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