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Effects of iron supplementation on growth, gut microbiota, metabolomics and cognitive development of rat pups
Erica E Alexeev1, Xuan He1,2, Carolyn M Slupsky1,2
1Department of Nutrition, University of California, Davis, CA, United States America.
Insights
Excess iron supplementation in infant rats negatively impacted cognitive development, potentially due to metabolic changes and gut microbiota alterations. Further research is needed to understand these effects.
Area of Science:
- Nutritional Science
- Developmental Biology
- Microbiology
Background:
- Iron deficiency is common in infants, necessitating iron supplementation.
- However, excessive iron in replete infants may negatively impact growth, cognition, and health.
- This study investigates the effects of iron supplementation in infant rats.
Purpose of the Study:
- To determine the impact of iron supplementation on cognitive development in normal and growth-restricted infant rats.
- To explore the metabolic and gut microbial changes associated with iron supplementation.
- To assess the dose-dependent effects of iron on iron status and development.
Main Methods:
- Infant rats (normal and growth-restricted) received daily iron (30 or 150 μg/d) from birth to postnatal day 20.
- Cognitive functions were evaluated using T-maze and passive avoidance tests.
- Hematology, tissue iron, plasma metabolome, and colonic microbial ecology were analyzed.
Main Results:
- Iron supplementation increased iron status in a dose-dependent manner without affecting growth.
- High-dose iron supplementation impaired passive avoidance in normal rats.
- Excess iron altered plasma and liver metabolome (increased 3-hydroxybutyrate, decreased amino acids, urea, myo-inositol) and gut microbiota composition.
Conclusions:
- Excess iron adversely affects cognitive development in infant rats.
- Altered metabolism and gut microbiota shifts may underlie these cognitive deficits.
- Findings highlight potential risks of iron supplementation in iron-replete infants.
Background:
Iron deficiency is common during infancy and therefore iron supplementation is recommended. Recent reports suggest that iron supplementation in already iron replete infants may adversely affect growth, cognitive development, and morbidity.
Methods:
Normal and growth restricted rat pups were given iron daily (30 or 150 μg/d) from birth to postnatal day (PD) 20, and followed to PD56. At PD20, hematology, tissue iron, and the hepatic metabolome were measured. The plasma metabolome and colonic microbial ecology were assessed at PD20 and PD56. T-maze (PD35) and passive avoidance (PD40) tests were used to evaluate cognitive development.
Results:
Iron supplementation increased iron status in a dose-dependent manner in both groups, but no significant effect of iron on growth was observed. Passive avoidance was significantly lower only in normal rats given high iron compared with controls. In plasma and liver of normal and growth-restricted rats, excess iron increased 3-hydroxybutyrate and decreased several amino acids, urea and myo-inositol. While a profound difference in gut microbiota of normal and growth-restricted rats was observed, with iron supplementation differences in the abundance of strict anaerobes were observed.
Conclusion:
Excess iron adversely affects cognitive development, which may be a consequence of altered metabolism and/or shifts in gut microbiota.
