NCT01111864.

Iron (Fe) deficiency anemia is a global health concern and Fe fortification and supplementation are common corrective strategies. Fe is essential not only for the human host but also for nearly all gut bacteria. We studied the impact of Fe deficiency and Fe repletion on the gut microbiota in rats. Weanling rats were fed an Fe-deficient diet for 24 d and then repleted for 13 d with FeSO₄ (n = 15) or electrolytic Fe (n = 14) at 10 and 20 mg Fe · kg diet⁻¹. In addition, one group of rats (n = 8) received the Fe-deficient diet and one group (n = 3) received a Fe-sufficient control diet for all 37 d. Fecal samples were collected at baseline and after the depletion and repletion periods, and colonic tissues were examined histologically. Microbial metabolite composition in cecal water was measured and fecal samples were analyzed for microbial composition with temporal temperature gradient gel electrophoresis and qPCR. Compared to Fe-sufficient rats, Fe-deficient rats had significantly lower concentrations of cecal butyrate (-87%) and propionate (-72%) and the abundance of dominant species was strongly modified, including greater numbers of lactobacilli and Enterobacteriaceae and a large significant decrease of the Roseburia spp./E. rectale group, a major butyrate producer. Repletion with 20 mg FeSO₄ · kg diet⁻¹ significantly increased cecal butyrate concentrations and partially restored bacterial populations compared to Fe-deficient rats at endpoint. The effects on the gut microbiota were stronger in rats repleted with FeSO₄ than in rats repleted with electrolytic Fe, suggesting ferrous Fe may be more available for utilization by the gut microbiota than elemental Fe. Repletion with FeSO₄ significantly increased neutrophilic infiltration of the colonic mucosa compared to Fe-deficient rats. In conclusion, Fe depletion and repletion strongly affect the composition and metabolic activity of rat gut microbiota.

Hepcidin regulation by competing stimuli such as infection and iron deficiency has not been studied in infants and it’s yet unknown whether hepcidin regulatory pathways are fully functional in infants. In this cross-sectional study including 339 Kenyan infants aged 6.0±1.1 months (mean±SD), we assessed serum hepcidin-25, biomarkers of iron status and inflammation, and fecal calprotectin. Prevalence of inflammation, anemia, and iron deficiency was 31%, 71%, 26%, respectively. Geometric mean (±SD) serum hepcidin was 6.0 (±3.4) ng/mL, and was significantly lower in males than females. Inflammation (C-reactive protein and interleukin-6) and iron status (serum ferritin, zinc protoporphyrin and soluble transferrin receptor) were significant predictors of serum hepcidin, explaining nearly 60% of its variance. There were small, but significant differences in serum hepcidin comparing iron deficient anemic (IDA) infants without inflammation to iron-deficient anemic infants with inflammation (1.2 (±4.9) vs. 3.4 (±4.9) ng/mL; P<0.001). Fecal calprotectin correlated with blood/mucus in the stool but not with hepcidin. Similarly, the gut-linked cytokines IL-12 and IL-17 did not correlate with hepcidin. We conclude that hepcidin regulatory pathways are already functional in infancy, but serum hepcidin alone may not clearly discriminate between iron-deficient anemic infants with and without infection. We propose gender-specific reference values for serum hepcidin in iron-replete infants without inflammation.

BackgroundBifidobacteria is one of the major gut commensal groups found in infants. Their colonization is commonly associated with beneficial effects to the host through mechanisms like niche occupation and nutrient competition against pathogenic bacteria. Iron is an essential element necessary for most microorganisms, including bifidobacteria and efficient competition for this micronutrient is linked to proliferation and persistence. For this research we hypothesized that bifidobacteria in the gut of iron deficient infants can efficiently sequester iron. The aim of the present study was to isolate bifidobacteria in fecal samples of iron deficient Kenyan infants and to characterize siderophore production and iron internalization capacity.ResultsFifty-six bifidobacterial strains were isolated by streaking twenty-eight stool samples from Kenyan infants, in enrichment media. To target strains with high iron sequestration mechanisms, a strong iron chelator 2,2-dipyridyl was supplemented to the agar media. Bifidobacterial isolates were first identified to species level by 16S rRNA sequencing, yielding B. bifidum (19 isolates), B. longum (15), B. breve (11), B. kashiwanohense (7), B. pseudolongum (3) and B. pseudocatenulatum (1). While most isolated bifidobacterial species are commonly encountered in the infantile gut, B. kashiwanohense was not frequently reported in infant feces. Thirty strains from culture collections and 56 isolates were characterized for their siderophore production, tested by the CAS assay. Siderophore activity ranged from 3 to 89% siderophore units, with 35 strains (41%) exhibiting high siderophore activity, and 31 (36%) and 20 (23%) showing intermediate or low activity. The amount of internalized iron of 60 bifidobacteria strains selected for their siderophore activity, was in a broad range from 8 to118 μM Fe. Four strains, B. pseudolongum PV8-2, B. kashiwanohense PV20-2, B. bifidum PV28-2a and B. longum PV5-1 isolated from infant stool samples were selected for both high siderophore activity and iron internalization.ConclusionsA broad diversity of bifidobacteria were isolated in infant stools using iron limited conditions, with some strains exhibiting high iron sequestration properties. The ability of bifidobacteria to efficiently utilize iron sequestration mechanism such as siderophore production and iron internalization may confer an ecological advantage and be the basis for enhanced competition against enteropathogens.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-014-0334-z) contains supplementary material, which is available to authorized users.

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