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Mechanisms of vitamin B(12) absorption in breast-fed infants
1Department of Nutrition university of California, Davis, California 95616, USA.
Insights
Haptocorrin (HC) in breast milk may facilitate vitamin B12 absorption in infants until their intrinsic factor (IF) system matures. This study investigated infant vitamin B12 absorption mechanisms, suggesting a dual role for HC and IF.
Area of Science:
- Neonatal nutrition
- Gastrointestinal physiology
- Vitamin B12 metabolism
Background:
- Vitamin B12 absorption mechanisms in infants are not well understood.
- Investigating the roles of haptocorrin (HC) from milk and intrinsic factor (IF) in neonatal vitamin B12 uptake.
Purpose of the Study:
- To determine if HC or IF facilitates vitamin B12 delivery to intestinal cells in neonates.
- To compare infant absorption pathways with adult mechanisms.
Main Methods:
- Binding assays using Caco-2 cells with HC-[57Co]vitamin B12 and IF-[125I]vitamin B12.
- ELISA for fecal IF in breast-fed infants.
- Ligand blot analysis of intestinal brush border membrane vesicles (BBMV) for IF and HC receptors.
- PCR for IF receptor gene transcript identification.
Main Results:
- Limited binding of HC and IF to Caco-2 cells observed.
- HC showed affinity for low molecular weight proteins in fetal intestinal BBMV; IF bound to a 240 kDa protein.
- IF receptor gene transcript present in fetal intestine and Caco-2 cells.
- Increasing fecal IF excretion noted in breast-fed infants over time.
Conclusions:
- An intrinsic factor (IF)-dependent vitamin B12 absorption pathway is likely functional in infants.
- Early-life IF levels may be insufficient for significant vitamin B12 absorption.
- Haptocorrin (HC) might be crucial for vitamin B12 absorption in neonates until the IF system matures.
Objectives:
The mechanisms of vitamin B(12) absorption in infants are unknown. We investigated whether haptocorrin (HC), a vitamin B(12) -binding protein in human milk, facilitates vitamin B(12) absorption during the neonatal period or if it occurs by a process similar to that in adults involving another vitamin B(12) -binding protein, intrinsic factor (IF).
Methods:
To determine whether HC or IF can deliver vitamin B(12) to the enterocyte, binding studies using Caco-2 intestinal cells in culture and purified human milk HC-[ (57)Co]vitamin B(12) or [(125)I]IF-vitamin B(12) were performed. Determination of IF secretion by infant stomach was investigated by a competitive ELISA on fecal extracts from breast-fed infants. Determination of receptors specific for IF-vitamin B(12) or HC-vitamin B(12) in infant intestine was achieved by ligand blot analysis using isolated brush border membrane vesicles (BBMV) from fetal and adult intestine and Caco-2 cells. PCR was performed to identify the IF receptor gene transcript in Caco-2 cells and fetal intestine.
Results:
Limited binding of both HC and IF to Caco-2 cells was observed; however, HC displayed affinity to low molecular weight proteins in BBMV from fetal intestine and Caco-2 cells while IF showed affinity for a 240 kDa protein in BBMV from fetal intestine and Caco-2 cells. IF receptor gene transcript was identified in fetal intestine and Caco-2 cells. An increase in IF excretion from breast-fed infants throughout early life was observed.
Conclusions:
An IF-dependent vitamin B(12) absorption mechanism appears to be in place in breast-fed infants. However, IF levels may be too low in early life to participate in vitamin B(12) absorption; therefore, haptocorrin may mediate vitamin B(12) absorption until the absorption function can be taken over by a more mature IF system.