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.

Iron status in Swiss adolescents with paediatric major depressive disorder and healthy controls: a matched case-control study.

PURPOSE: Depression is associated with low-grade systemic inflammation and impaired intestinal function, both of which may reduce dietary iron absorption. Low iron status has been associated with depression in adults and adolescents. In Swiss adolescents, we determined the associations between paediatric major depressive disorder (pMDD), inflammation, intestinal permeability and iron status. METHODS: This is a matched case-control study in 95 adolescents with diagnosed pMDD and 95 healthy controls aged 13-17 years. We assessed depression severity using the Children's Depression Rating Scale-Revised. We measured iron status (serum ferritin (SF) and soluble transferrin receptor (sTfR)), inflammation (C-reactive protein (CRP) and alpha-1-acid-glycoprotein (AGP)), and intestinal permeability (intestinal fatty acid binding protein (I-FABP)). We assessed history of ID diagnosis and treatment with a self-reported questionnaire. RESULTS: SF concentrations did not differ between adolescents with pMDD (median (IQR) SF: 31.2 (20.2, 57.0) µg/L) and controls (32.5 (22.6, 48.3) µg/L, p = 0.4). sTfR was lower among cases than controls (4.50 (4.00, 5.50) mg/L vs 5.20 (4.75, 6.10) mg/L, p < 0.001). CRP, AGP and I-FABP were higher among cases than controls (CRP: 0.16 (0.03, 0.43) mg/L vs 0.04 (0.02, 0.30) mg/L, p = 0.003; AGP: 0.57 (0.44, 0.70) g/L vs 0.52 (0.41, 0.67) g/L, p = 0.024); I-FABP: 307 (17, 515) pg/mL vs 232 (163, 357) pg/mL, p = 0.047). Of cases, 44% reported having a history of ID diagnosis compared to 26% among controls (p = 0.020). Finally, 28% of cases had iron treatment at/close to study inclusion compared to 14% among controls. CONCLUSION: Cases had significantly higher systemic inflammation and intestinal permeability than controls but did not have lower iron status. Whether this is related to the higher rate of ID diagnosis and iron treatment in adolescents with depression is uncertain.

Another iron in C. difficile's fire.

Iron is arguably the most important nutrient in the ongoing battle between hosts and bacteria. Recently in Nature, a unique iron storage organelle, the ferrosome, was discovered in the human pathogen Clostridioides difficile.1 But what is the role of ferrosomes and how do they affect bacterial behavior and infection?

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.

Iron Absorption in Highly Trained Male Runners: Does it Matter When and Where You Eat Your Iron?

PURPOSE: We examined iron absorption and its regulation during two common scenarios experienced by endurance athletes. Our aims were to: (i) compare the effects of preexercise versus postexercise iron intake on iron absorption; and (ii) compare the impact of training at altitude (1800 m) on iron absorption preexercise. METHODS: Male runners (n = 18) completed three exercise trials over a 5-wk period, each preceded by 24 h of standardized low-iron diets. First, athletes completed two 60-min treadmill running trials at 65% V̇O2max at near sea-level (580 m). In a randomized order, preexercise and postexercise test meals labeled with 4 mg of 57Fe or 58Fe were consumed 30 min before or 30 min after exercise. Then, the same exercise trial was performed after living and training at altitude (~1800 m) for 7 d, with the labeled test meal consumed 30 min preexercise. We collected venous blood samples preexercise and postexercise for markers of iron status and regulation, and 14 d later to measure erythrocyte isotope incorporation. RESULTS: No differences in fractional iron absorption were evident when test meals were consumed preexercise (7.3% [4.4, 12.1]) or postexercise (6.2% [3.1, 12.5]) (n = 18; P = 0.058). Iron absorption preexercise was greater at altitude (18.4% [10.6, 32.0]) than at near sea-level (n = 17; P < 0.001) and hepcidin concentrations at altitude were lower at rest and 3 h postexercise compared with near sea level (P < 0.001). CONCLUSIONS: In an acute setting, preexercise and postexercise iron absorption is comparable if consumed within 30 min of exercise. Preexercise iron absorption increases 2.6-fold at altitude compared with near sea-level, likely due to the homeostatic response to provide iron for enhanced erythropoiesis and maintain iron stores.

Alternate day versus consecutive day oral iron supplementation in iron-depleted women: a randomized double-blind placebo-controlled study.

Background: Guidelines to treat iron deficiency recommend daily provision of oral iron, but this may decrease fractional iron absorption and increase side effects. Our objective was to compare consecutive-day versus alternate-day iron supplementation. Methods: In a double-masked, randomized, placebo-controlled trial, young Swiss women (n = 150; serum ferritin ≤30 µg/L) were assigned to: daily 100 mg iron for 90 d, followed by daily placebo for another 90 d (consecutive-day group) or the same daily dose of iron and placebo on alternate days for 180 d (alternate-day group). The study period was 24/11/2021-10/8/2022. Co-primary outcomes, at equal total iron doses, were serum ferritin and gastrointestinal side effects; secondary outcomes were iron deficiency and serum hepcidin. Compliance and side effects were recorded daily using a mobile application. Data were analysed using mixed models and longitudinal prevalence ratios (LPR). The trial was registered at ClinicalTrials.gov (NCT05105438). Findings: 75 women were assigned to each group and included in the intention-to-treat analysis. Capsule adherence and side effect reporting was >97% in both groups. At equal total iron doses, comparing consecutive-day and alternate-day groups, median serum ferritin was 43.8 µg/L (31.7-58.2) versus 44.8 µg/L (33.8-53.6) (P = 0.98), the LPR for gastrointestinal side effects on days of iron intake was 1.56 (95% CI: 1.38, 1.77; P < 0.0001), and median serum hepcidin was 3.0 nM (IQR 2.0-5.0) versus 1.9 nM (1.4-2.9) (P < 0.0001). Iron deficiency prevalence after 3 months was 5.5% versus 4.3% (P = 0.74) and after 6 months was 11.4% and 3.0% (P = 0.049). Interpretation: At equal total iron doses, compared to consecutive day dosing of iron, alternate day dosing did not result in higher serum ferritin but reduced iron deficiency at 6 months and triggered fewer gastrointestinal side effects. Funding: Swiss National Science Foundation, Bern, Switzerland.

The Effect of Zinc Biofortified Wheat Produced via Foliar Application on Zinc Status: A Randomized, Controlled Trial in Indian Children.

BACKGROUND: Agronomic zinc biofortification of wheat by foliar application increases wheat zinc content and total zinc absorption in humans. OBJECTIVES: To assess the effect of agronomically biofortified whole wheat flour (BFW) on plasma zinc (PZC) compared with a postharvest fortified wheat (PHFW) and unfortified control wheat (CW) when integrated in a midday school meal scheme. METHODS: We conducted a 20-wk double-blind intervention trial in children (4-12 y, n = 273) individually randomly assigned to 3 groups to receive a daily school lunch consisting of 3 chapattis prepared with the 3 different wheat flour types. Measurements of anthropometry, blood biochemistry, and leukocyte DNA strand breaks were conducted. We applied sparse serial sampling to monitor PZC over time, and analysis was performed using linear mixed-effects models. RESULTS: Mean zinc content in BFW, PHFW, and CW were 48.0, 45.1, and 21.2 ppm, respectively (P < 0.001). Mean (standard deviation) daily zinc intakes in the study intervention in BFW, PHFW, and CW groups were 4.4 (1.6), 5.9 (1.9) and 2.6 (0.6) mg Zn/d, respectively, with intake in groups PHFW and BFW differing from CW (P < 0.001) but no difference between BFW and PHFW. There were no time effect, group difference, or group × time interaction in PZC. Prevalence of zinc deficiency decreased in the BFW (from 14.1%-11.2%), PHFW (from 8.9%-2.3%), and CW (9.8%-8.8%) groups, but there was no time × treatment interaction in the prevalence of zinc deficiency (P = 0.191). Compliance with consuming the study school meals was associated with PZC (P = 0.006). DNA strand breaks were not significantly associated with PZC (n = 51; r = 0.004, P = 0.945). CONCLUSIONS: Consumption of either PHFW or BFW provided an additional ∼1.8 to 3.3 mg Zn/d, but it did not affect PZC or zinc deficiency, growth, or DNA strand breaks. This trial was registered on clinicaltrials.gov as NCT02241330 and ctri.nic.in as CTRI/2015/06/005913.

Biofortified Yellow-Fleshed Potatoes Provide More Absorbable Zinc than a Commonly Consumed Variety: A Randomized Trial Using Stable Isotopes in Women in the Peruvian Highlands.

BACKGROUND: Zinc-biofortified potatoes have considerable potential to reduce zinc deficiency because of their low levels of phytate, an inhibitor of zinc absorption, and their high consumption, especially in the Andean region of Peru. OBJECTIVES: The purpose of this study was to measure fractional and total zinc absorption from a test meal of biofortified compared with regular potatoes. METHODS: We undertook a single-blinded randomized crossover study (using 67Zn and 70Zn stable isotopes) in which 37 women consumed 500-g biofortified or regular potatoes twice a day. Urine samples were collected to determine fractional and total zinc absorption. RESULTS: The zinc content of the biofortified potato and regular potato was 0.48 (standard deviation [SD]: 0.02) and 0.32 (SD: 0.03) mg/100 g fresh weight, respectively. Mean fractional zinc absorption (FZA) from the biofortified potatoes was lower than from the regular potatoes, 20.8% (SD: 5.4%) and 25.5% (SD: 7.0%), respectively (P < 0.01). However, total zinc absorbed was significantly higher (0.49; SD: 0.13 and 0.40; SD: 0.11 mg/500 g, P < 0.01, respectively). CONCLUSIONS: The results of this study demonstrate that biofortified potatoes provide more absorbable zinc than regular potatoes. Zinc-biofortified potatoes could contribute toward reducing zinc deficiency in populations where potatoes are a staple food. This trial was registered at clinicaltrials.gov as NCT05154500.

Validation of a batch cultivation protocol for fecal microbiota of Kenyan infants.

BACKGROUND: The combination of cultivation studies with molecular analysis approaches allows characterization of the complex human gut microbiota in depth. In vitro cultivation studies of infants living in rural sub-Saharan Africa are scarce. In this study, a batch cultivation protocol for Kenyan infant fecal microbiota was validated. METHODS: Fresh fecal samples were collected from 10 infants living in a rural area of Kenya. Samples were transported under protective conditions and subsequently prepared for inoculation within less than 30 h for batch cultivation. A diet-adapted cultivation medium was used that mimicked the daily intake of human milk and maize porridge in Kenyan infants during weaning. 16 S rRNA gene amplicon sequencing and HPLC analyses were performed to assess the composition and metabolic activity, respectively, of the fecal microbiota after 24 h of batch cultivation. RESULTS: High abundance of Bifidobacterium (53.4 ± 11.1%) and high proportions of acetate (56 ± 11% of total metabolites) and lactate (24 ± 22% of total metabolites) were detected in the Kenyan infant fecal microbiota. After cultivation started at an initial pH 7.6, the fraction of top bacterial genera (≥ 1% abundant) shared between fermentation and fecal samples was high at 97 ± 5%. However, Escherichia-Shigella, Clostridium sensu stricto 1, Bacteroides and Enterococcus were enriched concomitant with decreased Bifidobacterium abundance. Decreasing the initial pH to 6.9 lead to higher abundance of Bifidobacterium after incubation and increased the compositional similarity of fermentation and fecal samples. Despite similar total metabolite production of all fecal microbiota after cultivation, inter-individual differences in metabolite profiles were apparent. CONCLUSIONS: Protected transport and batch cultivation in host and diet adapted conditions allowed regrowth of the top abundant genera and reproduction of the metabolic activity of fresh Kenyan infant fecal microbiota. The validated batch cultivation protocol can be used to study the composition and functional potential of Kenyan infant fecal microbiota in vitro.

Associations of n-3 polyunsaturated fatty acid status and intake with paediatric major depressive disorder in Swiss adolescents: A case-control study.

BACKGROUND: Observational studies suggest a link between n-3 polyunsaturated fatty acid (PUFA) intake, n-3 PUFA status, and depression in adults, but studies in adolescents are scarce. This study aimed to determine associations of n-3 PUFA status and intake with paediatric major depressive disorder (pMDD) in Swiss adolescents. METHODS: We conducted a matched case-control study in 95 adolescents diagnosed with pMDD and 95 healthy controls aged 13 to <18 years. We analysed red blood cell (RBC) fatty acid (FA) composition (% of total FA). n-3 PUFA intake was assessed using a focused food frequency questionnaire and depression severity was assessed by the Children's Depression Rating Scale-Revised (CDRS-R). RESULTS: Mean RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were lower in cases than controls (EPA: 0.41 ± 0.11 vs 0.46 ± 0.12, p < 0.001; DHA: 4.07 ± 1.04 vs 4.73 ± 1.04, p < 0.001). Subsequently, the mean RBC n-3 index was lower (4.51 ± 1.10 vs 5.20 ± 1.11, p < 0.001) and the n-6/n-3 PUFA ratio higher (5.51 ± 1.25 vs 4.96 ± 1.08, p < 0.001) in cases than controls. Adolescents with a higher n-3 index had lower odds for depression (OR = 0.49 [95% CI: 0.32-0.71]). In contrast, the n-6/n-3 PUFA ratio was associated with higher odds for depression (OR = 1.58 [95% CI: 1.14-2.25]). Intake of alpha-linolenic acid, EPA and DHA did not differ between cases and controls. CONCLUSION: Our results suggest that a higher RBC n-3 PUFA status during adolescence is associated with a lower risk for pMDD, whereas a higher n-6/n-3 PUFA ratio is associated with a higher risk for pMDD. Differences in n-3 PUFA intake did not explain the observed differences in n-3 PUFA status.

Estimating habitual iodine intake and prevalence of inadequacy from spot urine in cross-sectional studies: a modeling analysis to determine the required sample size.

BACKGROUND: The habitual/usual iodine intake and the prevalence of iodine inadequacy may be estimated from spot urinary iodine concentrations in cross-sectional studies by collecting a repeat spot urine in a subgroup of the study population and accounting for within-person variability in iodine intake. However, guidance on the required overall sample size (N) and the replicate rate (n) is lacking. OBJECTIVES: To determine the sample size (N) and replicate rate (n) needed to estimate the prevalence of iodine inadequacy in cross-sectional studies. METHODS: We used data from local observational studies conducted in women 17-49 y old in Switzerland (N = 308), South Africa (N = 154), and Tanzania (N = 190). All participants collected 2 spot urine samples. We calculated the iodine intake using urinary iodine concentrations and accounted for urine volume using urinary creatinine concentration. For each study population, we estimated the habitual iodine intake distribution and determined the prevalence of iodine intake below the average requirement using the Statistical Program to Assess habitual Dietary Exposure (SPADE). We used the obtained model parameters in power analyzes and estimated the prevalence of iodine inadequacy for different sample sizes (N = 400, 600, and 900) and replicate rates (n = 50, 100, 200, 400, 600, and 900). RESULTS: The estimated prevalence (95% CI) of inadequate iodine intake was 21% (15, 28%), 5.1% (1.3, 8.7%), and 8.2% (3.4, 13%) for Swiss, South African, and Tanzanian women, respectively. An N of 400 women, with a repeated measure (n) in 100 women, achieved a satisfactory precision of the prevalence estimate in all study populations. Increasing the replicate rate (n) improved the precision more effectively than increasing the N of the study. CONCLUSIONS: The sample size for cross-sectional studies aiming to assess the prevalence of inadequate iodine intake depend on the expected prevalence, the overall variance in intake, and the study design. However, an N of 400 participants with a repeated measure of 25% may be used as guidance when planning observational studies applying simple random sampling. This trial was registered at clinicaltrials.gov as NCT03731312.

Effect of dietary factors and time of day on iron absorption from oral iron supplements in iron deficient women.

Guidelines generally recommend taking iron supplements in the morning away from meals and with ascorbic acid (AA) to increase iron absorption. However, there is little direct evidence on the effects of dietary factors and time of day on absorption from iron supplements. In iron-depleted women (n = 34; median serum ferritin 19.4 µg/L), we administered 100 mg iron doses labeled with 54 Fe, 57 Fe, or 58 Fe in each of six different conditions with: (1) water (reference) in the morning; (2) 80 mg AA; (3) 500 mg AA; (4) coffee; (5) breakfast including coffee and orange juice (containing ~90 mg AA); and (6) water in the afternoon. Fractional iron absorption (FIA) from these n = 204 doses was calculated based on erythrocyte incorporation of multiple isotopic labels. Compared to the reference: 80 mg AA increased FIA by 30% (p < .001) but 500 mg AA did not further increase FIA (p = .226); coffee decreased FIA by 54% (p = .004); coffee with breakfast decreased FIA by 66% (p < .001) despite the presence of ~90 mg of AA. Serum hepcidin was higher (p < .001) and FIA was 37% lower (p = .059) in the afternoon compared to the morning. Our data suggest that to maximize efficacy, ferrous iron supplements should be consumed in the morning, away from meals or coffee, and with an AA-rich food or beverage. Compared to consuming a 100 mg iron dose in the morning with coffee or breakfast, consuming it with orange juice alone results in a ~ 4-fold increase in iron absorption, and provides ~20 more mg of absorbed iron per dose. The trial was registered at Clinicaltrials.gov(NCT04074707).

Total Iron Absorbed from Iron-Biofortified Potatoes Is Higher than that from Nonbiofortified Potatoes: A Randomized Trial Using Stable Iron Isotopes in Women from the Peruvian Highlands.

BACKGROUND: Yellow-fleshed potatoes biofortified with iron have been developed through conventional breeding, but the bioavailability of iron is unknown. OBJECTIVES: Our objective was to measure iron absorption from an iron-biofortified yellow-fleshed potato clone in comparison with a nonbiofortified yellow-fleshed potato variety. METHODS: We conducted a single-blinded, randomized, crossover, multiple-meal intervention study. Women (n = 28; mean ± SD plasma ferritin 21.3 ± 3.3 µg/L) consumed 10 meals (460 g) of both potatoes, each meal extrinsically labeled with either 58Fe sulfate (biofortified) or 57Fe sulfate (nonfortified), on consecutive days. Iron absorption was estimated from iron isotopic composition in erythrocytes 14 d after administration of the final meal. RESULTS: Mean ± SD iron, phytic acid, and ascorbic acid concentrations in iron-biofortified and the nonfortified potato meals (mg/per 100 mg) were 0.63 ± 0.01 and 0.31 ± 0.01, 39.34 ± 3.04 and 3.10 ± 1.72, and 7.65 ± 0.34 and 3.74 ± 0.39, respectively (P < 0.01), whereas chlorogenic acid concentrations were 15.14 ± 1.72 and 22.52 ± 3.98, respectively (P < 0.05). Geometric mean (95% CI) fractional iron absorption from the iron-biofortified clone and the nonbiofortified variety were 12.1% (10.3%-14.2%) and 16.6% (14.0%-19.6%), respectively (P < 0.001). Total iron absorption from the iron-biofortified clone and the nonbiofortified variety were 0.35 mg (0.30-0.41 mg) and 0.24 mg (0.20-0.28 mg) per 460 g meal, respectively (P < 0.001). CONCLUSIONS: TIA from iron-biofortified potato meals was 45.8% higher than that from nonbiofortified potato meals, suggesting that iron biofortification of potatoes through conventional breeding is a promising approach to improve iron intake in iron-deficient women. The study was registered at www. CLINICALTRIALS: gov as Identifier number NCT05154500.

Associations of HIV and iron status with gut microbiota composition, gut inflammation and gut integrity in South African school-age children: a two-way factorial case-control study.

BACKGROUND: Human immunodeficiency virus (HIV) and iron deficiency (ID) affect many African children. Both HIV and iron status interact with gut microbiota composition and related biomarkers. The study's aim was to determine the associations of HIV and iron status with gut microbiota composition, gut inflammation and gut integrity in South African school-age children. METHODS: In this two-way factorial case-control study, 8- to 13-year-old children were enrolled into four groups based on their HIV and iron status: (1) With HIV (HIV+) and ID (n = 43), (2) HIV+ and iron-sufficient nonanaemic (n = 41), (3) without HIV (HIV-) and ID (n = 44) and (4) HIV- and iron-sufficient nonanaemic (n = 38). HIV+ children were virally suppressed (<50 HIV RNA copies/ml) on antiretroviral therapy (ART). Microbial composition of faecal samples (16S rRNA sequencing) and markers of gut inflammation (faecal calprotectin) and gut integrity (plasma intestinal fatty acid-binding protein [I-FABP]) were assessed. RESULTS: Faecal calprotectin was higher in ID versus iron-sufficient nonanaemic children (p = 0.007). I-FABP did not significantly differ by HIV or iron status. ART-treated HIV (redundancy analysis [RDA] R2 = 0.009, p = 0.029) and age (RDA R2 = 0.013 p = 0.004) explained the variance in the gut microbiota across the four groups. Probabilistic models showed that the relative abundance of the butyrate-producing genera Anaerostipes and Anaerotruncus was lower in ID versus iron-sufficient children. Fusicatenibacter was lower in HIV+ and in ID children versus their respective counterparts. The prevalence of the inflammation-associated genus Megamonas was 42% higher in children with both HIV and ID versus HIV- and iron-sufficient nonanaemic counterparts. CONCLUSIONS: In our sample of 8- to 13-year-old virally suppressed HIV+ and HIV- children with or without ID, ID was associated with increased gut inflammation and changes in the relative abundance of specific microbiota. Moreover, in HIV+ children, ID had a cumulative effect that further shifted the gut microbiota to an unfavourable composition.

The Prevention of Iodine Deficiency: A History.

Iodine is an essential component of the hormones produced by the thyroid gland and is, therefore, essential for mammalian life. A landmark trial in the early 20th century definitively demonstrated that iodine supplementation could prevent what was then known as "endemic goiter." Subsequent studies over the next decades demonstrated that iodine deficiency causes a spectrum of disease, including not just goiter, but also cretinism, intellectual impairment, and adverse obstetric outcomes. Salt iodization, first used in Switzerland and the United States in the1920s, has become the mainstay of iodine deficiency prevention efforts. The dramatic reduction in the global prevalence of iodine deficiency disorders (IDD) over the past 30 years represents an outstanding and under-recognized public health achievement. This narrative review provides an overview of critical scientific discoveries and advances in public health nutrition related to the prevention of IDD in the United States and worldwide. This review was written to commemorate the centennial of the founding of the American Thyroid Association.

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.

Regulation of iron absorption in infants.

BACKGROUND: Iron programs in low- and middle-income countries often target infants and young children. Limited data from human infants and mouse models suggest that homeostatic control of iron absorption is incomplete in early infancy. Excess iron absorption during infancy may have detrimental effects. OBJECTIVES: Our aims were to 1) investigate determinants of iron absorption in infants aged 3-15 mo and assess whether regulation of iron absorption is fully mature during this period and 2) define the threshold ferritin and hepcidin concentrations in infancy that trigger upregulation of iron absorption. METHODS: We performed a pooled analysis of standardized, stable iron isotope absorption studies performed by our laboratory in infants and toddlers. We used generalized additive mixed modeling (GAMM) to examine relationships between ferritin, hepcidin, and fractional iron absorption (FIA). RESULTS: Kenyan and Thai infants aged 2.9-15.1 mo (n = 269) were included; 66.8% were iron deficient and 50.4% were anemic. In regression models, hepcidin, ferritin, and serum transferrin receptor were significant predictors of FIA, whereas C-reactive protein was not. In the model including hepcidin, hepcidin was the strongest predictor of FIA (ß = -0.435). In all models, interaction terms, including age, were not significant predictors of FIA or hepcidin. The fitted GAMM trend of ferritin versus FIA showed a significant negative slope until ferritin of 46.3 µg/L (95% CI: 42.1, 50.5 µg/L), which corresponded to an FIA decrease from 26.5% to 8.3%; above this ferritin value, FIA remained stable. The fitted GAMM trend of hepcidin versus FIA showed a significant negative slope until hepcidin of 3.15 nmol/L (95% CI: 2.67, 3.63 nmol/L), above which FIA remained stable. CONCLUSIONS: Our findings suggest that the regulatory pathways of iron absorption are intact in infancy. In infants, iron absorption begins to increase at threshold ferritin and hepcidin values of ∼46 µg/L and ∼3 nmol/L, respectively, similar to adult values.

The remarkable impact of iodisation programmes on global public health.

The objective of this paper is to review the global effort to eliminate iodine deficiency and its impact on public health. Iodine is an essential component of hormones produced by the thyroid gland. Iodine deficiency has multiple adverse effects in humans due to inadequate thyroid hormone production that are termed the iodine deficiency disorders. The major adverse effect is impaired cognition in children. The WHO's first estimate of the global prevalence of goitre in 1960 suggested that 20-60 % of the world's population was affected, with most of the burden in low- and middle-income countries. Iodine deficiency was identified as a key global risk factor for impaired child development where the need for intervention was urgent. This spurred a worldwide effort to eliminate iodine deficiency led by a coalition of international organisations working closely with national governments and the salt industry. In most countries, the best strategy to control iodine deficiency is carefully monitored iodisation of salt. The reach of current iodised salt programmes is remarkable: in 2018, 88 % of the global population used iodised salt. The number of countries with adequate iodine intake has nearly doubled over the past 20 years from 67 in 2003 to 118 in 2020. The resulting improvement in cognitive development and future earnings suggests a potential global economic benefit of nearly $33 billion. Iodine programmes are appealing for national governments because the health and economic consequences are high and can be easily averted by salt iodisation, a low-cost and sustainable intervention.

The effect of dechitinization on iron absorption from mealworm larvae (Tenebrio molitor) flour added to maize meals: stable-isotope studies in young females with low iron stores.

BACKGROUND: Edible insects have a low ecological footprint and could serve as an alternative dietary iron source. However, chitin, a major component of insects, avidly binds iron and might inhibit iron absorption. OBJECTIVES: We aimed to measure fractional iron absorption (FIA) from Tenebrio molitor-based test meals with and without dechitinization, and to assess the effect of native and low chitin T. molitor on FIA from iron-fortified maize porridge. METHODS: We measured iron absorption in young females with low iron stores (n = 21) from 1) labeled (54FeSO4) fortified maize porridge (maize alone); 2) intrinsically labeled (57Fe added during rearing) T. molitor larvae with native chitin content (NC) added to maize alone; and 3) dechitinized intrinsically labeled (57Fe) T. molitor larvae with low chitin content (LC) added to maize alone. We determined FIA using erythrocyte isotope incorporation and measured in vitro iron dialyzability from the 3 meals. RESULTS: NC and LC T. molitor had similar mean ± SD iron content (12.0 ± 0.1 mg/100 g). Geometric mean (95% CI) FIAs from the 3 test meals were 1) maize alone: 5.8% (3.2%, 10.8%); 2) maize + NC T. molitor: 5.3% (2.5%, 11.3%) and 4.1% (1.9%, 8.7%); and 3) maize + LC T. molitor: 4.6% (2.0%, 10.3%) and 4.0% (1.8%, 9.2%), for extrinsic and intrinsic labels, respectively. FIA from NC and LC T. molitor did not significantly differ, and both were lower (P < 0.005) than FIA from the labeled maize porridge in the 3 meals, which did not significantly differ. The slopes of the relations between FIA and serum ferritin in the different meals and from the intrinsic and extrinsic labels did not significantly differ. CONCLUSIONS: T. molitor biomass does not strongly affect iron absorption when added to maize porridge. Our data suggest T. molitor iron is absorbed from the common nonheme iron pool. Native T. molitor is high in iron which is moderately well absorbed, suggesting it could be a valuable dietary iron source.This trial was registered at clinicaltrials.gov as NCT04510831.