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Published on: July 28, 2023
A Necrotizing Enterocolitis-Associated Gut Microbiota Is Present in the Meconium: Results of a Prospective Study
Fardou H Heida1,2, Anne G J F van Zoonen1, Jan B F Hulscher1
1Department of Pediatric Surgery.
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.
Insights
Necrotizing enterocolitis (NEC) is linked to abnormal gut bacteria. Specific bacteria like Clostridium perfringens were found in higher amounts in infants who developed NEC, even in meconium samples.
Area of Science:
- Neonatal research
- Microbiome studies
- Gastroenterology
Background:
- Anomalous intestinal microbiota development is linked to necrotizing enterocolitis (NEC) in neonates.
- Identifying the gut microbiota in high-risk infants is crucial for understanding NEC development.
Purpose of the Study:
- To identify the intestinal microbiota composition in neonates at risk for NEC.
- To investigate the association between specific microbial profiles and NEC development.
Main Methods:
- Prospective trial (NTR4153) involving high-risk neonates.
- Fecal samples (meconium and pre-NEC onset) collected and analyzed for bacterial 16S rRNA genes using MiSeq sequencing.
- Gestational age/birthweight matched NEC cases and controls.
Main Results:
- Increased Clostridium perfringens and Bacteroides dorei in meconium of NEC cases compared to controls (P < .001).
- Staphylococci negatively associated with NEC in post-meconium samples; C. perfringens remained prevalent in NEC cases.
- Early enteral feeding, especially breast milk, correlated with increased lactate-producing bacilli.
Conclusions:
- A NEC-associated gut microbiota is identifiable in meconium.
- C. perfringens is consistently associated with NEC from meconium to pre-onset; staphylococci show a negative association post-meconium.
- Findings suggest causality, warranting further investigation through animal models, antibiotics, or probiotics.
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