Necrotizing
enterocolitis and the prophylactic use of
probiotics
E van Niekerk, PhD
Department of Global Health, Division of Human Nutrition
EARLY COLONIZATION IS A KEY LIFE EVENT
EARLY COLONIZATION IN
PRETERM INFANTS
S Matamoros - 2013
5 PLoS One. 2016; 11(6): e0158498.
Distribution of relative abundance of taxa between feeding types during the first 30 days of life.
Cong X, Xu W, Janton S, Henderson WA, Matson A, et al. (2016) Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender. PLOS ONE 11(4):
e0152751. https://doi.org/10.1371/journal.pone.0152751 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.
0152751
Pediatric Research 2014
Milk-Oriented Microbiota (MOM)
THE ENTEROMAMMARY PATHWAY
• Although the precise mechanisms of this transfer inside the body have not
• been completely unveiled so far, several findings already suggest how it probably works. Itseems that dendritic cells – among whose tasks is the detection of potentially harmful microorganisms
• – serve as transport vehicles. These cells are able to pervade the intestinal wall –
• while leaving its barrier function intact –, take up non-pathogenic bacteria from inside the gut and
• feed them in the lymphatic and blood circulation through which they finally reach the milk
• producing mammary gland. Beside dendritic cells, macrophages (belonging to the white blood
• cells) might play a similar role. “Our findings and those of other research groups have gathered
• evidence that, firstly, there is a pathway linking the mother’s gut with the mammary gland during
• lactation period and that, secondly, dendritic and possibly other mononuclear cells serve as
• transport vehicles that carry these live intestinal bacteria via this pathway.”
8 Fernández et al., 2012
HUMAN MILK OLIGOSACCHARIDES
Prebiotics are non-digestible food
ingredients that stimulate the growth or activity of bacteria in the digestive system
which are beneficial to human health
• Human milk contains a unique amount of
complex oligosaccharides (5-8g/l)
HMO PROPERTIES
• Impacts on the intestinal micro-biota
• Prebiotic “fuel” or MORE?
• Un-metabolized
• Anti-Adhesive effect
Pathophysiology 21 (2014) 3–12
PREVENTION: FORMULA VS BREAST MILK
• Formula feeding increases short-term growth
• Greater risk of developing NEC when compared
to infants who received donor milk
Paediatrics and Child Health, 2015
PROBIOTICS PROTECT AGAINST NEC
• Promoting colonization of the gut with beneficial organisms
• Preventing colonization by pathogens
• Improving the maturity and function of gut mucosal
barrier
• Modulating the immune system to the advantage of the host
Ann Nutr Metab 2012;61:160-174
Outcome: NEC II/III
EVIDENCE-BASED CHILD HEALTH: A COCHRANE REVIEW JOURNAL 9:3: 584–671 (2014)
PLOS ONE , 2017
COCHRANE REVIEW JOURNAL 9:3: 584–671 (2014)
Outcome: Mortality
NEC related mortality
21 EVIDENCE-BASED CHILD HEALTH: A COCHRANE REVIEW JOURNAL 9:3: 584–671 (2014)
EVIDENCE-BASED CHILD HEALTH: A COCHRANE REVIEW JOURNAL 9:3: 584–671 (2014)
Outcome: Sepsis
To evaluate the efficacy of probiotics in reducing the incidence and severity of
NEC in premature very-low
birth weight infants that are
exposed to HIV
STUDY DESIGN
• A double blinded, placebo-controlled, RCT
• L rhamnosus GG & B Infantis
STUDY POPULATION
• <34 weeks gestation
• <1 250g
• HIV exposed and unexposed
• Born at Tygerberg Children’s Hospital
NEC per HIV group
HIV-exposed HIV-unexposed
Probiotic (n=37)
Placebo (n=37)
P<0.05 Probiotic (n=54)
Placebo (n=56)
P<0.05
NEC n=2 n=2 0.045* n=1 n=4 0.36
NEC Bell’s I 2 (5%) None 1 (2%) 2 (4%)
NEC Bell’s III
None 2 (5%) None 2 (4%)
NEC incidence Tygerberg Hospital South Africa (2014)
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5
Probiotic Placebo
Bell’s I Bell’s III
p=0.029*
J tropical Med. 2014
J. Nutr. 144: 1227–1233, 2014.