The Impact of Formula fortified with Milk Fat Globule Membrane on the Neonatal Intestine
Authors: Bhinder Ganive , Garcia Cyrielle , Gräf Franziska , Crowley Shauna , Bosman Else , Ryz Natasha , Berkmann Julia , Dyer Roger , Innis Sheila , Vallance Bruce 
Published: November 2023

Background

Breastmilk provides the ideal nutrient source during development. However, in some cases it is not available in adequate amounts, if at all (especially following premature delivery), to the developing infant resulting in a need for formula feeding. As achieving appropriate growth during this early time is essential for proper development and protection from noxious stimuli, there is a need for the composition of formula to mimic that of breastmilk as closely as possible. Fat in breastmilk, a major source of energy for the newborn, contains a unique and very complex triple membrane structure referred to as the Milk Fat Globule Membrane (MFGM) resulting in strikingly large fat molecules (average size of 5μm in human milk). Surprisingly, the fat component in formula is derived from vegetable sources rather than MFGM, which differ greatly in size and composition. Interestingly, although studies in several adult models of infection and inflammation have attributed protective effects to MFGM supplementation, its role in the newborn intestine and its development has not thoroughly been explored.

Objective

To examine the effects of Milk Fat Globule Membrane (MFGM) on postnatal development of the small intestine and colon.

Methods

Rat pups were artificially reared using the pup‐in‐a‐cup model to examine the effects of MFGM (1.2 or 6 mg/mL) supplementation on early intestinal development. Rat pups underwent gastronomy at postnatal day (PD) 5 and were supplemented with formula containing soy (control formula) or MFGM+soy until PD15, at which point they were euthanized along with mother reared littermates, resulting in three groups. Small (jeujunal, ileal) and large intestinal (distal colon) samples were collected for histological assessment and immunohistochemistry (IHC).

Results

Although no overt differences were noted in pup weight or overall length of the small or large intestine at PD15 between the three groups, histological assessment revealed significant changes in the epithelial architecture along the length of the intestine (jejunum, ileum and colon). MFGM supplementation resulted in significant dose dependent changes at the intestinal surface, resulting in crypt depths similar to those recorded in mother reared (MR) pups at PD15. IHC analysis of intestinal sections revealed similar positive staining between MFGM and MR pups for major cell types within the epithelium (goblet cells and enterocytes), rates of cell proliferation, and tight junction proteins.

Conclusion

MFGM normalizes many aspects of intestinal development similar to that observed in mother reared littermates. Its supplementation in formula may be beneficial in neonates who do not have access to breast milk, particularly pre‐term infants to accelerate intestinal development.

Support or Funding Information

Ganive Bhinder is funded by a Canadian Institutes of Health Research Phd Studentship and University of British Columbia 4 year fellowship.

Milk Fat Globule Membrane for this study was provided by Mead Johnson Nutrition.