The hygiene hypothesis suggests that the absence of endotoxin exposure leads to an unfavorable Th1/Th2 balance. A controlled antigen exposure during infancy may help establish a Th1/Th2 balance that blocks the onset or progression of asthma. Lactobacillus is a bacterium found in many foods in the typical pediatric diet, and is used as a supplement to prevent diarrhea. Due to the safety, feasibility and early promising results in preventing atopic dermatitis, Lactobacillus is an ideal bacterium to use as an exposure to test the hygiene hypothesis. We hypothesize that such an exposure may block or delay development of early markers of asthma. Using a randomized placebo-controlled trial design, we will measure the effect of a 6-month daily exposure of Lactobacillus, as an infant formula supplement, on immune system and asthma development during the first 3 years of life. We will measure the effect of the antigen exposure on the presence and time to presentation of (1) early clinical markers for asthma development (frequent wheezing, wheezing without colds, rhinitis, and atopic dermatitis); (2) early immunologic markers for asthma development (eosinophilia, IgE); and (3) development of a T-helper phenotype (Th-1 vs Th-2). We will characterize the Th phenotype by measuring the whole blood lymphocyte response to stimulants, focusing Th1 (IFN-gamma, IL-12) and Th2 cytokines (IL-10, IL-4, IL-13), as well as real-time reverse transcriptase polymerase chain reaction (RT-PCR) with PCR amplification (TaqMan) to quantify RNA transcripts. Clinical and immunologic markers will be measured up to 3 years of age. Adherence will be assessed using diaries, pill count, and Lactobacillus stool cultures. We will use intention-to-treat analysis and will control for the impact of family, environmental, diet, and demographic factors on outcomes using multivariate regression and survival analysis techniques. We expect that when compared to controls, subjects receiving Lactobacillus will have decreased and delayed development of markers for asthma, and a greater likelihood of developing a Th1 phenotype. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL080074-04
Application #
7102572
Study Section
Special Emphasis Panel (ZAI1-KLW-I (M6))
Program Officer
Noel, Patricia
Project Start
2004-09-27
Project End
2009-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
4
Fiscal Year
2006
Total Cost
$482,857
Indirect Cost
Name
University of California San Francisco
Department
Pediatrics
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Cabana, Michael D; McKean, Michelle; Caughey, Aaron B et al. (2017) Early Probiotic Supplementation for Eczema and Asthma Prevention: A Randomized Controlled Trial. Pediatrics 140:
McKean, Michelle; Caughey, Aaron B; Leong, Russell E et al. (2015) The Timing of Infant Food Introduction in Families With a History of Atopy. Clin Pediatr (Phila) 54:745-51
Fujimura, Kei E; Slusher, Nicole A; Cabana, Michael D et al. (2010) Role of the gut microbiota in defining human health. Expert Rev Anti Infect Ther 8:435-54
Cox, Michael J; Huang, Yvonne J; Fujimura, Kei E et al. (2010) Lactobacillus casei abundance is associated with profound shifts in the infant gut microbiome. PLoS One 5:e8745
Yoo, Jennifer; Tcheurekdjian, Haig; Lynch, Susan V et al. (2007) Microbial manipulation of immune function for asthma prevention: inferences from clinical trials. Proc Am Thorac Soc 4:277-82
Cabana, Michael D; McKean, Michelle; Wong, Angela R et al. (2007) Examining the hygiene hypothesis: the Trial of Infant Probiotic Supplementation. Paediatr Perinat Epidemiol 21 Suppl 3:23-8
Cabana, Michael D; Shane, Andi L; Chao, Cewin et al. (2006) Probiotics in primary care pediatrics. Clin Pediatr (Phila) 45:405-10