Brain-Gut Microbiome-Visceral Adiposity Relationships in Multiethnic Adults

 描述（由申请人提供）：身体肥胖是美国过早死亡的很大一部分原因，包括15-20%的癌症死亡率。这种影响在少数民族中更大，因为他们倾向于积累更多的内脏脂肪，从而承担更高的代谢风险。如果我们更好地理解肥胖是一种“脑部疾病”和脑-肠-肥胖轴的失调，那么有增无减的肥胖流行病和缺乏可持续的体重控制干预措施可能会有所改善。长期以来，人们都知道大脑会根据来自肠道和脂肪组织的燃料可用性信号来调节能量稳态，但在肥胖症中，大脑的结构和代谢似乎会发生变化，这可能会使正能量平衡永久化。肥胖与脑体积变小、有害的神经化学物质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组成也与大脑的改变类似。此外，结肠微生物群最近被证明与大脑化学，焦虑行为和肥胖有关。利用大脑和身体组成成像和分子技术的最新进展，我们建议调查大脑-肠道-肥胖轴，以获得大脑成像特征、肠道微生物概况和内脏脂肪含量之间的新型相互关系。我们将在一项正在进行的计划项目资助中增加一项脑MRI研究，在该研究中，我们正在使用全身DXA和腹部MRI评估来自多种族队列研究的5个种族的2，000名女性和男性的内脏和肝脏脂肪，以检查内脏/肝脏脂肪与肠道微生物群的关系基于16 S rRNA基因测序，并使用饮食行为和食物频率问卷调查习惯性饮食摄入量。我们将对来自夏威夷三个种族（日裔美国人、夏威夷土著人、白色人）的100名项目参与者进行脑MR成像（MRI）和质子MR波谱（1H MRS），以评估脑成像特征（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）肠道微生物群落特征的关联。我们假设，较低的总脑容量和局部脑容量，较高水平的神经胶质代谢物肌醇，指示炎症，以及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，肥胖倾向的饮食行为的更高的倾向（外部，情绪化，常规限制饮食）和合成代谢饮食组成（高精制碳水化合物、饱和脂肪）和改变的和较少多样性的肠道微生物谱将用NIH ESTA评估认知功能，并将其与脑MRI、饮食摄入和肠道细菌测量相关联。这项创新的研究有很大的潜力，可以导致更有效和更有针对性的肥胖干预策略。

 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.