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: 9349480
• 负责人: Lucas R Hoffman
• 金额: $ 61.97万
• 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/9349480
• 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; Complex; Computing Methodologies; Cystic Fibrosis; DNA analysis; DNA sequencing; Data; Dietary Intervention; Dietary intake; Disease; Early Diagnosis; Early Intervention; 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; 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; Microbiology; 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; 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; gene complementation; gut microbiome; gut microbiota; improved; infancy; infant nutrition; metabolomics; metagenome; microbial; microbiome; microbiota; mortality; next generation; novel; nutrient absorption; nutrient metabolism; nutrition; public health relevance; 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.

 描述（由适用提供）：肠道疾病负责遗传疾病囊性纤维化（CF）的患者的次要数量发病率和死亡率。 CF肠道疾病的表现经常在婴儿期发生，并由胰腺外分泌功能不全（PI）引起，导致了深远的营养不良和营养不良，因此导致生长衰竭和肠道反应。尽管对胰酶替代和其他疗法进行了积极的早期营养干预，但患有CF的婴儿的早期生长失败仍然很普遍，这表明PI以外的特征有助于CF婴儿的生长和营养衰竭。因此，CF儿童的生长和营养决定者的鉴定仍然是CF护理的关键研究目标。最近，从胃肠道中存在的微生物的研究中出现了对儿童营养和能量吸收的潜在至关重要的贡献的线索。研究已经确定了肠道菌群，营养摄入量，营养吸收和其他健康措施之间的复杂关系。已知胃肠道微生物对人类的营养代谢和能量收获有显着贡献，并且在许多疾病状态下它们都会改变。因此，婴儿胃肠道微生物可能代表CF营养结果的重要决定剂，进而可以显着影响肺部疾病的严重程度和整体寿命。我们最近表明，儿童和患有CF的儿童的胃肠道菌群与没有CF儿童的儿童明显不同，并且这种营养不良与GI功能障碍的严重程度相关。但是，CF GI微生物群与生长与其他临床重要结果之间的关系尚未研究。我们假设CF儿童的肠道微生物组与吸收不良，肠道感染，胃肠道体征和症状，维生素和矿物质缺乏以及营养状况相关。 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.借助这些资源，我们将（1）定义由微生物群（存在的微生物物种）和宏基因（存在的微生物基因（反映微生物基因）组成的粪便微生物组，这反映了至少四个受试者的生命中的小粪便的代谢能力），并在生命的第一年和（2）确定了fec and vecal microbi的关系，并确定效果关系的关系，以及他们的vecal vers of Fecal的关系，以及他们的ver of fie and ves of fie and ves of Fecal的关系。临床参数（包括体重，身高，体重指数，受试者之间每个参数的生长速率，血清维生素水平，粪便养分和代谢物含量，GI症状以及炎症的测量值）。我们将使用大量平行的下一代DNA测序方法，结合高级生物信息学分析方法，我们拥有丰富的经验。我们的目标是确定婴儿CF GI微生物组在生长和营养中的作用，希望确定可以改善早期生长的干预措施，从而在CF中的长期结局。