1. Sarah N. Taylor, MD and Carol L Wagner, MD Department of Pediatrics
Preterm Infant Gut Permeability Differs By Human Milk versus Formula Exposure
Sarah N. Taylor, MD and Carol L Wagner, MD
Department of Pediatrics

2. Preterm Infant Gut
Infants born as early as 23 weeks gestation (37-41 weeks is full term)
Fetal intestine length doubles from 25 to 40 weeks gestation
Therefore, this now occurs in the extra-uterine environment

3. Continuum of Gut Development and Maturation
Amniotic Fluid Human Milk
Phase V
Phase IV
Phase III
Phase II
Phase I
Fetal Development
Birth
Adapted from Wagner CL et al; Clinic Rev Allerg Immunol 2008

4. Preterm Infant Feeding
Must nourish infant
Intravenous nutrition available but associated with infection and damage to liver
Feeding the immature gut then required
Formula (cow’s milk-based) associated with damage to the gut and mortality
Therefore, breastmilk (mother’s milk) is the gold standard
Also have donor human milk
Donated from screened donors and then pasteurized like cow’s milk
Tested to have no growth of bacteria

5. Intestinal Permeability Measurement
Sugar Absorption Tests
Lactulose
Paracellular absorption
Mannitol
Intracellular absorption
Provide standard doses
Similar distribution and
renal excretion
Measure ratio in urine

6. Preterm Infant Intestinal Permeability by Feeding Type
Infants fed majority of feeds as human milk (minimal formula intake) have significantly
lower intestinal permeability than those fed minimal/none human milk (majority or all
formula feedings)
Taylor SN et al 2008

7. Current Study Preterm infant human milk diet requires fortification
Fortifier choices
Two are concentrated formula (cow’s milk base)
One is concentrated donor milk (complete human milk diet)
What is the difference in intestinal permeability between a complete human milk diet and a mixed human milk/cow’s milk fortifier diet?

8. First Days of Human milk feeds
Study Conduction
Birth
Feed Initiation
Enrollment
Postnatal 1-3 d
First Days of Human milk feeds
Visit 1
Postnatal 2-4 d
Pre-fortification
(pre- intervention)
Visit 2
Postnatal 6-8 d
Post-fortification
(post-intervention)
Visit 3
Postnatal d
Full feeds
Visit 4
Postnatal d

9. Intestinal Permeability Gut Microbiota
Feeding Type
Intestinal Permeability
Gut Microbiota
Vaginal or cesarean section delivery
Gestational age at birth <27, 27-30, weeks
Postnatal days
Antibiotic exposure

10. Mother’s milk fed more
Likely to be Type 2 or 3
Cong X et al 2016

11. Gregory KE et al 2016

12. Microbiota Comparisons
By feeding type (3)
Over time between groups and within groups
By degree of prematurity at birth <27, 27-30, weeks
Hypotheses:
Microbiota diversity will increase over time
Infants receiving human milk only diet will demonstrate microbiota more similar to term, breastfed infant
Higher bifidobacterium bifidum
Lower proteobacteria

13. Expertise Needed A few examples Analysis of how many samples?
Collecting 792 (1 at each of 4 time points for 198 infants)
Opportunities in metagenomics compared to 16S sequencing?
Methods to optimize identification of bifidobacterium?