Anemia in infancy is associated with alterations in systemic metabolism and microbial structure and function in a sex-specific manner: an observational study

Slupsky, Carolyn M.; Casapía, Martin; Zavaleta, Nelly; McClorry, Shannon; Llanos Cuentas, Elmer Alejandro; Lönnerdal, Bo

dc.contributor.author	McClorry, Shannon
dc.contributor.author	Zavaleta, Nelly
dc.contributor.author	Llanos Cuentas, Elmer Alejandro
dc.contributor.author	Casapía, Martin
dc.contributor.author	Lönnerdal, Bo
dc.contributor.author	Slupsky, Carolyn M.
dc.date.accessioned	2018-11-08T19:39:20Z
dc.date.available	2018-11-08T19:39:20Z
dc.date.issued	2018
dc.identifier.uri	https://hdl.handle.net/20.500.12866/3938
dc.description.abstract	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.	en_US
dc.language.iso	eng
dc.publisher	Oxford University Press
dc.relation.ispartofseries	American Journal of Clinical Nutrition
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	Iron deficiency	en_US
dc.subject	Anemia	en_US
dc.subject	Infant	en_US
dc.subject	Development	en_US
dc.subject	Mitochondrial dysfunction	en_US
dc.subject	Sex difference	en_US
dc.subject	Fecal microbiome	en_US
dc.subject	Metabolome	en_US
dc.title	Anemia in infancy is associated with alterations in systemic metabolism and microbial structure and function in a sex-specific manner: an observational study	en_US
dc.type	info:eu-repo/semantics/article
dc.identifier.doi	https://doi.org/10.1093/ajcn/nqy249
dc.subject.ocde	https://purl.org/pe-repo/ocde/ford#3.03.04
dc.relation.issn	1938-3207