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Neonatal GI Physiology & NEC

Neonatal GI Physiology & NEC 5: Predicting Necrotizing Enterocolitis, Gut Health, and Oral Feeding

105 - Differential effect of formula, donor human milk and maternal milk on small intestinal organoid growth

Saturday, April 29, 2023

3:30 PM – 6:00 PM ET

Poster Number: 105
Publication Number: 105.237

Lauren Smith, Yale School of Medicine, New Haven, CT, United States; Chino K. Eke, Yale University, New Haven, CT, United States; Liza Konnikova, Yale School of Medicine, New Haven, CT, United States

Presenting Author(s)

LS

Lauren Smith, BS (she/her/hers)

Medical Student
Yale School of Medicine
New Haven, Connecticut, United States

Background: Necrotizing enterocolitis (NEC) is a severe gastrointestinal complication of prematurity. Though the pathogenesis of NEC remains unclear, there is strong evidence showing that one of the largest risk factors for developing NEC aside from prematurity is formula exposure, while feeding with maternal milk is protective. Donor milk, while also shown to have a protective effect, confers significantly less risk reduction than maternal milk, possibly due to pasteurization which may reduce the quantity of bioactive proteins present.

Objective:

Using small intestinal organoids (enteroids) derived from fetal tissue of a gestational age similar to an extremely preterm infant, this study aims to assess the effect of diets common in preterm infants on intestinal epithelial growth with the hope of further elucidating the role diet plays in modifying risk for NEC.

Design/Methods:

Enteroids were cultured for 7 days in 4 different diet conditions: maternal milk, donor milk, formula, or organoid growth media (OGM). All diets were diluted 1:40 with OGM and enteroids were cultured in a 48 well plate with 3 technical replicates of each condition. 4x images were captured daily on an Echo Revolve Digital Microscope and enteroids were quantified via manual counting and area measurement at days 4 and 7.

Results:

Maternal milk supplementation supported the highest number of generated enteroids compared to all other conditions, with a statistically significant difference in the number of enteroids per well in the maternal milk group compared to both the donor milk and formula groups on days 4 and 7. While initially there was a greater number of enteroids generated by OGM compared to donor milk and formula, suggesting a delay in enteroid generation in those conditions, by day 7 there was no significant difference in enteroid count between these three groups. Interestingly, maternal milk-fed and formula-fed enteroids remained small in size with no significant increase in average enteroid area between days 4 and 7, while donor milk-fed organoids grew to a similar size as OGM control organoids.

Conclusion(s):

In summary, this study suggests that while maternal milk supports the generation of the greatest numbers of enteroids compared to all other treatments, donor milk supports the most growth in the size of individual enteroids compared to maternal milk and formula.