{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T19:08:31Z","timestamp":1792955311994,"version":"4.5.0"},"reference-count":40,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2017,7,19]],"date-time":"2017-07-19T00:00:00Z","timestamp":1500422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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\u2212Fe, n = 13); or (3) Placebo (CONTROL, n = 7), from 6\u20139 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\u2212Fe (\u221216.05 \u00b1 6.9%, p = 0.05) and CONTROL (\u221219.75 \u00b1 4.5%, p = 0.01), but not in the MNP+Fe group (\u22126.23 \u00b1 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 (\u22126.38 \u00b1 2.5%, p = 0.02) and CONTROL (\u22128.05 \u00b1 1.46%, p = 0.01), but not in MNP-Fe (\u22124.27 \u00b1 5%, p = 0.4445). Clostridium increased in MNP-Fe only (1.9 \u00b1 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.<\/jats:p>","DOI":"10.3390\/nu9070776","type":"journal-article","created":{"date-parts":[[2017,7,20]],"date-time":"2017-07-20T04:28:26Z","timestamp":1500524906000},"page":"776","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Iron in Micronutrient Powder Promotes an Unfavorable Gut Microbiota in Kenyan Infants"],"prefix":"10.3390","volume":"9","author":[{"given":"Minghua","family":"Tang","sequence":"first","affiliation":[{"name":"Section of Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Frank","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Hendricks","sequence":"additional","affiliation":[{"name":"Department of Mathematical and Statistical Sciences, University of Colorado Denver, Denver, CO 80204, USA"},{"name":"Department of Biostatistics and Bioinformatics, Colorado School of Public Health, University of Colorado Denver, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Ir","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"Esamai","sequence":"additional","affiliation":[{"name":"School of Medicine, Moi University, P.O. Box 4606, Eldoret 30100, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Liechty","sequence":"additional","affiliation":[{"name":"School of Medicine, Indiana University, 705 Riley Hospital Drive, Room 5900, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Hambidge","sequence":"additional","affiliation":[{"name":"Section of Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Krebs","sequence":"additional","affiliation":[{"name":"Section of Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1182\/blood-2012-09-453522","article-title":"Control of iron deficiency anemia in low- and middle-income countries","volume":"121","author":"Pasricha","year":"2013","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"5636","DOI":"10.3390\/nu6125636","article-title":"Zinc absorption from micronutrient powder is low but is not affected by iron in Kenyan infants","volume":"6","author":"Esamai","year":"2014","journal-title":"Nutrients"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0140-6736(06)67962-2","article-title":"Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: Community-based, randomised, placebo-controlled trial","volume":"367","author":"Sazawal","year":"2006","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0140-6736(13)60437-7","article-title":"Effect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in Pakistan: A cluster-randomised trial","volume":"382","author":"Soofi","year":"2013","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Paganini, D., Uyoga, M.A., and Zimmermann, M.B. (2016). Iron Fortification of Foods for Infants and Children in Low-Income Countries: Effects on the Gut Microbiome, Gut Inflammation, and Diarrhea. Nutrients, 8.","DOI":"10.3390\/nu8080494"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0168-6445(03)00055-X","article-title":"Bacterial iron homeostasis","volume":"27","author":"Andrews","year":"2003","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/BF02013651","article-title":"Effect of iron on neonatal gut flora during the first three months of life","volume":"4","author":"Marcelis","year":"1985","journal-title":"Eur. J. Clin. Microbiol."},{"key":"ref_8","first-page":"1480","article-title":"High Iron-Sequestrating Bifidobacteria Inhibit Enteropathogen Growth and Adhesion to Intestinal Epithelial Cells In Vitro","volume":"7","author":"Werder","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.jpeds.2013.01.024","article-title":"Effects of different complementary feeding regimens on iron status and enteric microbiota in breastfed infants","volume":"163","author":"Krebs","year":"2013","journal-title":"J. Pediatr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1406","DOI":"10.3945\/ajcn.110.004564","article-title":"The effects of iron fortification on the gut microbiota in African children: A randomized controlled trial in Cote d\u2019Ivoire","volume":"92","author":"Zimmermann","year":"2010","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1136\/gutjnl-2014-307720","article-title":"Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants","volume":"64","author":"Jaeggi","year":"2015","journal-title":"Gut"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.ijgo.2012.04.022","article-title":"The Maternal and Newborn Health Registry Study of the Global Network for Women\u2019s and Children\u2019s Health Research","volume":"118","author":"Goudar","year":"2012","journal-title":"Int. J. Gynaecol. Obstet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3805","DOI":"10.4049\/jimmunol.1201257","article-title":"Prevention of Virus-Induced Type 1 Diabetes with Antibiotic Therapy","volume":"189","author":"Hara","year":"2012","journal-title":"J. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1126\/science.1233521","article-title":"Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity","volume":"339","author":"Markle","year":"2013","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6955","DOI":"10.1073\/pnas.82.20.6955","article-title":"Rapid determination of 16S ribosomal RNA sequences for phylogenetic analyses","volume":"82","author":"Lane","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1128\/jb.173.2.697-703.1991","article-title":"16S ribosomal, DNA amplification for phylogenetic study","volume":"173","author":"Weisburg","year":"1991","journal-title":"J. Bacteriol."},{"key":"ref_17","unstructured":"(2014, August 14). Homo Sapiens UCSC Hg19 Human Genome Sequence from iGenome: Illumina. Available online: http:\/\/support.illumina.com\/sequencing\/sequencing_software\/igenome.ilmn."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1101\/gr.8.3.186","article-title":"Base-calling of automated sequencer traces using phred. II. Error probabilities","volume":"8","author":"Ewing","year":"1998","journal-title":"Genome Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1101\/gr.8.3.175","article-title":"Base-calling of automated sequencer traces using phred. I. Accuracy assessment","volume":"8","author":"Ewing","year":"1998","journal-title":"Genome Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1093\/bioinformatics\/btr381","article-title":"UCHIME improves sensitivity and speed of chimera detection","volume":"27","author":"Edgar","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.1128\/AEM.02810-10","article-title":"Assessing and improving methods used in operational taxonomic unit-based approaches for 16S rRNA gene sequence analysis","volume":"77","author":"Schloss","year":"2011","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1093\/bioinformatics\/bts252","article-title":"SINA: Accurate high throughput multiple sequence alignment of ribosomal RNA genes","volume":"28","author":"Pruesse","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"D590","DOI":"10.1093\/nar\/gks1219","article-title":"The SILVA ribosomal RNA gene database project: Improved data processing and web-based tools","volume":"41","author":"Quast","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3100","DOI":"10.1093\/bioinformatics\/btt526","article-title":"Explicet: Graphical user interface software for metadata-driven management, analysis and visualization of microbiome data","volume":"29","author":"Robertson","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1017\/S0007114512001857","article-title":"Dietary folate does not significantly affect the intestinal microbiome, inflammation or tumorigenesis in azoxymethane-dextran sodium sulphate-treated mice","volume":"109","author":"MacFarlane","year":"2013","journal-title":"Br. J. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Ma, J., Sun, Q., Liu, J., Hu, Y., Liu, S., Zhang, J., Sheng, X., and Hambidge, K.M. (2016). The Effect of Iron Fortification on Iron (Fe) Status and Inflammation: A Randomized Controlled Trial. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0167458"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1097\/MPG.0000000000001154","article-title":"Effect of Vitamin E with Therapeutic Iron Supplementation on Iron Repletion and Gut Microbiome in US Iron Deficient Infants and Toddlers","volume":"63","author":"Tang","year":"2016","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"14691","DOI":"10.1073\/pnas.1005963107","article-title":"Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa","volume":"107","author":"Cavalieri","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"104","DOI":"10.3389\/fcimb.2012.00104","article-title":"The function of our microbiota: Who is out there and what do they do?","volume":"2","author":"Ottman","year":"2012","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4578","DOI":"10.1073\/pnas.1000081107","article-title":"Succession of microbial consortia in the developing infant gut microbiome","volume":"108","author":"Koenig","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1128\/AEM.02272-07","article-title":"Critical evaluation of two primers commonly used for amplification of bacterial 16S rRNA genes","volume":"74","author":"Frank","year":"2008","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1099\/mic.0.042143-0","article-title":"Determinants of the human infant intestinal microbiota after the introduction of first complementary foods in infant samples from five European centres","volume":"157","author":"Fallani","year":"2011","journal-title":"Microbiology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"E1099","DOI":"10.1210\/jc.2011-3243","article-title":"Intramyocellular lipid is associated with visceral adiposity, markers of insulin resistance, and cardiovascular risk in prepubertal children: The EPOCH study","volume":"97","author":"Brumbaugh","year":"2012","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_36","unstructured":"Kleinman, R. (2009). Iron. Pediatric Nutrition Handbook, American Academy of Pediatrics. [6th ed.]."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.3945\/jn.108.095406","article-title":"Iron deficiency in young children in low-income countries and new approaches for its prevention","volume":"138","author":"Lutter","year":"2008","journal-title":"J. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1542\/peds.2010-2576","article-title":"Diagnosis and prevention of iron deficiency and iron-deficiency anemia in infants and young children (0\u20133 years of age)","volume":"126","author":"Baker","year":"2010","journal-title":"Pediatrics"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"237","DOI":"10.3945\/jn.110.129247","article-title":"A micronutrient powder with low doses of highly absorbable iron and zinc reduces iron and zinc deficiency and improves weight-for-age Z-scores in South African children","volume":"141","author":"Troesch","year":"2011","journal-title":"J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.3945\/jn.112.157578","article-title":"Maize porridge enriched with a micronutrient powder containing low-dose iron as NaFeEDTA but not amaranth grain flour reduces anemia and iron deficiency in Kenyan preschool children","volume":"142","author":"Moretti","year":"2012","journal-title":"J. Nutr."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/7\/776\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:43:17Z","timestamp":1760208197000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/7\/776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,19]]},"references-count":40,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2017,7]]}},"alternative-id":["nu9070776"],"URL":"https:\/\/doi.org\/10.3390\/nu9070776","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,19]]}}}