Prebiotic GOS and lactoferrin for beneficial gut microbiota with iron supplements

其他项目信息：项目概要/摘要 这项研究的最终目标是开发一种方法，安全地管理铁补充剂的婴儿， 高感染负担的环境。这个项目的假设是，促进一个 有益的，保护肠道微生物群通过共同给予益生元低聚半乳糖（GOS）和铁， 在补铁过程中螯合牛乳铁蛋白（bLF）将防止铁诱导的 导致感染和炎症的机会性肠道病原体。这项研究将扩大我们的 建立了将体内研究与体外肠发酵和细胞模型相结合的策略。 我们将在6个月大的肯尼亚婴儿中进行一项随机临床试验， 微生物群研究使用我们建立的长期连续聚合发酵罐平台接种 来自肯尼亚婴儿的固定粪便微生物。大约6个月到1岁的时期是至关重要的， 铁营养和建立健康的肠道微生物组，促进免疫系统 发育，局部免疫稳态和限制病原体定植。口服铁补充剂 与疟疾流行地区儿童腹泻率显著增加15%有关。我们 最近的研究表明，益生元低聚半乳糖（GOS）可以部分改善 铁诱导的生态失调的不利影响，通过提高生物屏障细菌种群的增长， 和乳酸杆菌。我们假设益生元GOS与牛乳铁蛋白（bLF）的组合， 铁螯合、抗微生物和免疫调节活性将提供几乎完全的保护 对抗添加的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为期9个月的随机对照双盲临床试验 比较接受家庭强化的人群对肠道微生物组组成的影响 用含有5毫克铁的微量营养素粉末（以EDTA铁钠[2.5毫克]和 富马酸亚铁[2.5 mg]）和（i）低聚半乳糖（GOS; 7.5 g），（ii）牛乳铁蛋白（bLF，1.0 g），（iii）GOS（7.5g）和bLF（1.0g），和（iv）无GOS或bLF。每一个婴儿都将被跟踪一个 另外3个月，以确定治疗的长期效果。 (2)为了检查益生元GOS和铁螯合bLF对微生物群组成的机制， 肠道病原体发育、微生物群功能和代谢活性以及炎症潜力 在体外，使用与特定目标1中的处理平行的处理，使用来自 肯尼亚婴儿建立长期连续的多发酵肠模型 （PolyFermS）以模拟肯尼亚婴儿结肠状况，连同细胞研究。

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.