We propose the first comprehensive evaluation of the intestinal microbiota in premature infants at risk for necrotizing enterocolitis (NEC). The overall goals respond to objectives of the NIH Funding Opportunity Announcement, which include: 1. gaining a better understanding of the bacterial ecology of the infant intestine, 2. understanding how commensal organisms work to dampen inappropriate inflammatory responses of the enterocyte, 3. find methods to better identify prematurely born infants at highest risk of NEC in order to enter them into clinical trials of preventive therapy. Three hypotheses will be tested: Hypothesis 1. Infants who subsequently develop NEC establish a high risk microbiota that can be distinguished from a low risk pattern. This will be accomplished using unique newly developed molecular techniques;Hypothesis 2. High-risk- for- NEC stool microbiota patterns are associated with altered inflammatory mediator markers. This will be evaluated using correlations with plasma samples as well as buccal smears, which may offer the potential for determination of early biomarkers using a relatively non-invasive approach;Hypothesis 3. The high risk fecal microbiota and inflammatory patterns are associated with other morbidities such as hospital acquired sepsis, chronic lung disease and neurological injury. Here we will correlate intestinal microbial patterns and inflammatory marker patterns with non intestinal diseases associated with inflammatory processes in the neonate such hospital acquired sepsis, chronic lung disease and neurologic damage such as intracranial hemorrhage (IVH) and periventricular leukomalacia (PVL). This research will provide new information on the relationship between intestinal microbiota, gut derived systemic inflammation, NEC and other neonatal morbidities. Significance: At the completion of this project a relationship between NEC and stool microbiota will be found: This may consist of finding an individual causative pathogen or more likely, a quantitative or qualitative pattern that is consistently associated with the presence or absence of NEC. This will guide us in the choice of safe and effective preventative measures, such as choice of correct probiotic. In addition, finding inflammation-related markers using a non-invasive technique such as fecal analysis or tongue scraping to determine individuals at highest risk for the development of NEC will improve our chances of only using this preventative therapy for those individuals at highest risk for the disease PUBLIC HEALTH REVELANCE: The relevance of this research is that at the completion of this project a relationship between NEC, one of the most devastating diseases seen in premature infants, and stool microbes will be found: This may consist of finding an individual causative pathogen or more likely, a quantitative or qualitative pattern that is consistently associated with the presence or absence of NEC. This will guide us in the choice of safe and effective preventative measures and result in an enhanced ability to find those at highest risk by use of non-invasive techniques such as fecal analysis or tongue swabs, rather than the more invasive and painful blood based analysis.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD059143-05
Application #
8392292
Study Section
Special Emphasis Panel (ZHD1-DSR-A (18))
Program Officer
Grave, Gilman D
Project Start
2008-12-17
Project End
2013-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
5
Fiscal Year
2013
Total Cost
$297,298
Indirect Cost
$94,364
Name
University of Florida
Department
Pediatrics
Type
Schools of Medicine
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Neu, Josef (2014) Probiotics and necrotizing enterocolitis. Clin Perinatol 41:967-78
Sharma, R; Kraemer, D F; Torrazza, R M et al. (2014) Packed red blood cell transfusion is not associated with increased risk of necrotizing enterocolitis in premature infants. J Perinatol 34:858-62
Douglas-Escobar, Martha; Elliott, Elizabeth; Neu, Josef (2013) Effect of intestinal microbial ecology on the developing brain. JAMA Pediatr 167:374-9
Sharma, Renu; Hudak, Mark Lawrence (2013) A clinical perspective of necrotizing enterocolitis: past, present, and future. Clin Perinatol 40:27-51
Torrazza, Roberto Murgas; Neu, Josef (2013) The altered gut microbiome and necrotizing enterocolitis. Clin Perinatol 40:93-108
Murgas Torrazza, Roberto; Li, Nan; Young, Christopher et al. (2013) Pilot study using proteomics to identify predictive biomarkers of necrotizing enterocolitis from buccal swabs in very low birth weight infants. Neonatology 104:234-42
Mai, Volker; Young, Christopher Michael; Ukhanova, Maria et al. (2011) Fecal microbiota in premature infants prior to necrotizing enterocolitis. PLoS One 6:e20647
Mshvildadze, Maka; Neu, Josef; Shuster, Jonathan et al. (2010) Intestinal microbial ecology in premature infants assessed with non-culture-based techniques. J Pediatr 156:20-5
Sharma, Renu; Tepas 3rd, Joseph J (2010) Microecology, intestinal epithelial barrier and necrotizing enterocolitis. Pediatr Surg Int 26:11-21
Mshvildadze, Maka; Neu, Josef (2010) The infant intestinal microbiome: friend or foe? Early Hum Dev 86 Suppl 1:67-71

Showing the most recent 10 out of 12 publications