Anemia and Iron Status are Predictors of Gut Microbiome Composition and Metabolites in Infants and Children in Rural Kenya

Abstract

BackgroundThe gut microbiome in childhood has been linked to inflammation and immune function, but very little is known about the differences in the gut microbiome comparing anemic and nonanemic infants and children in Sub‐Saharan Africa.DesignIn a cross sectional study in infants (4–6 month‐olds) and preschool children (2–5 yr‐olds) (n=134) in rural Kenya, we measured haemoglobin (Hb) and iron status, analyzed gut microbiota composition by 16S pyrosequencing and targeted real‐time PCR (qPCR), and measured fecal calprotectin (a marker of intestinal inflammation) and fecal short chain fatty acids.ResultsAnemia rates were 67% and 46% among the infants and children, respectively. The infant gut microbiome consisted of the phyla Actinobacteria (64.3% of reads), Firmicutes (22.4%; including 4.7% Lactobacillus), Bacteroidetes (8.9%; including 3.6% Bacteroides and 4.3% Prevotella), and Proteobacteria (4.1%; including 3.3% Escherichia/Shigella); and was highly dominated by the family of Bifidobacteriaceae, contributing 63.0% of the total 16S rRNA. In contrast, the 2–5 y‐olds had an adult‐like gut microbiota profile with low abundances of Proteobacteria and aerobic gram negative bacteria but high abundances of Firmicutes and Bacteroides. There was no significant effect of baseline anemia status on phylogenetic diversity among the infants, but there were significant differences in taxa between anemic and nonanemic infants: nonanemic infants harbored lower abundances of Prevotella (2.0% vs 4.5%, p=0.014), whereas, they showed higher abundances of Actinomycetales (0.14% vs 0.09%, p=0.004) and Streptococcus (6.3% vs 3.9%, p=0.023). Among the infants, there was a positive correlation between Hb and Roseburia (r2= 0.146; p=0.03), a positive correlation between Hb and sum of pathogenic E.coli (r2=0.139; p=0.047; n=101), a negative correlation between serum transferrin receptor and the sum of pathogenic E.coli (r2=−0.158, p=0.024) and greater numbers of Clostridium difficile in anemic than in nonanemic infants (p=0.022). Among the older children, there was a positive correlation between Hb and Clostridia cluster XIV (r2=0.469, p=0.001) and Clostridia cluster IV (r2=0.381, p=0.01), a negative correlation between Hb and the sum of pathogenic E.coli (r2=0.402; p=0.008), a negative correlation between serum ferritin and the sum of pathogenic E.coli (r2=0.390; p=0.042) and lower abundance of Clostridia cluster XIV and IV in anemic vs. nonanemic children (p= 0.002 and 0.006, respectively). There were no significant differences in fecal calprotectin in anemic vs. nonanemic infants or children. In anemic infants and children, acetate and propionate concentrations were higher and butyrate was lower than in nonanemic infants and children.ConclusionsIn infancy, higher Hb and better iron status predict higher amounts of pathogenic E.coli. In contrast, among older children, higher Hb and better iron status predict lower amounts of pathogenic E.coli. Anemic infants and children do not have greater gut inflammation, but have lower fecal butyrate concentrations, compared to nonanemic children. Thus, relationships between anemia, iron status and pathogenic gut microbiota differ by age in rural Kenya.Support or Funding InformationThis project was supported by the Eunice Kennedy Shriver National Institute Of Child Health & Human Development under grant number U01HD064921, the European Union's Seventh Framework Programme (Fp7/2007‐2013) under grant agreement number 211484 and the ETH Zurich, Switzerland.