Stable iron (58Fe) isotopic measurements in Kenyan toddlers during 3 months of iron supplementation demonstrate that half of the iron absorbed is lost.

Increased iron loss may reduce the effectiveness of iron supplementation. The objective of this study was to determine if daily oral iron supplementation increases iron loss, measured using a stable isotope of iron (58Fe). We enrolled and dewormed 24 iron-depleted Kenyan children, 24-27 months of age, whose body iron was enriched and equilibrated with 58Fe given at least 1 year earlier. Over 3 months of supplementation (6 mg iron/kg body weight [BW]/day), mean (±SD) iron absorption was 1.10 (±0.28) mg/day. During supplementation, 0.55 (±0.36) mg iron/day was lost, equal to half of the amount of absorbed iron. Supplementation did not increase faecal haem/porphyrin or biomarkers of enterocyte damage and gut or systemic inflammation. Using individual patient data, we examined iron dose, absorption and loss among all available long-term iron isotopic studies of supplementation. Expressed in terms of body weight, daily iron loss was correlated significantly with iron absorption (Pearson's r = 0.66 [95% confidence interval 0.48-0.78]) but not with iron dose (r = 0.16 [95% CI -0.10-0.40]). The results of this study indicate that iron loss is increased with daily oral iron supplementation and may blunt the efficacy of iron supplements in children. This study was registered at ClinicalTrials.gov as NCT04721964.

Prebiotics increase iron absorption and reduce the adverse effects of iron on the gut microbiome and inflammation: a randomized controlled trial using iron stable isotopes in Kenyan infants.

BACKGROUND: Iron fortificants tend to be poorly absorbed and may adversely affect the gut, especially in African children. OBJECTIVE: We assessed the effects of prebiotic galacto-oligosaccharides/fructo-oligosaccharides (GOS/FOS) on iron absorption and gut health when added to iron-fortified infant cereal. METHODS: We randomly assigned Kenyan infants (n = 191) to receive daily for 3 wk a cereal containing iron and 7.5 g GOS/FOS (7.5 g+iron group), 3 g (3-g+iron group) GOS/FOS, or no prebiotics (iron group). A subset of infants in the 2 prebiotic+iron groups (n = 66) consumed 4 stable iron isotope-labeled test meals without and with prebiotics, both before and after the intervention. Primary outcome was fractional iron absorption (FIA) from the cereal with or without prebiotics regardless of dose, before and after 3 wk of consumption. Secondary outcomes included fecal gut microbiota, iron and inflammation status, and effects of prebiotic dose. RESULTS: Median (25th-75th percentiles) FIAs from meals before intervention were as follows: 16.3% (8.0%-27.6%) without prebiotics compared with 20.5% (10.4%-33.4%) with prebiotics (Cohen d = 0.53; P < 0.001). FIA from the meal consumed without prebiotics after intervention was 22.9% (8.5%-32.4%), 41% higher than from the meal without prebiotics before intervention (Cohen d = 0.36; P = 0.002). FIA from the meal consumed with prebiotics after intervention was 26.0% (12.2%-36.1%), 60% higher than from the meal without prebiotics before intervention (Cohen d = 0.45; P = 0.007). After 3 wk, compared with the iron group, the following results were observed: 1) Lactobacillus sp. abundances were higher in both prebiotic+iron groups (P < 0.05); 2) Enterobacteriaceae sp. abundances (P = 0.022) and the sum of pathogens (P < 0.001) were lower in the 7.5-g+iron group; 3) the abundance of bacterial toxin-encoding genes was lower in the 3-g+iron group (false discovery rate < 0.05); 4) fecal pH (P < 0.001) and calprotectin (P = 0.033) were lower in the 7.5-g+iron group. CONCLUSIONS: Adding prebiotics to iron-fortified infant cereal increases iron absorption and reduces the adverse effects of iron on the gut microbiome and inflammation in Kenyan infants. This trial was registered at clinicaltrials.gov as NCT03894358.

The effects of 2'-fucosyllactose and lacto-N-neotetraose, galacto-oligosaccharides, and maternal human milk oligosaccharide profile on iron absorption in Kenyan infants.

BACKGROUND: Whether prebiotic human milk oligosaccharides (HMO), such as 2'-fucosyllactose (2'-FL) and lacto-N-neotetraose (LNnT), enhance iron absorption in infants is unknown. Moreover, whether maternal HMO profile affects absorption of iron fortificants or the effects of prebiotic galacto-oligosaccharides (GOS) and/or HMO on iron absorption is uncertain. OBJECTIVES: The aim of this study was to test whether consumption of 3.0 g GOS or HMO enhances iron absorption from iron-fortified maize porridge in partially breastfed Kenyan infants and whether maternal HMO profile modulates these effects. METHODS: In a randomized, prospective crossover study, 55 infants (aged 8-12 mo) were fed test meals fortified with 1 of the following: 1) 5.0 mg iron as 54Fe-labeled ferrous fumarate (FeFum); 2) 5.0 mg iron as 58FeFum and 3.0 g GOS (FeFum+GOS); and 3) 5.0 mg iron as 57FeFum and 2.0 g 2'-FL and 1.0 g LNnT (FeFum+HMO). Fractional iron absorption (FIA) was assessed by erythrocyte incorporation of iron isotopes. HMO profiles were determined by capillary gel electrophoresis with laser-induced florescence detection. Data were analyzed with mixed-effect models, and iron dialyzability was measured in vitro. RESULTS: Of the 55 infants included, 49 were fed as instructed. FIA from the FeFum+GOS group [median (IQR) 22.2% (16.5%-25.9%)] was higher than that from the FeFum group [12.5% (9.5%-20.9%)] (P = 0.005). FIA from the FeFum+HMO group was 13.3% (7.1%-24.4%) and did not differ from the FeFum group (P = 0.923). Maternal HMO profile did not predict FIA or modulate the effects of GOS or HMO on FIA. Iron dialyzability ratios at pH 2 of FeFum+GOS to FeFum and FeFum+HMO to FeFum were 2.1 and 0.9 (P = 0.001 and P = 0.322), respectively. CONCLUSIONS: In Kenyan infants consuming FeFum-fortified maize porridge, co-provision of 3.0 g GOS increased FIA by 78%, whereas co-provision of 3.0 g HMO did not affect FIA. Variations in maternal HMO profile, including secretor and Lewis phenotype, did not predict FIA. These data argue against a physiologic role for 2'-FL and LNnT in facilitating iron absorption in infancy. The study was registered at clinicaltrials.gov as NCT04163406 (https://clinicaltrials.gov/ct2/show/NCT04163406).

Gut microbiome function and composition in infants from rural Kenya and association with human milk oligosaccharides.

The gut microbiota evolves rapidly after birth, responding dynamically to environmental factors and playing a key role in short- and long-term health. Lifestyle and rurality have been shown to contribute to differences in the gut microbiome, including Bifidobacterium levels, between infants. We studied the composition, function and variability of the gut microbiomes of 6- to 11-month-old Kenyan infants (n = 105). Shotgun metagenomics showed Bifidobacterium longum to be the dominant species. A pangenomic analysis of B. longum in gut metagenomes revealed a high prevalence of B. longum subsp. infantis (B. infantis) in Kenyan infants (80%), and possible co-existence of this subspecies with B. longum subsp. longum. Stratification of the gut microbiome into community (GMC) types revealed differences in composition and functional features. GMC types with a higher prevalence of B. infantis and abundance of B. breve also had a lower pH and a lower abundance of genes encoding pathogenic features. An analysis of human milk oligosaccharides (HMOs) classified the human milk (HM) samples into four groups defined on the basis of secretor and Lewis polymorphisms revealed a higher prevalence of HM group III (Se+, Le-) (22%) than in most previously studied populations, with an enrichment in 2'-fucosyllactose. Our results show that the gut microbiome of partially breastfed Kenyan infants over the age of six months is enriched in bacteria from the Bifidobacterium community, including B. infantis, and that the high prevalence of a specific HM group may indicate a specific HMO-gut microbiome association. This study sheds light on gut microbiome variation in an understudied population with limited exposure to modern microbiome-altering factors.