title: Intestinal microbial ecology and environmental factors affecting necrotizing enterocolitis.
abstract: Necrotizing enterocolitis (NEC) is the most devastating intestinal disease affecting preterm infants. In addition to being associated with short term mortality and morbidity, survivors are left with significant long term sequelae. The cost of caring for these infants is high. Epidemiologic evidence suggests that use of antibiotics and type of feeding may cause an intestinal dysbiosis important in the pathogenesis of NEC, but the contribution of specific infectious agents is poorly understood. Fecal samples from preterm infants ≤ 32 weeks gestation were analyzed using 16S rRNA based methods at 2, 1, and 0 weeks, prior to diagnosis of NEC in 18 NEC cases and 35 controls. Environmental factors such as antibiotic usage, feeding type (human milk versus formula) and location of neonatal intensive care unit (NICU) were also evaluated. Microbiota composition differed between the three neonatal units where we observed differences in antibiotic usage. In NEC cases we observed a higher proportion of Proteobacteria (61%) two weeks and of Actinobacteria (3%) 1 week before diagnosis of NEC compared to controls (19% and 0.4%, respectively) and lower numbers of Bifidobacteria counts and Bacteroidetes proportions in the weeks before NEC diagnosis. In the first fecal samples obtained during week one of life we detected a novel signature sequence, distinct from but matching closest to Klebsiella pneumoniae, that was strongly associated with NEC development later in life. Infants who develop NEC exhibit a different pattern of microbial colonization compared to controls. Antibiotic usage correlated with these differences and combined with type of feeding likely plays a critical role in the development of NEC.
authors.affiliation: Department of Pediatrics, College of Medicine University of Florida, Gainesville, Florida, United States of America.
authors.forename: Roberto Murgas
authors.initials: RM
authors.lastname: Torrazza
authors.affiliation: Department of Epidemiology, College of Public Health and Health Professions and College of Medicine and Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Maria
authors.initials: M
authors.lastname: Ukhanova
authors.affiliation: Department of Epidemiology, College of Public Health and Health Professions and College of Medicine and Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pediatrics University of Florida College of Medicine, Jacksonville, Florida, United States of America.
authors.forename: Renu
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Pediatrics University of Florida College of Medicine, Jacksonville, Florida, United States of America.
authors.forename: Mark Lawrence
authors.initials: ML
authors.lastname: Hudak
authors.affiliation: Department of Pediatrics, College of Medicine University of Florida, Gainesville, Florida, United States of America.
authors.forename: Josef
authors.initials: J
authors.lastname: Neu
authors.affiliation: Department of Epidemiology, College of Public Health and Health Professions and College of Medicine and Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Volker
authors.initials: V
authors.lastname: Mai
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001644:Bifidobacterium / Q000145:classification / Q000235:genetics; D044822:Biodiversity; D016022:Case-Control Studies; D016000:Cluster Analysis; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy / Q000209:etiology* / Q000382:microbiology; D004777:Environment; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy / Q000209:etiology* / Q000382:microbiology; D007422:Intestines / Q000187:drug effects / Q000382:microbiology* / Q000473:pathology*; D008297:Male; D054892:Metagenome; D064307:Microbiota; D012336:RNA, Ribosomal, 16S; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents; D012336:RNA, Ribosomal, 16S