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: 10388259
• 负责人: Gary M Brittenham
• 金额: $ 49.82万
• 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 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10388259
• 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; Female of child bearing age; Fermentation; Ferrous fumarate; Formulation; Goals; Gram-Negative Bacteria; Growth; Home; Homeostasis; Immobilization; Immune; Immune system; Impaired cognition; In Vitro; Individual; Infant; Infection; Inflammation; Inflammatory; 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 inflammation; gut microbiome; gut microbiota; immunoregulation; improved; in vitro Model; in vivo; infection burden; intestinal barrier; intestinal epithelium; 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 这项研究的最终目的是开发一种手段，以安全地管理铁补充剂 具有高感染负担的设置。该项目的基础假设是促进 有益的，保护性肠道菌群通过共同给药的益生元 - 摩酸 - 寡糖（GOS）和铁 - 补充铁期间隔离牛乳铁蛋白（BLF）将防止铁诱导的增加 机会性肠病原体会引起感染和炎症。拟议的研究将扩大我们的 建立的策略是在体外与肠发酵和细胞模型在体外结合研究的策略。 我们将在6个月大的肯尼亚婴儿中进行随机临床试验，并结合机械 使用我们已建立的长期连续多摄影仪平台进行的微生物群研究。 肯尼亚婴儿固定的粪便菌群。大约6个月到1岁的期间都至关重要 用于铁营养和建立健康的肠道微生物组，以促进免疫系统 发育，局部免疫稳态并限制了病原体定植。口服铁补充剂是 与疟疾流行病地区儿童腹泻率显着增加15％有关。我们的 最新的研究表明，益生元 - 摩洛糖 - 寡糖（GOS）可以提供部分改善 铁诱导的营养不良的不良影响，通过增强双歧杆菌的屏障群体的生长 和乳杆菌。我们假设益生元GO与牛乳铁蛋白（BLF）的结合，加上 铁隔离，抗菌和免疫调节活动将实际上提供完整的保护 与添加的铁对肠道菌群的不利影响。我们的研究有两个具体的目标： （1）在6个月大的肯尼亚婴儿中进行随机，受控的双盲9个月临床试验 比较接受纳入强化的组中对肠道微生物组组成的影响 用含5 mg铁的微量营养素粉末（作为钠铁EDTA [2.5 mg]和 亚铁富马酸盐[2.5 mg]）和（i）半乳糖 - 寡糖（GOS; 7.5 g），（ii）牛乳酸铁蛋白（BLF，1.0 g），（iii）GOS（7.5 g）和BLF（1.0 g），以及（iv）无GOS或BLF。然后，每个婴儿都会遵循 另外3个月来确定治疗的长期影响。 （2）检查益生物群组成的益生元GOS和铁序列BLF的机制， 肠病的发育，微生物群功能和代谢活性以及炎症潜力 使用固定的粪便微生物群，与与特定目标1中平行的治疗进行体外处理 肯尼亚婴儿接种我们已建立的长期连续多植物肠模型 （多率）与细胞研究一起模仿肯尼亚婴儿结肠条件。

项目成果

Short-term periods of strenuous physical activity lower iron absorption.

短期的剧烈体力活动会降低铁的吸收。

• DOI: 10.1093/ajcn/nqaa365
• 发表时间: 2021
• 期刊: The American journal of clinical nutrition
• 作者: Brittenham,GaryM

Long-term continuous cultivation of Kenyan infant fecal microbiota using the host adapted PolyFermS model.

使用宿主适应的 PolyFermS 模型长期连续培养肯尼亚婴儿粪便微生物群。

• DOI: 10.21203/rs.3.rs-3101157/v1
• 发表时间: 2023
• 期刊: Research square
• 作者: Rachmühl,Carole;Lacroix,Christophe;Cabrera,PaulaMomo;Geirnaert,Annelies
• 通讯作者: Geirnaert,Annelies

Validation of a batch cultivation protocol for fecal microbiota of Kenyan infants.

• DOI: 10.1186/s12866-023-02915-9
• 发表时间: 2023-07-04
• 期刊: BMC MICROBIOLOGY
• 影响因子: 4.2
• 作者: Rachmuhl, Carole;Lacroix, Christophe;Giorgetti, Ambra;Stoffel, Nicole U. U.;Zimmermann, Michael B. B.;Brittenham, Gary M. M.;Geirnaert, Annelies
• 通讯作者: Geirnaert, Annelies