Sight and Life Magazine 1/2011

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52 IRON FORTIFICATION – NEW REVELATIONS?disease which was reported in 2004 to affect 1.4 million peoplein the United States, and 2.2 million in Europe. 39T reg cells are also derived from CD4 + T cells. Their importancelies in their ability to suppress the immune responses of othercells – that is, to keep the immune responses in check. The authorsshowed that the increase in Treg in response to oral inoculationwith Clostridia (spp) during the early life of conventionallyreared mice promoted anti-inflammatory immune responsesand were more resistant to experimental models of allergy andexperimental colitis – the murine equivalent of IBD. The paperis a fascinating piece of investigative murine microbiology but,unfortunately, there is not space to discuss it in detail. Interestingly,the ability to stimulate T regs was not blocked by SFBbacteria or Lactobacilli. A cocktail of 45 strains of Clostridia wasmore effective in raising T reg production than three strains indicating,possibly, that a number of stimuli is necessary for a fullresponse. 5 Clostridium species appear to be specialized in theirability to promote T reg cell accumulation in the colon. 25 Adherenceto the intestinal epithelium did not appear to be necessary,as in the case of SFB bacteria, possibly because Clostridia spppromoted the release of the transforming growth factor- thatstimulated CD4 + T cell differentiation. 25 The effects of these bacteriaon T-cell development give us a clear indication that, potentially,many fecal bacteria may have an important influenceon immune defenses in the gut and on the systemic health of thehost. We currently have little idea of the specific role of iron inthis “orchestra.”Concluding remarksThree papers have been discussed in this report, which describesinteractions between diet, the microbiota and the immune system.The paper by the Zimmermann group illustrates that anincrease in a poorly available form of iron was associated withalterations in the colonic microbiota and evidence of inflammationin the intestinal lining. 3 The two other papers illustrate thatspecific, or groups of, gram-positive bacteria can have stimulatoryeffects on the immune system and promote potentiallyinflammatory 4 and anti-inflammatory 5 immune responses. Theiron supplementation study identified an increase in the gramnegative,enterobacterial fecal fraction as being positively associatedwith calprotectin, a biomarker of inflammation. Therewere also increases in several species of pathogenic bacteria inthis group and some were identified in several of the children. Inaddition, there was a reduction in the gram-positive Lactobacillusgroup of bacteria.Host protection against bacterial pathogenicity is partly affordedby the large number of commensal bacteria in the microbiota,many of which will occupy important niches within theintestinal lining and so prevent occupancy by incoming pathogenicstrains. 40 Dietary requirements will also determine whichbacteria can propagate themselves at the expense of others. Ironis an important regulator of bacterial growth and pathogenicity.Supplemental iron may well have been responsible for the fourfoldincrease in the numbers of enterobacteria and the associatedinflammation. The particular bacterial species and mechanismcausing the inflammation are not known, but the markedeffects that SFB bacteria and Clostridia spp can have on T-cellregulation indicate the type of mechanism that may have beeninvolved. As the authors suggest, minimizing the inflammatoryeffects of supplemental iron may be possible with a lower doseof more bioavailable iron to promote iron uptake and reduce theamount available to the microbiota.In the last issue of Sight and Life, Barbara Troesch, from thesame group, reported on the successful use of low-dose ironfrom NaFeEDTA, in combination with ascorbic acid and phytase,to increase body iron stores and reduce iron and zinc deficiencyin South African school children. 41 It should also be rememberedthat the study in Côte d’Ivoire was intended to show the potentialeffects of food fortified with iron. In fact, the iron load was18.2 mg/day, given in a biscuit four days/week. The equivalentdaily dose of fortified iron would have been 8.8 mg iron/day, butthis amount may not have had the same microbiological or inflammatoryeffects as the higher dose. Currently, the selection ofthe type and quantity of vitamins and minerals to add to flour,either as a voluntary standard or a mandatory requirement, lieswith national decision-makers in each country. As a result, thechoice of compounds as well as quantities should be viewed inthe context of each country’s situation. Recommended amountsof electrolytic iron are only given where the daily consumptionof flour is >150 g (60 ppm) or >300 g (40 ppm) for low extractionflour or 20 and 15 ppm resp. for those amounts of high extractionflour. 42 Three hundred grams of flour containing 40 ppm Fe isequivalent to a daily intake of 18 mg iron, i.e. comparable to theamount used in the Ivorian children. Thus, the effects of the ironsupplement reported by Zimmermann and colleagues 3 are applicableto those countries where flour is fortified with electrolyticiron, and there is a high consumption of wheat flour.Correspondence: David I Thurnham, 46 High Street,Little Wilbraham, Cambridge CB21 5JY, United KingdomE-mail: di.thurnham@ulster.ac.uk
SIGHT AND LIFE | VOL. 25 (1) | 2011 IRON FORTIFICATION – NEW REVELATIONS? 5353References01. Sazawal S, Black RE, Ramsan M et al. Effects of routine prophylacticsupplementation with iron and folic acid on admission to hospitaland mortality in preschool children in a high malaria transmissionsetting: community-based, randomised, placebo-controlled trial.Lancet 2006;367:133-143.02. Suchdev PS, Leeds IL, McFarland DA et al. Is it time to change theguidelines for iron supplementation in malarial areas?J Nutr 2010;140:875-876.03. Zimmermann MB, Chassard C, Rohner F et al. The effects of ironfortification on the gut microbiota in African children: a randomizedcontrolled trial in Cote d'Ivoire. Am J Clin Nutr 2010;92:1406-1415.04. Ivanov II, Littman DR. Segmented filamentous bacteria take thestage. Mucosal Immunol 2010;3:209-212.05. Atarashi K, Tanoue T, Shima T et al. Induction of ColonicRegulatory T Cells by Indigenous Clostridium Species. Science2011;331:337-341.06. World Health Organization. Iron deficiency anaemia: assessment,prevention and control. A guide for programme managers. WHO/NHD/01.3. 2001. Geneva, World Health Organisation.07. Guidelines on food fortification with micronutrients. Geneva: WorldHealth Organisation & Food and Agricultural Organisation; 2006.08. Haas JD, Brownlie T4. Iron deficiency and reduced work capacity:a critical review of the research to determine a causal relationship.J Nutr 2001;131:676S-690S.09. Pollitt E. The developmental and probabilistic nature of the functionalconsequences of iron-deficiency anemia in children. J Nutr2001;131:669S-675S.10. Stoltzfus RJ. Iron-deficiency anemia: reexamining the nature andmagnitude of the public health problem. Summary: implications forresearch and programs. J Nutr 2001;131:697S-700S.11. McFarlane H, Reddy S, Adcock KJ et al. Immunity, transferrin andsurvival in kwashiorkor. B M J 1970;4:268-270.12. United States Food and Drug Administration. US FDA Backgrounder.Preventing iron poisoning in children. 62 FR 2217. 1997.13. Chua AC, Klopcic B, Lawrance IC et al. Iron: an emerging factor incolorectal carcinogenesis. World J Gastroenterol 2010;16:663-672.14. Bastide NM, Pierre FH, Corpet D. Heme iron from meat and risk ofcolorectal cancer: a meta-analysis and a review of the mechanismsinvolved. Cancer Prev Res (Phila) 2011; Jan 5 ahead of print.15. Baltussen R, Knai C, Sharan M. Iron fortification and iron supplementationare cost-effective interventions to reduce iron deficiencyin four subregions of the world. J Nutr 2004; 134:2678-2684.16. Zimmermann MB, Hurrell RF. Nutritional iron deficiency. Lancet2007; 370:511-520.17. Andrews SC, Robinson AK, Rodríguez-Quiñones F. Bacterial ironhomeostasis. FEMS Microbiol Rev 2003;27:215-237.18. Naikare H, Palyada K, Panciera R et al. Major role for FeoBin Campylobacter jejuni iron acquisition, gut colonization andintracellular survival. Infect Immun 2006; 74:5433-5444.19. Lee SH, Shine P, Choi J et al. Effects of dietary iron levels on growthperformance, hematological status, liver mineral concentration,fecal microflora, and diarrhea incidence in weanling pigs. Biol TraceElement Res 2008;126:S57-S68.20. World Health Organisation. Conclusions and recommendations ofthe WHO consultation on prevention and control of iron deficiencyin infants and young children in malaria-endemic areas. Food NutrBull 2007;28:S621-S627.21. Rohner F, Zimmermann MB, Amon RJ et al. In a randomizedcontrolled trial of iron fortification, anthelmintic treatment, andintermittent preventive treatment of malaria for anemia control inIvorian children, only anthelmintic treatment shows modestbenefit. J Nutr 2010;140:635-641.22. Thurnham DI, McCabe GP, Northrop-Clewes CA et al. Effect ofsubclinical infection on plasma retinol concentrations and assessmentof prevalence of vitamin A deficiency: meta-analysis. Lancet2003;362:2052-2058.23. Thurnham DI, McCabe LD, Haldar S et al. Adjusting plasma ferritinconcentrations to remove the effects of subclinical inflammation inthe assessment of iron deficiency: a meta-analysis. Am J Clin Nutr2010; 92:546-555.24. Monira S, Alam NH, Suau A et al. Time course of bacterial diversityin stool samples of malnourished children with cholera receivingtreatment. J Pediatr Gastroenterol Nutr 2009;48:571-578.25. Barnes MJ, Powrie F. The gut's Clostridium cocktail. Science2011;331:289-291.26. Gisbert JP, McNicholl AG. Questions and answers on the role offaecal calprotectin as a biological marker in inflammatory boweldisease. Dig Liver Dis 2009;41:56-66.27. Fagerberg UL, Lööf L, Merzoug RD et al. Fecal calprotectin levels inhealthy children studied with an improved assay. J Pediatr GastroenterolNutr 2003;37:472468.28. Angriman I, Scarpa M, D'Incà R et al. Enzymes in feces: useful markersof chronic inflammatory bowel disease. Clin Chim Acta 2007;381:63-68.29. Tøn H, Brandsnes, Dale S et al. Improved assay for fecal calprotectin.Clin Chim Acta 2000; 292:41-54.30. Hopkins MJ, Sharp R, Macfarlane GT. Age and disease relatedchanges in intestinal bacterial populations assessed by cell culture,16S rRNA abundance, and community cellular fatty acid profiles.Gut 2001;48:198-205.⇢
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Page 8 and 9: 8EDITORIALOur history between two c
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Page 16 and 17: 16THE IMPORTANCE OF VITAMIN AThe Im
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Page 44 and 45: 44IRON FORTIFICATION - NEW REVELATI
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Page 56 and 57: 56 OPINION 1 / 2depending upon spec
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Page 96 and 97: 96Comments on the Comparison of the
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Page 100 and 101: 100 PUBLICATIONSOmega-3Fatty Acids
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Sharingknowledgefor improvednutriti
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