Effect of Vitamin E With Therapeutic Iron Supplementation on Iron Repletion and Gut Microbiome in US Iron Deficient Infants and Toddlers

Tang, Minghua; Frank, Daniel N.; Sherlock, Laurie; Ir, Diana; Robertson, Charles E.; Krebs, Nancy F.

doi:10.1097/mpg.0000000000001154

Cited by 55 publications

(46 citation statements)

References 43 publications

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“…The four predominant phyla observed in this study were comparable to previous studies conducted by our group [ 9 , 29 ] and others [ 30 ]. However, we found a higher abundance of Proteobacteria at 38% compared with other studies [ 11 , 30 ] that reported typical abundances less than 10%.…”

Section: Discussionsupporting

confidence: 92%

Iron in Micronutrient Powder Promotes an Unfavorable Gut Microbiota in Kenyan Infants

et al. 2017

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Iron supplementation may have adverse health effects in infants, probably through manipulation of the gut microbiome. Previous research in low-resource settings have focused primarily on anemic infants. This was a double blind, randomized, controlled trial of home fortification comparing multiple micronutrient powder (MNP) with and without iron. Six-month-old, non- or mildly anemic, predominantly-breastfed Kenyan infants in a rural malaria-endemic area were randomized to consume: (1) MNP containing 12.5 mg iron (MNP+Fe, n = 13); (2) MNP containing no iron (MNP−Fe, n = 13); or (3) Placebo (CONTROL, n = 7), from 6–9 months of age. Fecal microbiota were profiled by high-throughput bacterial 16S rRNA gene sequencing. Markers of inflammation in serum and stool samples were also measured. At baseline, the most abundant phylum was Proteobacteria (37.6% of rRNA sequences). The proteobacterial genus Escherichia was the most abundant genus across all phyla (30.1% of sequences). At the end of the intervention, the relative abundance of Escherichia significantly decreased in MNP−Fe (−16.05 ± 6.9%, p = 0.05) and CONTROL (−19.75 ± 4.5%, p = 0.01), but not in the MNP+Fe group (−6.23 ± 9%, p = 0.41). The second most abundant genus at baseline was Bifidobacterium (17.3%), the relative abundance of which significantly decreased in MNP+Fe (−6.38 ± 2.5%, p = 0.02) and CONTROL (−8.05 ± 1.46%, p = 0.01), but not in MNP-Fe (−4.27 ± 5%, p = 0.4445). Clostridium increased in MNP-Fe only (1.9 ± 0.5%, p = 0.02). No significant differences were observed in inflammation markers, except for IL-8, which decreased in CONTROL. MNP fortification over three months in non- or mildly anemic Kenyan infants can potentially alter the gut microbiome. Consistent with previous research, addition of iron to the MNP may adversely affect the colonization of potential beneficial microbes and attenuate the decrease of potential pathogens.

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Section: Discussionsupporting

confidence: 92%

Iron in Micronutrient Powder Promotes an Unfavorable Gut Microbiota in Kenyan Infants

et al. 2017

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“…Furthermore, the MNP composition in Kenya contained additional micronutrients that favored beneficial gut flora. In a recent trial in US children aged 9–24 mo who were receiving therapeutic iron supplementation for iron deficiency, the addition of vitamin E to the iron supplement beneficially affected the gut microbiome, including a decrease in the relative abundance of Bacteroides and an increase in the beneficial butyrate producers Lachnospiraceae and Roseburia (31). These findings suggest that the addition of antioxidants, prebiotics, or probiotics to MNPs may overcome the proinflammatory changes in the intestine and microbiota that have been shown with iron supplementation (32–34).…”

Section: Discussionmentioning

confidence: 99%

Effects of community-based sales of micronutrient powders on morbidity episodes in preschool children in Western Kenya

Suchdev

Addo

Martorell

et al. 2016

The American Journal of Clinical Nutrition

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Background Although the use of micronutrient powders (MNPs) is considered the preferred approach for childhood anemia control, concerns about iron-related morbidity from clinical trials have challenged programmatic scale-up. Objective We aimed to measure the effects of community-based sales of MNPs on diarrhea-, fever-, cough-, and malaria-morbidity episodes in children 6–35 mo of age. Design We conducted a cluster-randomized trial in rural Western Kenya where 60 villages were randomly assigned to either intervention or control groups. MNPs (containing iron, vitamin A, zinc, and 11 other micronutrients) and other health products (e.g., insecticide-treated bednets, soap, and water disinfectant) were marketed in 30 intervention villages from June 2007 to March 2008. Household visits every 2 wk were used to monitor self-reported MNP use and morbidity (illness episodes in the previous 24 h and hospitalizations in the previous 2 wk) in both groups. Iron, vitamin A, anemia, malaria, and anthropometric measures were assessed at baseline and at 12 mo of follow-up. Data were analyzed by intent-to-treat analyses. Results Of 1062 children enrolled in the study, 1038 children (97.7%) were followed (a total of 14,204 surveillance visits). Mean MNP intake in intervention villages was 0.9 sachets/wk. Children in intervention villages, compared with children in control villages, had ~60% fewer hospitalizations for diarrhea (0.9% compared with 2.4%, respectively; P = 0.03) and 70% fewer hospitalizations for fever (1.8% compared with 5.3%, respectively; P = 0.003) but no significant differences in hospitalizations for respiratory illness (1.1% compared with 2.2%, respectively; P = 0.11) or malaria (3.1% compared with 2.9%, respectively; P = 0.82). There were no differences between groups in the numbers of episodes of diarrhea, cough, or fever. Conclusions MNP use in Western Kenya through market-based community sales was not associated with increased infectious morbidity in young children and was associated with decreased hospitalizations for diarrhea and fever. An integrated distribution of MNPs with other health interventions should be explored further in settings with a high child malnutrition and infection burden. This trial was registered at clinicaltrials.gov as NCT01088958.

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“…Given that bacteria can secrete small molecules known as siderophores that can solubilize iron for host cells (Deriu et al 2013), the opportunity is present for resident bacteria to modulate host immune responses at the mucosal interface. Iron has also been shown to modulate butyrate-producing bacteria (Tang et al 2016), as well as pathogenic Proteobacteria (Kamada et al 2013). Whether iron deficiency has a direct effect on early microbiota colonization and inflammation is a hypothesis worthy of further study.…”

Section: The Importance Of Proteobacteria To Immune Education In Earlmentioning

confidence: 99%

Maternal modifiers of the infant gut microbiota: metabolic consequences

Mulligan

Friedman

2017

Journal of Endocrinology

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Transmission of metabolic diseases from mother to child is multifactorial and includes genetic, epigenetic, and environmental influences. Evidence in rodents, humans and non-human primates support the scientific premise that exposure to maternal obesity or high-fat diet during pregnancy creates a long-lasting metabolic signature on the infant innate immune system and the juvenile microbiota which predisposes the offspring to obesity and metabolic diseases. In neonates, gastrointestinal microbes introduced through the mother are noted for their ability to serve as direct inducers/regulators of the infant immune system. Neonates have a limited capacity to initiate an immune response. Thus, disruption of microbial colonization during the early neonatal period results in disrupted postnatal immune responses that highlight the neonatal period as a critical developmental window. Although the mechanisms are poorly understood, increasing evidence suggests that maternal obesity or poor diet influences the development and modulation of the infant liver and other end-organs through direct communication via the portal system, metabolite production, alterations in gut barrier integrity, and the hematopoietic immune cell axis. This review will focus on how maternal obesity and dietary intake influence the composition of the infant gut microbiota and how an imbalance or maladaptation in the microbiota, including changes in early pioneering microbes, might contribute to the programming of offspring metabolism with special emphasis on mechanisms that promote chronic inflammation in the liver. Comprehension of these pathways and mechanisms will elucidate our understanding of developmental programming, and may expand the avenue of opportunities for novel therapeutics.

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Effect of Vitamin E With Therapeutic Iron Supplementation on Iron Repletion and Gut Microbiome in US Iron Deficient Infants and Toddlers

Cited by 55 publications

References 43 publications

Iron in Micronutrient Powder Promotes an Unfavorable Gut Microbiota in Kenyan Infants

Iron in Micronutrient Powder Promotes an Unfavorable Gut Microbiota in Kenyan Infants

Effects of community-based sales of micronutrient powders on morbidity episodes in preschool children in Western Kenya

Maternal modifiers of the infant gut microbiota: metabolic consequences

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