura;Filatava, Evgenia J;Overton, Nicolette E;Gregas, Matt;Gregory, Katherine E
• 通讯作者: Gregory, Katherine E

Intestinal Inflammation is Significantly Associated With Length Faltering in Preterm Infants at Neonatal Intensive Care Unit Discharge.

• DOI: 10.1097/mpg.0000000000003455
• 发表时间: 2022-06-01
• 期刊: JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION
• 影响因子: 2.9
• 作者: Thai, Julie D.;Cherkerzian, Sara;Filatava, Evgenia J.;Luu, Ngan;Yamamoto, Hidemi S.;Fichorova, Raina N.;Belfort, Mandy B.;Gregory, Katherine E.
• 通讯作者: Gregory, Katherine E.

Human milk pH is associated with fortification, postpartum day, and maternal dietary intake in preterm mother-infant dyads.

• DOI: 10.1038/s41372-022-01492-5
• 发表时间: 2023-01
• 期刊: JOURNAL OF PERINATOLOGY
• 影响因子: 2.9
• 作者: Filatava, Evgenia Jen;Shelly, Colleen E.;Overton, Nicolette E.;Gregas, Matt;Glynn, Robert;Gregory, Katherine E.
• 通讯作者: Gregory, Katherine E.

The preterm human milk microbiota fluctuates by postpartum week and is characterized by gestational age and maternal BMI.

• DOI: 10.1128/mbio.02106-23
• 发表时间: 2023-12-19
• 期刊: MBIO
• 影响因子: 6.4
• 作者: Filatava, Evgenia Jen;Liu, Zhongmao;Xie, Jiaojiao;Tran, Dong-Binh;Chen, Kun;El Habbal, Noura;Weinstock, George;Zhou, Yanjiao;Gregory, Katherine E.
• 通讯作者: Gregory, Katherine E.