The relationship of fecal microbiomes and nutritional status in CF

CF患者粪便微生物群与营养状况的关系

• 批准号: 9134726
• 负责人: Lucas R Hoffman
• 金额: $ 65.35万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-22 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9134726
• 关键词: Address; Ancillary Study; Animal Model; Animals; Antibiotic Therapy; Antibiotics; Bacteria; Bacterial Genes; Bacteroides; Bioinformatics; Body mass index; Breast Feeding; Carbohydrates; Caring; Characteristics; Child; Chronic Disease; Clinical; Clinical Data; Clinical Research; Clinical Trials; Complement; Complex; Computing Methodologies; Cystic Fibrosis; DNA Sequence; Data; Dietary Intervention; Dietary intake; Disease; Early Diagnosis; Early Intervention; Early treatment; Enrollment; Escherichia coli; Evolution; Exocrine pancreatic insufficiency; Failure; Fat-Soluble Vitamin; Fatty Acids; Fatty acid glycerol esters; Feces; Foundations; Functional disorder; Funding; Future; Gastrointestinal Diseases; Gastrointestinal tract structure; Genes; Goals; Growth; Harvest; Health; Height; Hereditary Disease; Human; Immune system; Infant; Inflammation; Inflammatory disease of the intestine; Intake; Intervention; Intestinal Diseases; Intestinal Obstruction; Intestines; Lead; Leukocyte L1 Antigen Complex; Life; Life Expectancy; Link; Lipids; Longevity; Lung; Lung diseases; Machine Learning; Malabsorption Syndromes; Malnutrition; Massive Parallel Sequencing; Measures; Metabolic; Metagenomics; Methods; Microbe; Micronutrients; Minerals; Morbidity - disease rate; Multicenter Studies; Neonatal Screening; Nutrient; Nutritional; Nutritional Study; Nutritional status; Observational Study; Obstruction; Outcome; Pancreatic enzyme; Parents; Pathway interactions; Pharmaceutical Preparations; Phylogenetic Analysis; Play; Process; Proteins; Proteobacteria; Research; Resources; Rest; Role; Sampling; Serum; Severities; Specimen; Study models; Systems Biology; Techniques; Testing; United States National Institutes of Health; Visit; Vitamins; Volatile Fatty Acids; Weight; absorption; analytical method; aqueous; candidate marker; children with cystic fibrosis; design; dosage; early cystic fibrosis; enzyme replacement therapy; experience; gastrointestinal; gastrointestinal sign; gastrointestinal symptom; gut microbiome; gut microbiota; improved; infancy; infant nutrition; meetings; metabolomics; metagenome; microbial; microbiome; microbiota; mortality; next generation; novel; nutrient absorption; nutrient metabolism; nutrition; routine care; uptake

 DESCRIPTION (provided by applicant): Intestinal tract disease is responsible for a substantial amount of the morbidity and mortality among people with the genetic disease cystic fibrosis (CF). The manifestations of CF intestinal disease frequently occur during infancy and result from pancreatic exocrine insufficiency (PI), resulting in profound nutrient malabsorption and malnutrition, and consequently in growth failure and intestinal obstruction. Despite aggressive, early nutritional intervention with pancreatic enzyme replacement and other therapies, early growth failure remains common among infants with CF, suggesting that characteristics other than PI contribute to growth and nutritional failure in infants with CF. The identification of thes growth and nutritional determinants in children with CF therefore remains a key research goal in CF care. Recently, a clue to a potentially critical contributor to nutrient and energy uptake in children has emerged from the study of the microbes present in the gastrointestinal tract- the gut microbiota. Research has identified a complex relationship between gut microbiota, nutritional intake, nutrient absorption, and other health measures. GI tract microbes are known to contribute significantly to human nutrient metabolism and energy harvest, and they are altered in many disease states. Therefore, infant GI tract microbes may represent important determinants of CF nutritional outcomes, which in turn can significantly impact severity of lung disease and overall longevity. We recently showed that infants and children with CF had GI microbiota that differ markedly from those of children without CF, and that this dysbiosis correlated with severity of GI dysfunction. However, the relationships between CF GI microbiota with growth and other clinically important outcomes have not been studied. We hypothesize that the intestinal microbiomes among children with CF correlate with severity of malabsorption, intestinal inflammation, gastrointestinal signs and symptoms, vitamin and mineral deficiency, and nutritional status. To test these hypotheses, this ancillary study will define the fecal microbiomes of 250 infants with CF being enrolled in an ongoing multicenter study of infant nutrition (the Baby Observational NUtrition Study (BONUS), funded by the Cystic Fibrosis Foundation and the National Institutes of Health) using ultra high-throughput, culture-independent sequencing methods. With these resources, we will (1) define the fecal microbiomes, composed of the microbiota (the species of microbes present) and metagenomes (the microbial genes present, which reflects the metabolic capacity of the microbiota) of at least four stool samples per subject over the first year of life, and (2) determine the relationship of fecal microbiomes, and their evolution over the year of study, with nutritional and clinical parameters (including weight, height, body mass index, growth rate of each of these parameters among subjects, serum vitamin levels, fecal nutrient and metabolite content, GI symptoms, and measures of inflammation). We will use massively parallel next- generation DNA sequencing methods, combined with advanced bioinformatic analytical methods, with which we have extensive experience. Our goal is to define the role of the infant CF GI microbiome in growth and nutrition, with the hope of identifying interventions that will improve early growth, and thus long-term outcomes, in CF.