Childhood infection and prevention of obesity

儿童感染与肥胖的预防

• 批准号: 7764738
• 负责人: Julie Parsonnet
• 金额: $ 74.5万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-25 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7764738
• 关键词: Address; Adolescence; Affect; Attention; Child; Childhood; Chronic; Chronic Disease; Cohort Studies; Communicable Diseases; Conceptions; Data; Desire for food; Development; Differentiation and Growth; Disease; Documentation; Energy Metabolism; Epidemic; Etiology; Family Sizes; Food; Habits; Health; Helicobacter Infections; Helicobacter pylori; Herpesviridae; Human; Hygiene; Infection; Infection prevention; Infectious Agent; Inflammatory; Life; Link; Lipolysis; Measures; Methods; Microbe; Monitor; Obesity; Overweight; Parents; Pilot Projects; Preventive; Principal Investigator; Reporting; Rest; Series; Shapes; Signs and Symptoms; Testing; Weight; Weight Gain; adipocyte differentiation; cytokine; malignant stomach neoplasm; novel vaccines; obesity in children; prenatal; programs; public health relevance; trend

DESCRIPTION (provided by applicant): Obesity is epidemic in the U.S. with almost 20% of children considered obese. The dramatic rise in overweight and obesity over the last 40 years coincides with equally dramatic decreases in childhood infections. Although these inverse trends-rising obesity and declining infection-could be only coincidentally related, we postulate that the relationship is, in fact, causal. Infectious agents are the most intimate and constant exposure in human existence. This fact is brought to our attention annually as each year, new infectious agents are unexpectedly identified as causal factors in chronic disease. With respect to obesity, infections can both increase energy expenditure and decrease appetite through a variety of direct and indirect mechanisms. Infection-induced cytokines can also affect adipocyte differentiation, growth and lipolysis. Since these are all critical factors in human weight gain, it is axiomatic-though currently quite controversial-to assume that infections may reduce weight in U.S. children. We hypothesize that frequent, chronic and/or severe prenatal and childhood infection prevent weight gain, overweight and obesity in children. Secondarily, we will address the hypothesis that early acquisition of specific chronic infections-e.g.,herpesviruses and H. pylori infection-protect against obesity. We plan to test these hypotheses in a series of pilot studies, followed by a longitudinal cohort study that follows young children from conception through at least 5 years and, ultimately to adolescence and adulthood, to determine how infectious diseases shape body habitus. Determination of infection in children will rely on two interrelated exposure measures: monitoring and reporting of daily symptoms and signs by parents, and documentation of seroconversion to a large panel of microbes. We will also explore mechanisms by which infection might alter weight gain including effects on resting energy expenditure, circulating inflammatory cytokines, and adipocytokine levels. The discovery of H. pylori in the 1980's demonstrated how accepted paradigms of disease causation can be astonishingly wrong. For obvious reasons, the study of obesity (like the study of stomach cancer before 1990) has focused on food. Although we are not revolutionary enough to say that food is immaterial to weight, we do propose that a significant proportion of the increase in weight in U.S. children over the last 40 years is related not to bad habits but to healthy, uninfected lives. This idea-if proved trued-would certainly prove transformative, potentially changing overall conceptions of weight, health and disease in childhood. PUBLIC HEALTH RELEVANCE: There has been a 4-fold increase in obesity U.S. children over the last 40 years. Simultaneously, infections of childhood are disappearing due to changes in family size, improvements in hygiene, the addition of new vaccines, and other preventive health measures. This study intends to establish methods and collect preliminary data to determine whether decreases in childhood infection are linked to development of obesity.

描述（由申请人提供）：肥胖在美国很普遍，近 20% 的儿童被认为肥胖。过去 40 年来，超重和肥胖人数急剧增加，与此同时，儿童感染率也同样急剧下降。尽管这些相反的趋势——肥胖率上升和感染率下降——可能只是巧合相关，但我们假设这种关系实际上是因果关系。传染源是人类存在中最亲密、最持续的暴露。这一事实每年都会引起我们的注意，因为每年都会出人意料地发现新的传染源是慢性病的致病因素。对于肥胖，感染可以通过各种直接和间接机制增加能量消耗并降低食欲。感染诱导的细胞因子也会影响脂肪细胞的分化、生长和脂肪分解。由于这些都是人类体重增加的关​​键因素，因此假设感染可能会减轻美国儿童的体重是不言而喻的（尽管目前颇有争议）。我们假设频繁、慢性和/或严重的产前和儿童感染可预防儿童体重增加、超重和肥胖。其次，我们将提出这样一个假设：早期获得特定慢性感染（例如疱疹病毒和幽门螺杆菌感染）可以预防肥胖。我们计划通过一系列试点研究来检验这些假设，随后进行纵向队列研究，跟踪幼儿从受孕到至少 5 年，最终到青春期和成年期，以确定传染病如何影响身体习惯。儿童感染的确定将依赖于两项相互关联的暴露措施：父母对日常症状和体征的监测和报告，以及大量微生物血清转化的记录。我们还将探讨感染可能改变体重增加的机制，包括对静息能量消耗、循环炎症细胞因子和脂肪细胞因子水平的影响。 20 世纪 80 年代幽门螺杆菌的发现表明，公认的疾病因果关系范式可能是错误的。出于显而易见的原因，对肥胖的研究（就像 1990 年之前对胃癌的研究一样）一直集中在食物上。尽管我们还没有足够的革命性来证明食物对体重无关紧要，但我们确实提出，过去 40 年来美国儿童体重增加的很大一部分与坏习惯无关，而是与健康、未受感染的生活有关。这个想法如果被证明是正确的，肯定会带来变革，有可能改变儿童时期体重、健康和疾病的整体概念。 公共健康相关性：过去 40 年来，美国儿童肥胖症增加了 4 倍。与此同时，由于家庭规模的变化、卫生条件的改善、新疫苗的添加以及其他预防性卫生措施，儿童感染正在消失。本研究旨在建立方法并收集初步数据，以确定儿童感染的减少是否与肥胖的发展有关。