Grant Abstract: Early Childhood Diet, Growth, Gut Microbiome And Lung Health in Cystic Fibrosis

Grant Number: 1R01DK109692-02S1
PI Name: Huichuan
Project Title: Early Childhood Diet, Growth, Gut Microbiome And Lung Health in Cystic Fibrosis

Abstract: Cystic fibrosis (CF) is one of the most common life-shortening genetic diseases. It is characterized by pancreatic insufficiency, resulting in malnutrition and obstructive lung diseases with recurrent respiratory 20 years.
This administrative supplement, in response to PA-16-319, proposes a pilot study to gain new knowledge in probiotic supplementation and its associations with intestinal inflammation and gut microbiome in young children CF by utilizing resources available from an ongoing multi-center prospective study referred to as the FIRST study (the Parent Study) that is being funded by NIH-R01DK109692 (9/2016-8/2021).
The FIRST study was launched in 2012 to investigate the potential benefits and risks of exclusive breastfeeding in the first 2 years of life and to identify optimal feeding for infants with CF. It is being conducted in 6 CF centers in 5 states (WI, IL, IN, MA, UT) to enroll 200 infants with CF diagnosed through newborn screening. In 2014, follow up of the FIRST cohort was extended to 6 years of age and two complementary studies, breast milk composition and gut microbiome, were initiated. As of 3/31/17, 162 infants have been enrolled at 1.4±0.8 months of age. We anticipate to complete enrollment of 200 infants with CF by early 2018.
Probiotics, commonly used as dietary supplements, are modestly effective in treating acute viral gastroenteritis and preventing antibiotic associated diarrhea in healthy children, according to the American Academy of Pediatrics. In addition, probiotics have the potential to promote healthy intestinal flora and modulate gut immunity. However, studies on probiotics in patients with CF are sparse, especially during the first 2 years of life. In this administrative supplement, we propose to investigate probiotic supplementation in children with CF younger than 2 years of age with three specific aims:
Aim 1: Characterize probiotic use and test 2 hypotheses: a) probiotic supplementation is more prevalent in children with CF than in healthy children, and b) probiotic supplementation in children with CF is influenced by parents’ and healthcare providers’ beliefs.
Aim 2: Examine associations of probiotic use to intestinal inflammation and symptoms and test 2 hypotheses: a) fecal calprotectin, a marker of intestinal inflammation, differs between probiotic users and non-users, and b) probiotic supplementation reduces intestinal symptoms associated with malabsorption due to CF.
Aim 3: Compare fecal microbiome by 16S rRNA between probiotic users and non-users and test 2 hypotheses: a) probiotic supplementation alters the diversity and relative abundance of fecal microbiome, and b) probiotic strains correlate with taxonomic characteristics of fecal microbiome.
Results generated from accomplishing this grant will fill in a significant gap of knowledge with the potential to advance clinical care and improve outcomes in children with CF.

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