Prebiotic GOS and lactoferrin for beneficial gut microbiota with iron supplements

益生元 GOS 和乳铁蛋白通过铁补充剂有益肠道微生物群

• 批准号: 9753231
• 负责人: Gary M Brittenham
• 金额: $ 52.52万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9753231
• 关键词: 1 year old; 16S ribosomal RNA sequencing; Adverse effects; Affect; African; Anemia; Anti-Bacterial Agents; Area; Behavioral; Bifidobacterium; Cattle; Cause of Death; Cell model; Child; Childhood; Clinical; Clinical Trials; Colon; Development; Diarrhea; Double-Blind Method; Edetic Acid; Enteral; Enterobacteriaceae; Epithelial; Female of child bearing age; Fermentation; Ferrous fumarate; Formulation; Goals; Gram-Negative Bacteria; Growth; Home environment; Homeostasis; Immobilization; Immune; Immune system; Impaired cognition; In Vitro; Individual; Infant; Infection; Inflammation; Inflammatory; Inflammatory disease of the intestine; Intake; Intestines; Investigation; Iron; Iron deficiency anemia; Ivory Coast; Lactobacillus; Lactoferrin; Leukocyte L1 Antigen Complex; Malaria; Metabolic; Metabolism; Methods; Micronutrients; Modeling; Nutrient; Oligosaccharides; Oral; Pathogenicity; Peptides; Physical Performance; Pneumonia; Population; Powder dose form; Pregnant Women; Prevention; Production; Randomized; Randomized Clinical Trials; Research; Salmonella; School-Age Population; Shigella; Site; Small Intestines; Sodium; Systems Development; Virulence; Virulent; antimicrobial; co-infection; commensal microbes; design; dysbiosis; enteric pathogen; fecal microbiota; fortification; gastrointestinal infection; gut microbiome; gut microbiota; immunoregulation; improved; in vitro Model; in vivo; iron deficiency; iron supplement; iron supplementation; microbiome composition; microbiota; microbiota profiles; microorganism; mortality; nutrition; organic acid; pathogen; pathogenic Escherichia coli; prebiotics; prevent; treatment effect; virtual

Other Project Information: Project Summary/Abstract The ultimate goal of this research is to develop a means to safely administer iron supplements to infants in settings with a high infection burden. The hypothesis underlying this project is that promoting development of a beneficial, protective gut microbiota by co-administration of prebiotic galacto-oligosaccharides (GOS) and iron- sequestering bovine lactoferrin (bLF) during iron supplementation will prevent iron-induced increases of opportunistic enteropathogens that cause infection and inflammation. The proposed research will extend our established strategy of conjoining investigations in vivo with intestinal fermentation and cellular models in vitro. We will conduct a randomized clinical trial in 6 month-old Kenyan infants in conjunction with mechanistic microbiota studies using our established long-term continuous polyfermenter platform inoculated with immobilized fecal microbiota from Kenyan infants. The period from about 6 months to 1 year of age is vital both for iron nutrition and for the establishment of a healthy gut microbiome that promotes immune system development, local immune homeostasis and limits pathogen colonization. Oral iron supplements are associated with a significant 15% increase in the rate of diarrhea in children in malaria-endemic areas. Our most recent studies have shown that prebiotic galacto-oligosaccharides (GOS) can provide partial amelioration of the adverse effects of iron-induced dysbiosis by enhancing the growth of barrier populations of bifidobacteria and lactobacilli. We hypothesize that the combination of prebiotic GOS with bovine lactoferrin (bLF), adding iron sequestration, antimicrobial and immunomodulatory activities, will provide virtually complete protection against the adverse effects of added iron on the intestinal microbiota. Our research has two specific aims: (1) to conduct a randomized, controlled double-blind 9-month clinical trial in 6-month old Kenyan infants comparing the effects on gut microbiome composition among groups receiving in-home fortification for 6 months with micronutrient powders containing 5 mg iron (as sodium iron EDTA [2.5 mg] and ferrous fumarate [2.5 mg]) and (i) galacto-oligosaccharides (GOS; 7.5 g), (ii) bovine lactoferrin (bLF, 1.0 g), (iii) GOS (7.5 g) and bLF (1.0 g), and (iv) no GOS or bLF. Each infant will then be followed for an additional 3 months to determine the longer-term effects of the treatments. (2) to examine mechanisms of prebiotic GOS and iron-sequestering bLF on microbiota composition, enteropathogen development, microbiota functions and metabolic activity, and inflammatory potential in vitro with treatments paralleling those in Specific Aim 1, using immobilized fecal microbiota from Kenyan infants to inoculate our established long-term continuous polyfermenter intestinal model (PolyFermS) to mimic Kenyan infant colon conditions, together with cellular studies.

其他项目信息：项目摘要/摘要 这项研究的最终目标是开发一种为婴儿安全补充铁补充剂的方法。 感染负担高的环境。该项目的假设是促进 通过同时服用益生元低聚半乳糖 (GOS) 和铁，形成有益的、具有保护作用的肠道微生物群 在补铁过程中隔离牛乳铁蛋白 (bLF) 将防止铁诱导的乳铁蛋白增加 引起感染和炎症的机会性肠道病原体。拟议的研究将扩展我们的 建立了将体内研究与肠道发酵和体外细胞模型相结合的策略。 我们将对 6 个月大的肯尼亚婴儿进行一项随机临床试验，并结合机械学 使用我们已建立的长期连续聚合发酵平台进行微生物群研究，该平台接种了 来自肯尼亚婴儿的固定化粪便微生物群。大约6个月到1岁的这段时期对于孩子来说至关重要 用于铁营养和建立促进免疫系统的健康肠道微生物组 发育、局部免疫稳态并限制病原体定植。口服铁补充剂有 疟疾流行地区儿童腹泻率显着增加 15%。我们的 最近的研究表明，益生元低聚半乳糖 (GOS) 可以提供部分改善 通过促进双歧杆菌屏障种群的生长来研究铁引起的生态失调的不利影响 和乳酸杆菌。我们假设益生元 GOS 与牛乳铁蛋白 (bLF) 的组合，添加 铁螯合、抗菌和免疫调节活性，将提供几乎完整的保护 对抗添加铁对肠道微生物群的不利影响。我们的研究有两个具体目标： (1) 在6个月大的肯尼亚婴儿中进行一项随机、对照、双盲、为期9个月的临床试验 比较接受家庭强化的群体对肠道微生物组组成的影响 服用含有 5 毫克铁的微量营养素粉（如 EDTA 铁钠 [2.5 毫克] 和 富马酸亚铁 [2.5 毫克]）和 (i) 低聚半乳糖（GOS；7.5 克），(ii) 牛乳铁蛋白（bLF，1.0 g)，(iii) GOS (7.5 g) 和 bLF (1.0 g)，以及 (iv) 无 GOS 或 bLF。然后将跟踪每个婴儿 额外 3 个月的时间来确定治疗的长期效果。 (2) 研究益生元 GOS 和铁螯合 bLF 对微生物群组成的影响机制， 肠道病原体的发展、微生物群功能和代谢活动以及炎症潜力 体外处理与特定目标 1 中的处理平行，使用来自以下来源的固定化粪便微生物群： 肯尼亚婴儿接种我们建立的长期连续聚合发酵肠道模型 （PolyFermS）模拟肯尼亚婴儿结肠状况以及细胞研究。