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. 2016 Apr 1;62(7):863-870.
doi: 10.1093/cid/ciw016. Epub 2016 Jan 19.

A Necrotizing Enterocolitis-Associated Gut Microbiota Is Present in the Meconium: Results of a Prospective Study

Fardou H Heida  1   2 , Anne G J F van Zoonen  1 , Jan B F Hulscher  1 , Bastiaan J C Te Kiefte  1 , Rianne Wessels  1 , Elisabeth M W Kooi  3 , Arend F Bos  3 , Hermie J M Harmsen  2 , Marcus C de Goffau  2
Affiliations

A Necrotizing Enterocolitis-Associated Gut Microbiota Is Present in the Meconium: Results of a Prospective Study

Fardou H Heida et al. Clin Infect Dis. .

Abstract

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.

Keywords: gut microbiota; microbiome profiling; necrotizing enterocolitis.

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Comment in

  • Clostridium Species Identification by 16S rRNA Pyrosequencing Metagenomics.
    Cassir N, Benamar S, Croce O, La Scola B. Cassir N, et al. Clin Infect Dis. 2016 Jun 15;62(12):1616-8. doi: 10.1093/cid/ciw203. Epub 2016 Apr 3. Clin Infect Dis. 2016. PMID: 27045121 No abstract available.
  • Reply to Cassir et al.
    Heida FH, van Zoonen AG, Hulscher JB, Te Kiefte BJ, Wessels R, Kooi EM, Bos AF, Harmsen HJ, de Goffau MC. Heida FH, et al. Clin Infect Dis. 2016 Jun 15;62(12):1618-20. doi: 10.1093/cid/ciw205. Epub 2016 Apr 3. Clin Infect Dis. 2016. PMID: 27045124 No abstract available.

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