The role of feeding (breast milk versus formula) on a Necrotizing enterocolitis-associated microbiota.

Wessels, R. (Rianne) (2015) The role of feeding (breast milk versus formula) on a Necrotizing enterocolitis-associated microbiota. thesis, Medicine.

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Abstract

Background Necrotizing enterocolitis (NEC) is the most severe gastrointestinal (GI) emergency in premature neonates. Unfortunately, the exact pathophysiology of NEC remains poorly understood. Bacterial colonization is believed to play a pivotal role in the development of NEC. Thereby, it is hypothesized that breastfeeding plays an important role in protecting the intestine against NEC, via colonization with “gut-protecting bacteria”. Unfortunately, there is no clear consensus about the relation between feeding, the intestinal microbiota and subsequent NEC development. Therefore, the aim of this study was to investigate the relation between feeding (breast milk versus formula) and a NEC-associated microbiota. Methods This study was conducted from a prospective trial, aiming to investigate prognostic factors for the development of NEC in high-risk neonates (NTR4153). Ten NEC cases were gestational-age/birth-weight matched with 12 controls from the same cohort. For the present analysis, we used the first sample of the study of each patient (meconium), as well as the last two feces samples prior to NEC. We extracted bacterial DNA and the bacterial 16S rRNA gene sequences were analyzed on a MiSeq sequencer. To investigate the relation between the intestinal microbiota and the neonatal feeding regime, we collected data concerning the feeding regime (i.e. start of enteral feeding, type of feeding, the amount of feeding and moment of full enteral feeding) from the nursery files. Results In meconium samples, we found an association with Clostridium Perfringens and Bacteroides Dorei and NEC development (both≤0.001). In post-meconium samples, abundance of staphylococci were negatively associated with NEC (p=0.05 and p=0.01). The importance of early commencement of enteral nutrition and breastfeeding were linked with this finding. A significant association with NEC development in the duration of time between birth and start of enteral feeding (p=0.02) was found (NEC: median 7h, range 2- 10; Controls: median 3h, range 2 – 8). The sooner the start of enteral feeding the higher the amount of lactate producing bacilli (staphylococci: ρ=-0.34; p=0.03). In post-meconium samples, the amount of breastfeeding as a percentage of the total amount of feeding, is associated with a decrease in Enterobacteriaceae numbers (ρ=-0.28; p=0.038) and an increase in the abundance of lactate producing bacilli (ρ=-0.32; p=0.01). Thereby, the amount of breastfeeding just before NEC onset were found to be negatively associated with NEC development (p=0.04). Conclusion This study demonstrates an association between Clostridium perfringens, Bacteroides dorei and NEC development. This association is already present directly after birth. On the other hand, in post meconium samples, abundances of staphylococci became negatively associated with NEC, which were influenced by early enteral feeding and breastfeeding. In post meconium samples, (early) enteral feeding with breastfeeding expedites the shift from a more Enterobacteriaceae dominated microbiota into one, which is more, populated by lactate producing bacilli, in particular staphylococci. This renders neonates less susceptible to NEC development.

Item Type:	Thesis (Thesis)
Supervisor name:	Hulscher, dr. J.B.F. and Heida, drs. F.H.
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 11:06
Last Modified:	25 Jun 2020 11:06
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/2611

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