TY - JOUR
T1 - A Necrotizing Enterocolitis-Associated Gut Microbiota Is Present in the Meconium
T2 - Results of a Prospective Study
AU - Heida, Fardou H
AU - van Zoonen, Anne G J F
AU - Hulscher, Jan B F
AU - Te Kiefte, Bastiaan J C
AU - Wessels, Rianne
AU - Kooi, Elisabeth M W
AU - Bos, Arend F
AU - Harmsen, Hermie J M
AU - de Goffau, Marcus C
N1 - © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected].
PY - 2016/4/1
Y1 - 2016/4/1
N2 - BACKGROUND: Anomalous intestinal microbiota development is supposedly associated with development of necrotizing enterocolitis (NEC). Our aim in this study was to identify the intestinal microbiota of patients at risk for NEC.METHODS: In a prospective trial that investigated prognostic factors for development of NEC in high-risk neonates (NTR4153), 11 NEC cases were gestational age/birthweight matched with controls (ratio of 1:2). Feces were collected twice a week. We used the first feces sample of each patient (meconium), as well as the last 2 feces samples prior to development of NEC. DNA was extracted, and the bacterial 16S rRNA genes were analyzed on a MiSeq sequencer.RESULTS: The presence and abundance of Clostridium perfringens (8.4%) and Bacteroides dorei (0.9%) in meconium were increased in neonates who developed NEC compared with controls (0.1% and 0.2%; both species, P < .001). In post-meconium samples, the abundance of staphylococci became negatively associated with NEC development (P = .1 and P = .01 for consecutive samples); Clostridium perfringens continued to be more prevalent in NEC cases. Early enteral feeding and, in particular, breast milk were correlated with an increase in lactate-producing bacilli in post-meconium samples (ρ = -0.45; P = .004).CONCLUSIONS: A NEC-associated gut microbiota can be identified in meconium samples; C. perfringens continues to be associated with NEC from the first meconium till just before NEC onset. In contrast, in post-meconium, increased numbers of staphylococci were negatively associated with NEC. These findings suggest causality but this causality should be verified in trials of induced infection in animals, targeted antibiotics, and/or probiotics.CLINICAL TRIALS REGISTRATION: CALIFORNIA trial, registered under trial number NTR4153 in the Dutch Trial Registry.
AB - BACKGROUND: Anomalous intestinal microbiota development is supposedly associated with development of necrotizing enterocolitis (NEC). Our aim in this study was to identify the intestinal microbiota of patients at risk for NEC.METHODS: In a prospective trial that investigated prognostic factors for development of NEC in high-risk neonates (NTR4153), 11 NEC cases were gestational age/birthweight matched with controls (ratio of 1:2). Feces were collected twice a week. We used the first feces sample of each patient (meconium), as well as the last 2 feces samples prior to development of NEC. DNA was extracted, and the bacterial 16S rRNA genes were analyzed on a MiSeq sequencer.RESULTS: The presence and abundance of Clostridium perfringens (8.4%) and Bacteroides dorei (0.9%) in meconium were increased in neonates who developed NEC compared with controls (0.1% and 0.2%; both species, P < .001). In post-meconium samples, the abundance of staphylococci became negatively associated with NEC development (P = .1 and P = .01 for consecutive samples); Clostridium perfringens continued to be more prevalent in NEC cases. Early enteral feeding and, in particular, breast milk were correlated with an increase in lactate-producing bacilli in post-meconium samples (ρ = -0.45; P = .004).CONCLUSIONS: A NEC-associated gut microbiota can be identified in meconium samples; C. perfringens continues to be associated with NEC from the first meconium till just before NEC onset. In contrast, in post-meconium, increased numbers of staphylococci were negatively associated with NEC. These findings suggest causality but this causality should be verified in trials of induced infection in animals, targeted antibiotics, and/or probiotics.CLINICAL TRIALS REGISTRATION: CALIFORNIA trial, registered under trial number NTR4153 in the Dutch Trial Registry.
KW - necrotizing enterocolitis
KW - gut microbiota
KW - microbiome profiling
KW - PRETERM INFANTS
KW - CLOSTRIDIUM-DIFFICILE
KW - PREMATURE-INFANTS
KW - COLONIZATION
U2 - 10.1093/cid/ciw016
DO - 10.1093/cid/ciw016
M3 - Article
C2 - 26787171
SN - 1058-4838
VL - 62
SP - 863
EP - 870
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 7
ER -