Brain-Gut Microbiome-Visceral Adiposity Relationships in Multiethnic Adults

多种族成人的脑肠微生物群与内脏肥胖关系

• 批准号: 8970516
• 负责人: LINDA CHANG
• 金额: $ 23.75万
• 依托单位: UNIVERSITY OF HAWAII AT MANOA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8970516
• 关键词: Abdomen; Accounting; Adipose tissue; Adult; Anisotropy; Anxiety; Bacteria; Behavior; Body Composition; Brain; Brain Chemistry; Brain Diseases; Brain imaging; Carbohydrates; Cessation of life; Characteristics; Chemistry; Cognition; Cognitive; Cohort Studies; Communities; Data; Diet; Dietary Practices; Dietary intake; Diffusion Magnetic Resonance Imaging; Dual-Energy X-Ray Absorptiometry; Eating; Eating Behavior; Emotional; Epidemic; Epidemiologic Studies; Ethnic group; European; Fatty acid glycerol esters; Food; Frequencies; Functional disorder; Funding Opportunities; Future; Glutamates; Glutamine; Goals; Hawaii; Hawaiian population; Hepatic; Homeostasis; Hormones; Image; Impaired cognition; Inflammation; Intake; Intervention; Intervention Studies; Intra-abdominal; Japanese American; Japanese Population; Knowledge; Lead; Liver; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Malignant Neoplasms; Measurement; Measures; Metabolic; Micronutrients; Molecular; Moods; Morphology; N-acetylaspartate; Neuronal Injury; Neurons; Obesity; Participant; Performance; Phylogeny; Prevention; Probiotics; Program Research Project Grants; Protons; Public Health; Questionnaires; Reporting; Research; Risk; Scanning; Signal Transduction; Structure; Subgroup; Technology; Translational Research; United States National Institutes of Health; Ursidae Family; Visceral; Weight; Weight maintenance regimen; Woman; abdominal fat; base; brain morphology; brain volume; cognitive function; energy balance; ethnic minority population; gut microbiota; improved; innovation; men; microbial; microbial community; microbiome; morphometry; mortality; myoinositol; neurochemistry; neuroinflammation; novel; obesity treatment; premature; prevent; programs; public health relevance; rRNA Genes; saturated fat; trait; white matter

 DESCRIPTION (provided by applicant): Body fatness contributes to a substantial proportion of the premature deaths in the U.S., including 15-20% of cancer mortality. The impact is greater among ethnic minorities because they tend to accumulate more visceral fat that bears a higher metabolic risk. The unabated obesity epidemic and lack of sustainable weight control interventions may improve if we understand obesity better as a "brain disease" and a dysregulation of the brain-gut-adiposity axis. The brain is long known to regulate energy homeostasis based on fuel availability signals originating from the gut and adipose tissue but appears to be altered structurally and metabolically in obesity, which may perpetuate the positive energy balance. Obesity has been associated with a smaller brain volume, deleterious neurochemical imbalance, and cognitive impairment. Obesity-prone eating behaviors and anabolic dietary composition have been similarly associated with brain alterations. Also, the colonic microbiota has recently been shown to be associated with brain chemistry, anxiety behaviors and adiposity. Leveraging recent advances in brain and body composition imaging and in molecular technology, we propose to investigate the brain-gut-adiposity axis for novel inter-relationships across brain imaging characteristics, gut microbial profiles and visceral fat content. We will add a brain MRI study to an ongoing Program Project grant, where we are assessing visceral and hepatic fat with whole-body DXA and abdominal MRI in 2,000 women and men of five ethnic groups from the Multiethnic Cohort Study to examine the relationship of visceral/liver fat to gut microbiota phylogeny based on 16S rRNA gene sequencing and to habitual dietary intakes using eating behavior and food frequency questionnaires. We will conduct brain MR imaging (MRI) and proton MR spectroscopy (1H MRS) to assess brain imaging characteristics (macro- and micro-structural morphology, neurometabolite levels) in a subgroup of 100 program project participants from three ethnic groups (Japanese American, Native Hawaiian, white) in Hawaii. Our specific aims are to determine the association of these structural and neurochemical brain traits with (1) visceral and hepatic fat content, (2) eating behaviors and dietary composition, and (3) gut microbial community profiles. We hypothesize that lower total and regional brain volumes, higher levels of glial metabolite myoinositol, indicative of inflammation, and lower neuronal metabolite N-acetylaspartate will be associated with greater amounts of visceral and liver fat, a higher tendency for obesity-prone eating behaviors (external, emotional, routinely restrained eating) and anabolic dietary composition (high in refined carbohydrates, saturated fat), and altered and less diverse gut microbial profiles Cognitive functions will be assessed with the NIH Toolbox and correlated to brain MRI, dietary intake, and gut bacteria measurements. This innovative line of research has a great potential to lead to more effective and better targeted obesity intervention strategies.

 描述(由申请人提供)：在美国，身体肥胖是导致过早死亡的很大比例，包括15%-20%的癌症死亡。在少数民族中影响更大，因为他们往往积累更多的内脏脂肪，承担更高的代谢风险。如果我们更好地将肥胖理解为一种“脑部疾病”和大脑-肠道-肥胖轴的失调，肥胖症的流行有增无减，缺乏可持续的体重控制干预措施，可能会有所改善。众所周知，大脑根据来自肠道和脂肪组织的燃料供应信号来调节能量动态平衡，但在肥胖时，大脑的结构和代谢似乎发生了变化，这可能会维持正能量平衡。肥胖与大脑体积变小、有害的神经化学失衡和认知障碍有关。肥胖倾向的饮食行为和合成代谢的饮食结构与大脑的变化也有类似的联系。此外，结肠微生物区系最近被证明与大脑化学、焦虑行为和肥胖症有关。利用大脑和身体成分成像和分子技术的最新进展，我们建议研究大脑-肠道-肥胖轴，以寻找大脑成像特征、肠道微生物谱和内脏脂肪含量之间的新的相互关系。我们将在正在进行的计划项目拨款中增加一项脑MRI研究，在该项目中，我们使用全身DXA和腹部MRI对来自多民族队列研究的5个民族的2000名女性和男性进行内脏和肝脏脂肪评估，以基于16S rRNA基因测序检查内脏/肝脏脂肪与肠道微生物区系发展的关系，并使用饮食行为和食物频率问卷检查内脏/肝脏脂肪与习惯性饮食摄入量的关系。我们将进行脑磁共振成像(MRI)和质子磁共振波谱(1HMRS)，以评估来自夏威夷三个种族(日裔美国人、夏威夷原住民和白人)的100名项目参与者的脑成像特征(宏观和微观结构形态、神经代谢物水平)。我们的具体目标是确定这些结构和神经化学大脑特征与(1)内脏和肝脏脂肪含量，(2)饮食行为和饮食组成，以及(3)肠道微生物群落组成的相关性。我们假设，较低的总和局部脑容量，较高水平的神经胶质代谢物肌醇(指示炎症)和较低的神经元代谢物N-乙酰天冬氨酸将与更多的内脏和肝脏脂肪，更容易肥胖的饮食行为(外部、情绪，常规节食)和合成代谢饮食组成(高精制碳水化合物，饱和脂肪)的倾向，以及改变和较少多样化的肠道微生物谱认知功能将使用NIH工具箱进行评估，并与大脑MRI、饮食摄入量和肠道细菌测量相关。这一创新的研究路线具有巨大的潜力，可以带来更有效、更有针对性的肥胖干预策略。