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Human Milk Fortification Increases Bnip3 Expression Associated With Intestinal Cell Death In Vitro
William Diehl-Jones1, Alyssa Archibald, Joseph W Gordon
1*Faculty of Health Disciplines, Athabasca University, Athabasca, Alberta †Department of Biological Sciences, University of Manitoba ‡Department of Human Anatomy and Cell Science §Faculty of Nursing ||Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada.
A bovine-based human breast milk fortifier (HMF) increases intestinal cell death by upregulating BCL2/adenovirus E1B 19 kDa protein-interacting protein (Bnip3). Misoprostol, a prostaglandin analogue, may reduce this HMF-induced cell death.
Area of Science:
- Gastroenterology
- Cell Biology
- Neonatal Research
Background:
- Human breast milk fortifiers (HMF) are crucial for preterm infant nutrition.
- The specific impact of bovine-based HMF on intestinal cell function requires further elucidation.
Purpose of the Study:
- To investigate the in vitro effects of a bovine-based HMF on human intestinal cells.
- To determine the role of BCL2/adenovirus E1B 19 kDa protein-interacting protein (Bnip3) in HMF-induced intestinal cell death.
- To evaluate the potential protective effect of misoprostol against HMF-induced cell damage.
Main Methods:
- Human intestinal cells were cultured and exposed to in vitro-digested human breast milk (BM) with or without HMF.
- Measurements included intracellular oxidation, cell damage/death, and Bnip3 expression (transcript and protein levels).
- Misoprostol was used to assess its rescue effect on HMF-induced cell death.
Main Results:
- HMF significantly increased intracellular oxidation, cell damage, and cell death in enterocytes compared to controls.
- Bnip3 transcript and protein levels were significantly elevated following HMF exposure.
- Transfection with Bnip3 also increased enterocyte cell death, which was mitigated by a nonfunctional Bnip3 splice variant.
Conclusions:
- HMF enhances intestinal Bnip3 expression in vitro, leading to increased cell death.
- Misoprostol shows promise as a therapeutic agent to reduce HMF-induced intestinal cell death.
