Prebiotic GOS and lactoferrin for beneficial gut microbiota with iron supplements

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安全地给婴儿服用补铁的方法。 感染负担高的环境。这个项目背后的假设是，促进一种 益生素低聚半乳糖(GOS)和铁联合给药有利于肠道微生物区系的保护 在补铁过程中隔离牛乳铁蛋白(BLF)将防止铁诱导的 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 建立了体内研究、肠道发酵和体外细胞模型相结合的策略。 我们将在6个月大的肯尼亚婴儿身上进行一项随机临床试验，并联合机械师 使用我们建立的长期连续聚合发酵罐平台进行微生物区系研究 来自肯尼亚婴儿的固定化粪便微生物群。从大约6个月到1岁的时期是至关重要的 用于铁营养和建立健康的肠道微生物群，促进免疫系统 发展、局部免疫动态平衡和限制病原体定植。口服铁质补充剂 与疟疾流行地区儿童腹泻率显著增加15%有关。我们的 最近的研究表明，益生素半乳低聚糖(GOS)可以提供部分改善 铁诱导的生物失调通过促进双歧杆菌屏障种群的生长而产生的不利影响 还有乳酸菌。我们假设益生菌GOS与牛乳铁蛋白(BLF)的结合，添加了 铁的隔离、抗微生物和免疫调节活性，将提供几乎完全的保护。 防止添加铁对肠道微生物区系的不利影响。我们的研究有两个具体目标： (1)对6个月大的肯尼亚婴儿进行随机对照双盲9个月的临床试验 居家防御工事对肠道微生物群组成影响的比较 用含有5毫克铁的微量营养素粉末(如EDTA铁钠[2.5毫克]和 富马酸亚铁[2.5毫克])和(I)半乳低聚糖(GOS；7.5g)，(Ii)牛乳铁蛋白(BLF，1.0 G)，(Iii)GOS(7.5g)和BLF(1.0g)，以及(Iv)没有GOS或BLF。然后，每个婴儿将被跟踪一次 另外3个月，以确定治疗的长期效果。 (2)研究益生菌GOS和固铁BLF对微生物区系组成的影响机制。 肠道病原体的发展、微生物区系功能和代谢活性以及炎症潜能 在体外，使用固定的粪便微生物群进行与特定目标1平行的处理 肯尼亚婴儿接种我们建立的长期持续多发酵器肠模型 (PolyFermS)模拟肯尼亚婴儿的结肠条件，并进行细胞研究。

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.