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Anemia in infancy is associated with alterations in systemic metabolism and microbial structure and function in a
Shannon McClorry1, Nelly Zavaleta2, Alejandro Llanos2
1Departments of Nutrition.
Insights
Early-life anemia, especially iron-deficiency anemia (IDA), impacts infant metabolism and gut microbes. Sex-specific differences in metabolic pathways and microbial function were observed, potentially explaining lasting cognitive deficits.
Area of Science:
- Nutritional Science
- Microbiome Research
- Pediatric Health
Background:
- Early-life anemia, particularly iron-deficiency anemia (IDA), is linked to adverse metabolic, developmental, and cognitive outcomes.
- These outcomes can persist into adulthood, highlighting the importance of early intervention.
Purpose of the Study:
- To investigate metabolic and fecal microbial alterations in male and female infants with anemia and IDA.
- To explore sex-specific differences in these alterations.
Main Methods:
- Collected stool and serum samples from 95 infants at 12 months of age.
- Assessed fecal microbiome using 16S rRNA gene sequencing.
- Quantified fecal and serum metabolomes using 1H-nuclear magnetic resonance.
Main Results:
- Anemia prevalence was 64%, higher in males and often due to IDA.
- Anemia associated with decreased tricarboxylic acid cycle metabolites; IDA impacted microbiome structure and function, reducing butyrate-producing bacteria.
- Sex-specific metabolic differences observed, with IDA males showing higher 4-hydroxyphenyllactate and putrescine, and IDA females showing higher leucine and valine.
Conclusions:
- Sexually dimorphic differences suggest greater mitochondrial dysfunction and oxidative stress in males.
- Microbial alterations may contribute to observed metabolic changes.
- Metabolic pathway differences in each sex offer potential mechanisms for cognitive deficits.
Background:
Anemia is a term that describes low hemoglobin concentrations and can result from micronutrient deficiencies, infection, or low birth weight. Early-life anemia, particularly iron-deficiency anemia (IDA) is associated with several negative metabolic, developmental, and cognitive outcomes, some of which persist into adulthood.
Objective:
The aim of this study was to investigate alterations in systemic metabolism and fecal microbial diversity and functionality associated with anemia and IDA in male and female infants from Iquitos, Peru.
Design:
Cross-sectional stool and serum samples were collected from 95 infants (53 boys and 42 girls) at 12 mo of age. The fecal microbiome was assessed by using 16S ribosomal RNA gene sequencing, and the fecal and serum metabolomes were quantified using 1H-nuclear magnetic resonance.
Results:
The prevalence of anemia was 64%, with a greater proportion of anemia in male infants attributed to iron deficiency. Metabolically, anemia was associated with decreased concentrations of tricarboxylic acid cycle metabolites in both sexes (males: succinate, P = 0.031; females: fumarate, P = 0.028). In addition, anemic male infants exhibited significantly lower serum concentrations of several amino acids compared with nonanemic male infants. Although no specific structural or functional differences in the microbiota were observed with anemia in general, likely due the heterogeneity of its etiology, IDA affected the microbiome both structurally and functionally. Specifically, the abundance of butyrate-producing bacteria was lower in IDA subjects of both sexes than in nonanemic, non-iron-deficient subjects of the same sex (females: Butyricicoccus, P = 0.041; males: Coprococcus, P = 0.010; Roseburia, P = 0.027). IDA male infants had higher concentrations of 4-hydroxyphenyllactate (P < 0.001) and putrescine (P = 0.042) than those without IDA, whereas IDA female infants exhibited higher concentrations of leucine (P = 0.011) and valine (P = 0.003).
Conclusions:
Sexually dimorphic differences associated with anemia and IDA are suggestive of greater mitochondrial dysfunction and oxidative stress in male infants compared with female infants, and alterations in microbial structure and function may further contribute. Differences in metabolic pathways associated with anemia and IDA in each sex point to potential mechanisms for the associated lasting cognitive deficits. This trial is registered at clinicaltrials.gov as NCT03377777.
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