Prebiotic galacto-oligosaccharides mitigate the adverse effects of iron fortification on the gut microbiome: a randomised controlled study in Kenyan infants

Paganini, Daniela; Uyoga, Mary A; Kortman, Guus A. M.; Cercamondi, Colin I.; Moretti, Diego; Barth‐Jaeggi, Tanja; Schwab, Clarissa; Boekhorst, Jos; Timmerman, Harro M.; Lacroix, Christophe; Karanja, Simon; Zimmermann, Michael

doi:10.1136/gutjnl-2017-314418

Cited by 145 publications

(171 citation statements)

References 37 publications

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“…A potential advantage of a lower 5-mg Fe dose with higher fractional absorption would be that w50% lower amounts of unabsorbed iron would reach the infant colon, which may lessen the chance for gut dysbiosis, inflammation, and diarrhea (4,5). Moreover, a recent intervention trial in Kenyan infants reported that the addition of GOS to an iron-containing MNP can mitigate the adverse effects of iron by enhancing the growth of bifidobacteria and lactobacilli and reducing abundances of enteropathogens (14). (27).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it is likely that the total amount of iron that was absorbed from our 5-mg dose (w0.9 mg) would be comparable to the iron that would be absorbed from MNPs containing 12.5 mg and would cover the total iron need of 0.69 mg/d in 6-12-mo-old infants (39). In a recent randomized 4-mo trial in Kenyan infants, an MNP containing 5 mg Fe as FeFum+NaFeEDTA increased hemoglobin and reduced anemia (14). A potential advantage of a lower 5-mg Fe dose with higher fractional absorption would be that w50% lower amounts of unabsorbed iron would reach the infant colon, which may lessen the chance for gut dysbiosis, inflammation, and diarrhea (4,5).…”

Section: Discussionmentioning

confidence: 99%

“…that the provision of GOSs in an iron-containing MNP mitigated the adverse effects of iron on the gut microbiome (14). Because prebiotics reduce colonic pH, they can enhance the absorption of minerals such as calcium and magnesium (12,15), and they have been proposed as potential enhancers of iron absorption.…”

Section: Introductionmentioning

confidence: 99%

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Consumption of galacto-oligosaccharides increases iron absorption from a micronutrient powder containing ferrous fumarate and sodium iron EDTA: a stable-isotope study in Kenyan infants

Paganini

Uyoga

Cercamondi

et al. 2017

The American Journal of Clinical Nutrition

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Background: Whether consumption of prebiotics increases iron absorption in infants is unclear. Objective: We set out to determine whether prebiotic consumption affects iron absorption from a micronutrient powder (MNP) containing a mixture of ferrous fumarate and sodium iron EDTA (FeFum+ NaFeEDTA) in Kenyan infants. Design: Infants (n = 50; aged 6-14 mo) consumed maize porridge that was fortified with an MNP containing FeFum+NaFeEDTA and 7.5 g galacto-oligosaccharides (GOSs) (Fe+GOS group, n = 22) or the same MNP without GOSs (Fe group, n = 28) each day for 3 wk. Then, on 2 consecutive days, we fed all infants isotopically labeled maize porridge and MNP test meals containing 5 mg Fe as 57 FeFum+Na 58FeEDTA or ferrous sulfate ( 54 FeSO 4 ). Iron absorption was measured as the erythrocyte incorporation of stable isotopes. Iron markers, fecal pH, and bacterial groups were assessed at baseline and 3 wk. Comparisons within and between groups were done with the use of mixedeffects models.Results: There was a significant group-by-compound interaction on iron absorption (P = 0.011). The median percentages of fractional iron absorption from FeFum+NaFeEDTA and from FeSO 4 in the Fe group were 11.6% (IQR: 6.9-19.9%) and 20.3% (IQR: 14.2-25.7%), respectively, (P , 0.001) and, in the Fe+GOS group, were 18.8% (IQR: 8.3-37.5%) and 25.5% (IQR: 15.1-37.8%), respectively (P = 0.124). Between groups, iron absorption was greater from the FeFum+NaFeEDTA (P = 0.047) in the Fe+GOS group but not from the FeSO 4 (P = 0.653). The relative iron bioavailability from FeFum+NaFeEDTA compared with FeSO 4 was higher in the Fe+GOS group than in the Fe group (88% compared with 63%; P = 0.006). There was a significant time-by-group interaction on Bifidobacterium spp. (P = 0.008) and Lactobacillus/Pediococcus/Leuconostoc spp. (P = 0.018); Lactobacillus/Pediococcus/Leuconostoc spp. decreased in the Fe group (P = 0.013), and there was a nonsignificant trend toward higher Bifidobacterium spp. in the Fe+GOS group (P = 0.099). At 3 wk, iron absorption was negatively correlated with fecal pH (P , 0.001) and positively correlated with Lactobacillus/Pediococcus/ Leuconostoc spp. (P = 0.001). Conclusion: GOS consumption by infants increased iron absorption by 62% from an MNP containing FeFum+NaFeEDTA, thereby possibly reflecting greater colonic iron absorption. This trial was registered at clinicaltrials.gov as NCT02666417.Am J Clin Nutr 2017;106:1020-31.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Consumption of galacto-oligosaccharides increases iron absorption from a micronutrient powder containing ferrous fumarate and sodium iron EDTA: a stable-isotope study in Kenyan infants

Paganini

Uyoga

Cercamondi

et al. 2017

The American Journal of Clinical Nutrition

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“…In the infant colon, these effects may provide a less-favorable growth environment for enteric pathogens and enhance the commensal barrier against colonization by pathogens (28,29). A recently completed intervention trial in Kenyan infants has demonstrated that addition of GOSs to an MNP containing 5 mg Fe (2.5 mg as ferrous fumarate and 2.5 mg as NaFeEDTA) effectively reduces anemia and mitigates many of the adverse effects of the iron on the gut microbiome (62).…”

Section: Strategies To Balance Need For Iron and Risk Of Adverse Effectsmentioning

confidence: 99%

The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review

Paganini

Zimmermann

2017

The American Journal of Clinical Nutrition

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In infants and young children in Sub-Saharan Africa, iron-deficiency anemia (IDA) is common, and many complementary foods are low in bioavailable iron. In-home fortification of complementary foods using iron-containing micronutrient powders (MNPs) and oral iron supplementation are both effective strategies to increase iron intakes and reduce IDA at this age. However, these interventions produce large increases in colonic iron because the absorption of their high iron dose ($12.5 mg) is typically ,20%. We reviewed studies in infants and young children on the effects of iron supplements and iron fortification with MNPs on the gut microbiome and diarrhea. Iron-containing MNPs and iron supplements can modestly increase diarrhea risk, and in vitro and in vivo studies have suggested that this occurs because increases in colonic iron adversely affect the gut microbiome in that they decrease abundances of beneficial barrier commensal gut bacteria (e.g., bifidobacteria and lactobacilli) and increase the abundance of enterobacteria including entropathogenic Escherichia coli. These changes are associated with increased gut inflammation. Therefore, safer formulations of iron-containing supplements and MNPs are needed. To improve MNP safety, the iron dose of these formulations should be reduced while maximizing absorption to retain efficacy. Also, the addition of prebiotics to MNPs is a promising approach to mitigate the adverse effects of iron on the infant gut. Am J Clin Nutr 2017;106(Suppl):1688S-93S.

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“…Considering the above, the level of iron in the gut can be manipulated to prevent the outgrowth of pathogens. For instance, the co-supplementation of iron and GOS to anaemic Kenyan infants has been shown to increase iron absorption, thereby mitigates the adverse effects of iron on the gut microbiota (Paganini et al 2017b). The abundances of Bifidobacterium and Lactobacillus spp.…”

Section: Microbiota-targeted Nutrientsmentioning

confidence: 99%

Cross-feeding interactions of gut symbionts driven by human milk oligosaccharidesand mucins

Chia¹

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Chapter 4Microbial metabolic networks at the mucus layer lead to dietindependent butyrate and vitamin B12 production by intestinal symbionts 71 Chapter 5Deciphering trophic interaction between Akkermansia muciniphila and the butyrogenic gut commensal Anaerostipes caccae using a metatranscriptomic approach 97 Chapter 6General discussion 123 Chapter 7 Thesis summary & Nederlandse samenvatting 143 Appendices References 153Co-author affiliations 179Acknowledgements 183About the author 184List of publications 185 VLAG training activities 186Chapter 1 General introduction and thesis outlineChapter 1 2 General introductionHumans can be considered holobionts, consisting of cells from the host and an even larger number of microorganisms (Postler and Ghosh 2017). The majority of microbes are residing in the gut (Sender et al 2016). The human gut microbiota is a complex ecosystem consisting of bacteria, archaea, microeukaryotes and viruses (Clemente et al 2012). Over 2000 species-level phylotypes (prokaryotes including bacteria and archaea) have been detected for the gut microbiota, with each individual estimated to host at least 160 species (Qin et al 2010, Zoetendal et al 2008. The gut microbiota may impact the well-being of human and susceptibility for diseases by interacting with our metabolic, immune and neurological system (Honda and Littman 2016, Koh et al 2016, Rogers et al 2016. Furthermore, the gut microbiota contributes to a variety of metabolic functions and can be seen as an essential part of our digestive system (El Kaoutari et al 2013). Bacterial symbionts allow the human hosts to utilise inaccessible nutrients by converting complex substrates to short chain fatty acid (SCFA) and vitamins (Fisher et al 2017). Bacterial-derived SCFAs are estimated to contribute about 10% of our daily caloric requirement (Bergman 1990). While all SCFAs are vital for maintaining gut homeostasis, butyrate is of particular interest because it has been attributed to a range of health-promoting functions. Butyrate is the primary energy source for colonic epithelial cells and is associated with the enhancement of colonic barrier function, increase of satiety, pain relief, anti-inflammatory responses, and protection against colorectal cancer (Banasiewicz et al 2013, Bolognini et al 2016, Donohoe et al 2011, Furusawa et al 2013, Goncalves and Martel 2013.Considering the physiological benefits of butyrate to human health, this thesis investigates the microbial interaction of gut symbionts that support butyrate production driven primarily by the host produced glycans in human milk and mucus. Glycans are compounds consisting of an array of glycosidically linked monosaccharides (monosaccharides and disaccharides are collectively termed sugars) such as human milk oligosaccharides (HMOS) and mucins (Varki and Kornfeld 2017). HMOS present in mother milk are the major compositional and functional driver of the infant gut microbiota (Backhed et al 2015). Mucin glycans covering the intestinal lining create a stable niche for bacterial coloni...

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Prebiotic galacto-oligosaccharides mitigate the adverse effects of iron fortification on the gut microbiome: a randomised controlled study in Kenyan infants

Cited by 145 publications

References 37 publications

Consumption of galacto-oligosaccharides increases iron absorption from a micronutrient powder containing ferrous fumarate and sodium iron EDTA: a stable-isotope study in Kenyan infants

Consumption of galacto-oligosaccharides increases iron absorption from a micronutrient powder containing ferrous fumarate and sodium iron EDTA: a stable-isotope study in Kenyan infants

The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review

Cross-feeding interactions of gut symbionts driven by human milk oligosaccharidesand mucins

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