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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
3R01HD063142-02S1
Application #
8250240
Study Section
Special Emphasis Panel (ZRG1-BCMB-A (51))
Program Officer
Raiten, Daniel J
Project Start
2009-09-25
Project End
2014-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
2
Fiscal Year
2011
Total Cost
$44,800
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Ley, Catherine; Pischel, Lauren; Parsonnet, Julie (2017) Triclosan and triclocarban exposure and thyroid function during pregnancy-A randomized intervention. Reprod Toxicol 74:143-149
Ribado, Jessica V; Ley, Catherine; Haggerty, Thomas D et al. (2017) Household triclosan and triclocarban effects on the infant and maternal microbiome. EMBO Mol Med 9:1732-1741
Ley, Catherine; Sanchez, Maria de la Luz; Mathur, Ankur et al. (2016) Stanford's Outcomes Research in Kids (STORK): a prospective study of healthy pregnant women and their babies in Northern California. BMJ Open 6:e010810
Poole, Angela C; Pischel, Lauren; Ley, Catherine et al. (2016) Crossover Control Study of the Effect of Personal Care Products Containing Triclosan on the Microbiome. mSphere 1:
Contopoulos-Ioannidis, Despina G; Ley, Catherine; Wang, Wei et al. (2016) Effect of long-term antibiotic use on weight in adolescents with acne. J Antimicrob Chemother 71:1098-105
Lankester, Joanna; Patel, Chirag; Cullen, Mark R et al. (2013) Urinary triclosan is associated with elevated body mass index in NHANES. PLoS One 8:e80057
Suh, Gina; Ley, Catherine; Parsonnet, Julie (2012) Infectious diseases in children and body mass index in young adults. Emerg Infect Dis 18:1490-2