Dietary and microbial predictors of childhood obesity risk

儿童肥胖风险的饮食和微生物预测因素

• 批准号: 9892995
• 负责人: Robert Stephen Chapkin
• 金额: $ 43.63万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892995
• 关键词: Age; Birth; Body Composition; Body Weight; Body fat; Breastfed infant; Child; Child Health; Data; Diet; Dietary Intervention; Dietary intake; Environmental Risk Factor; Epithelial Cells; FFAR2 gene; FFAR3 gene; Feces; Fingers; Food; Gene Expression; Gene Expression Profiling; Genes; Goals; Growth; Growth and Development function; Health; Human; Human Milk; Immune; Infant; Infant formula; Life; Link; Mediating; Metabolic; Methodology; Mission; Modeling; Molecular; Mothers; Nonesterified Fatty Acids; Nutritional; Obesity; Oligosaccharides; Outcome; Pathway interactions; Patients; Positioning Attribute; Postpartum Period; Prevention; Recombinant DNA; Regulation; Research; Risk; Signal Transduction; Solid; Systems Biology; Testing; Thinness; Time; United States National Institutes of Health; Volatile Fatty Acids; Weaning; Weight; Weight Gain; analytical method; cohort; differential expression; early-life nutrition; experimental study; fecal microbiome; fecal microbiota; gut microbiota; host-microbe interactions; improved; innovation; insight; intestinal epithelium; metatranscriptome; metatranscriptomics; microbial; microbial community; microbial host; microbiome; microbiota; molecular marker; novel; nutrition; obesity in children; obesity risk; prebiotics; precision medicine; prospective; receptor; transcriptome

Project Summary/Abstract: The first three years-of-life are critically important for establishing growth trajectories and gut microbiota composition, both of which are influenced by diet and other environmental factors. Obesity rates are increasing worldwide and infants who are formula-fed (FF) for the first 6 months of life are ~2.5-times more likely to be obese at 2-years than breast-fed infants (BF); however, little data exists on infants who are both BF and FF (CF). Gut microbial composition is a determinant of obesity risk and microbiota differences exist between BF- vs. FF-fed infants, but less is known about the microbiota of CF infants. Human milk oligosaccharides (HMO) and prebiotics are fermented to short chain fatty acids (SCFA), which signal to the host through the free fatty acid receptors FFAR2 and FFAR3 to influence immune and metabolic function and obesity risk. We have shown that the microbiota and SCFA composition differ between FF and BF infants and that systems biology approaches that combine SCFA and FFAR-linked genes expression in exfoliated intestinal epithelial cells discriminate BF from FF infants. However, it is unknown whether these factors directly influence infant weight gain. The goal of this proposal is to determine how differences in dietary prebiotics influence mutualistic host-microbe interactions in a longitudinal, prospective birth cohort of 440 children and to relate those to infant growth trajectory and weight and body composition at age 3. Our central hypothesis is that dietary HMO and prebiotics produce different microbiome and SCFA composition in HM, FF and CF infants and that SCFA will mediate infant growth trajectories and body composition through interactions with gut FFAR. The proposed experiments will use systems biology approaches to illuminate transgenomic cross- talk between host exfoliated intestinal epithelial cells and the gut microbiota will provide mechanistic insight into the molecular pathways underlying host-microbe interactions in the gut that are associated with infant weight gain and body composition. Two specific aims will be undertaken to test our central hypothesis: 1) Determine the impact of early nutrition on microbiota composition and short chain fatty acid composition and relate those findings to growth trajectories in the first 3 years-of-life and BMI and body composition at age 3.; and 2) Annotate host exfoliated epithelial cell transcriptome and bacterial metatranscriptome profiles and elucidate host/commensal relationships focusing on FFAR-linked pathways and relate those findings to growth trajectories in the first 3 years-of-life and BMI and body composition at age 3. Our team is ideally positioned to undertake this research. Our pioneering noninvasive approach that simultaneously monitors gene expression in exfoliated epithelial cells and gut microbiota of infants is highly innovative. This body of work is significant because molecular biomarkers that define the relationship between dietary intake, microbiota composition, host gene expression and child health outcomes will be identified. These host-microbial molecular finger prints will enable patient-powered precision medicine to optimize infant growth and reduce childhood obesity risk.

项目摘要/摘要：生命的前三年对于建立成长至关重要 轨迹和肠道微生物群组成，两者都受到饮食和其他环境的影响 因素。全球肥胖率不断上升，出生后前 6 个月采用配方奶喂养 (FF) 的婴儿 2 岁时肥胖的可能性是母乳喂养婴儿 (BF) 的约 2.5 倍；然而，关于 既是 BF 又是 FF (CF) 的婴儿。肠道微生物组成是肥胖风险和微生物群的决定因素 BF 喂养与 FF 喂养的婴儿之间存在差异，但人们对 CF 婴儿的微生物群知之甚少。人类 乳寡糖 (HMO) 和益生元发酵为短链脂肪酸 (SCFA)，这会发出信号 宿主通过游离脂肪酸受体FFAR2和FFAR3影响免疫和代谢功能 和肥胖风险。我们已经证明 FF 和 BF 婴儿的微生物群和 SCFA 组成不同 系统生物学方法结合了 SCFA 和 FFAR 相关基因在脱落细胞中的表达 肠上皮细胞区分 BF 和 FF 婴儿。但尚不清楚这些因素是否直接影响 影响婴儿体重增加。该提案的目标是确定膳食益生元的差异如何 影响 440 名儿童的纵向前瞻性出生队列中的宿主-微生物互利相互作用，并 将这些与婴儿生长轨迹以及 3 岁时的体重和身体成分联系起来。我们的中心假设是 膳食 HMO 和益生元在 HM、FF 和 CF 中产生不同的微生物组和 SCFA 组成 SCFA 将通过与婴儿的相互作用来调节婴儿的生长轨迹和身体成分 肠道 FFAR。拟议的实验将使用系统生物学方法来阐明转基因组交叉 宿主脱落的肠上皮细胞和肠道微生物群之间的对话将提供机制上的见解 肠道中与婴儿体重相关的宿主-微生物相互作用的分子途径 增益和身体成分。将采取两个具体目标来检验我们的中心假设：1）确定 早期营养对微生物群组成和短链脂肪酸组成的影响并将其联系起来 生命最初 3 年的生长轨迹以及 3 岁时的 BMI 和身体成分的研究结果；和 2) 注释宿主脱落上皮细胞转录组和细菌宏转录组谱并阐明 宿主/共生关系侧重于 FFAR 相关途径，并将这些发现与生长联系起来 生命最初 3 年的轨迹以及 3 岁时的 BMI 和身体成分。我们的团队非常适合 开展这项研究。我们开创性的非侵入性方法可同时监测基因表达 在脱落的上皮细胞和婴儿的肠道微生物群中进行研究具有高度创新性。这项工作意义重大 因为分子生物标志物定义了饮食摄入量、微生物群组成之间的关系， 将确定宿主基因表达和儿童健康结果。这些宿主微生物分子指纹 将使患者驱动的精准医疗能够优化婴儿生长并降低儿童肥胖风险。