Gut microbiome signatures associated with iron-deficiency anemia in young adults
,
Abstract
Background and Objectives: Iron is vital for both the body of the host and the metabolism of microbes. Pathogenic Enterobacteria need iron to grow and cause disease, but many good gut bacteria, like lactobacilli, do not require as much iron. Changes in the amount of iron available in the gut may therefore affect the makeup of the gut microbiome. Iron-deficiency anemia (IDA) represents the most prevalent nutritional disorder globally, concerning about 1.24 billion, mostly women and young people in low- and middle-income countries. This cross-sectional study looked at the link between iron-deficiency anemia and the makeup of the gut microbiome in young adults aged 18 to 30.
Materials and Methods: We looked at hematological and iron status parameters as well as gut microbiota profiling using 16S rRNA gene sequencing. Differences in microbial diversity, taxonomic composition, and the relative abundance of bacteria that make short-chain fatty acids between people with IDA and healthy controls were investigated.
Results: The results show that iron-deficiency anemia is linked to different gut microbiome signatures. This suggests that there may be connections between iron levels and the structure of microbial communities.
Conclusion: These results show how important it is to study the gut microbiome to understand iron-deficiency anemia. They also show how important it is to do long-term, interventional studies to figure out how these associations work and what they mean for health.
1. Camaschella C. Iron-deficiency anemia. N Engl J Med 2015;372:1832-1843.
2. Ganz T. Anemia of inflammation and iron metabolism. N Engl J Med 2019;381:1148-1157.
3. Pasricha SR, Gheorghe A, Sakr-Ashour F, Arcot A, Neufeld L, Murray-Kolb LE, et al. Net benefit and cost-effectiveness of universal iron-containing multiple micronutrient powders for young children in 78 countries: a microsimulation study. Lancet Glob Health 2020;8(8):e1071-e1080.
4. Finlayson-Trick E, Montes K, Cheema M, Osman M. Methodological considerations for stool sample collection in microbiome research. Microbiome Res Rep 2020;8:112-121.
5. Paganini D, Uyoga MA, Zimmermann MB. Iron fortification of foods for infants and children in low-income countries: effects on the gut microbiome, gut inflammation, and diarrhea. Nutrients 2016;8:494.
6. Jaeggi T, Kortman G, Moretti D, Chassard C, Holding PA, Dostal A, et al. Iron fortification and its effects on gut microbiota in young adults. Gut Microbes 2015;6:180-192.
7. Tang M, Frank DN, Hendricks AE, Ir D, Esamai F, Liechty E, et al. Iron in micronutrient powder promotes an unfavorable gut microbiota in Kenyan infants. Nutrients 2017;9:776.
8. Lee T, Clavel T, Smirnov K, Schmidt A, Lagkouvardos I, Walker AW, et al. Gut microbiome signatures in gastrointestinal diseases. Nat Rev Gastroenterol Hepatol 2017;14:509-526.
9. Cook JD, Reddy MB. Efficacy of weekly compared with daily iron supplementation. Am J Clin Nutr 1995;62:117-120.
10. Wang CY, Babitt JL. Liver iron sensing and body iron homeostasis. Blood 2019;133:18-29.
11. Anderson GJ, Vulpe CD. Mammalian iron transport. Cell Mol Life Sci 2009;66:3241-3261.
12. Jimenez KM, Gasche C. Management of iron deficiency anaemia in inflammatory bowel disease. Acta Haematol 2019;142:30-36.
13. Kramer J, Özkaya Ö, Kümmerli R. Bacterial siderophores in community and host interactions. Nat Rev Microbiol 2020;18:152-163.
14. Lopez A, Cacoub P. Iron deficiency and anemia in clinical practice. J Intern Med 2016;281:566-578.
15. Pasricha SR, Tye-Din J, Muckenthaler MU, Swinkels DW. Iron deficiency. Lancet 2021;397:233-248.
16. Cantor AG, Holmes R, Bougatsos C, Atchison C, DeLoughery T, Chou R. Screening and supplementation for iron deficiency and iron deficiency anemia during pregnancy: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2024;332:914-928.
17. The Lancet Haematology. Iron deficiency anaemia—an ongoing challenge. Lancet Haematol 2022;9(11):e797.
18. Mayneris-Perxachs J, Moreno-Navarrete JM, Fernandez-Real JM. The role of iron in host-microbiota crosstalk and its effects on systemic glucose metabolism. Nat Rev Endocrinol 2022;18:683-698.
19. Phipps O, Al-Hassi HO, Quraishi MN, Kumar A, Brookes MJ. Influence of iron on the gut microbiota in colorectal cancer. Nutrients 2020;12:2512.
20. Sun B, Tan B, Zhang P, Zhu L, Wei H, Huang T, et al. Iron deficiency anemia: a critical review on iron absorption, supplementation and its influence on gut microbiota. Food Funct 2024;15:1144-1157.
21. Muleviciene A, D’Amico F, Turroni S, Candela M, Jankauskiene A. Iron deficiency anemia-related gut microbiota dysbiosis in infants and young children: a pilot study. Acta Microbiol Immunol Hung 2018;65:551-564.
22. Kortman GA, Raffatellu M, Swinkels DW, Tjalsma H. Nutritional iron turned inside out: intestinal stress from a microbial perspective. FEMS Microbiol Rev 2014;38:1202-1234.
23. World Health Organization. Anaemia in women and children. Geneva: WHO; 2023. https://www.who.int/news-room/fact-sheets/detail/anaemia
24. Wirth JP, Woodruff BA, Engle-Stone R, Namaste SM, Temple VJ, Petry N, et al. Predictors of anemia in women of reproductive age: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr 2017;106(Suppl 6):416S-427S.
25. Engle-Stone R, Aaron GJ, Huang J, Wirth JP, Namaste SM, Williams AM, et al. Predictors of anemia in preschool children: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr 2017;106(Suppl 6):402S-415S.
26. Miller JL. Iron deficiency anemia: a common and curable disease. Cold Spring Harb Perspect Med 2013;3(7):a011866.
27. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017;390:1211-1259.
28. Prentice AM, Mendoza YA, Pereira D, Cerami C, Wegmuller R, Constable A, et al. Dietary strategies for improving iron status: balancing safety and efficacy. Nutr Rev 2017;75:49-60.
29. Grantham-McGregor S, Ani C. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 2001;131(2S-2):649S-666S.
30. Halterman JS, Kaczorowski JM, Aligne CA, Auinger P, Szilagyi PG. Iron deficiency and cognitive achievement among school-aged children and adolescents in the United States. Pediatrics 2001;107:1381-1386.
31. Horton S, Ross J. The economics of iron deficiency. Food Policy 2003;28:51-75.
32. World Health Organization. Guideline: Daily iron supplementation in infants and children. Geneva: WHO;2016. https://www.who.int/publications/i/item/9789241549523
33. Soofi S, Cousens S, Iqbal SP, Akhund T, Khan J, Ahmed I, et al. Effect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in Pakistan: a cluster-randomised trial. Lancet 2013;382:29-40.
34. Prentice AM. Iron metabolism, malaria, and other infections: what is all the fuss about? J Nutr 2008;138:2537-2541.
35. Mayo-Wilson E, Imdad A, Junior J, Dean S, Bhutta ZA. Preventive zinc supplementation for children, and the effect of additional iron: a systematic review and meta-analysis. BMJ Open 2014;4(6):e004647.
36. Zimmermann MB, Chassard C, Rohner F, N'goran EK, Nindjin C, Dostal A, et al. The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d'Ivoire. Am J Clin Nutr 2010;92:1406-1415.
37. Suchdev PS, Jefferds ME, Ota E, da Silva Lopes K, De-Regil LM. Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age. Cochrane Database Syst Rev 2020;2(2):CD008959.
38. Lee T, Clavel T, Smirnov K, Schmidt A, Lagkouvardos I, Walker A, et al. Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD. Gut 2017;66:863-871.
39. Mwangi MN, Phiri KS, Abkari A, Gbané M, Bourdet-Sicard R, Braesco VA, et al. Iron for Africa—Report of an Expert Workshop. Nutrients 2017;9:576.
40. Tang M, Frank DN, Hendricks B. Supplemental iron alters the gut microbiota and increases pathogenic bacterial growth. J Nutr 2017;147:2230-2239.
41. Cantor AG, Bougatsos C, Dana T, Blazina I, McDonagh M, Daugird A. Screening and supplementation strategies for iron deficiency anemia: updated clinical guidelines. J Clin Hematol 2024;12:45-62.
42. Finlayson-Trick ECL, Fischer JAJ, Goldfarb DM, Karakochuk CD. The effects of iron supplementation and fortification on the gut microbiota: a review. Gastrointest Disord 2020;2:327-340.
43. Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods 2016;13:581-583.
44. Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet CC, Al-Ghalith GA, et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol 2019;37:852-857.
45. Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, et al. Metagenomic biomarker discovery and explanation. Genome Biol 2011;12(6):R60.
46. Fritz CO, Morris PE, Richler JJ. Effect size estimates: Current use, calculations, and interpretation. J Exp Psychol Gen 2012;141:2-18.
47. Anderson MJ. Permutational multivariate analysis of variance (PERMANOVA). Wiley StatsRef: Statistics Reference Online 2017:1-15.
48. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Methodol 1995;57:289-300.
49. Zimmermann MB, Hurrell RF. Iron deficiency and the gut microbiome. Annu Rev Nutr 2017;37:131-157.
50. Dostal A, Chassard C, Hilty FM, Zimmermann MB, Lacroix C. Iron depletion modifies gut microbiota composition. J Nutr 2015;145:1312-1320.
51. Kortman GAM, Raffatellu M, Swinkels DW, Tjalsma H. Interactions between iron metabolism and the gut microbiome. Nat Rev Gastroenterol Hepatol 2014;11:411-423.
2. Ganz T. Anemia of inflammation and iron metabolism. N Engl J Med 2019;381:1148-1157.
3. Pasricha SR, Gheorghe A, Sakr-Ashour F, Arcot A, Neufeld L, Murray-Kolb LE, et al. Net benefit and cost-effectiveness of universal iron-containing multiple micronutrient powders for young children in 78 countries: a microsimulation study. Lancet Glob Health 2020;8(8):e1071-e1080.
4. Finlayson-Trick E, Montes K, Cheema M, Osman M. Methodological considerations for stool sample collection in microbiome research. Microbiome Res Rep 2020;8:112-121.
5. Paganini D, Uyoga MA, Zimmermann MB. Iron fortification of foods for infants and children in low-income countries: effects on the gut microbiome, gut inflammation, and diarrhea. Nutrients 2016;8:494.
6. Jaeggi T, Kortman G, Moretti D, Chassard C, Holding PA, Dostal A, et al. Iron fortification and its effects on gut microbiota in young adults. Gut Microbes 2015;6:180-192.
7. Tang M, Frank DN, Hendricks AE, Ir D, Esamai F, Liechty E, et al. Iron in micronutrient powder promotes an unfavorable gut microbiota in Kenyan infants. Nutrients 2017;9:776.
8. Lee T, Clavel T, Smirnov K, Schmidt A, Lagkouvardos I, Walker AW, et al. Gut microbiome signatures in gastrointestinal diseases. Nat Rev Gastroenterol Hepatol 2017;14:509-526.
9. Cook JD, Reddy MB. Efficacy of weekly compared with daily iron supplementation. Am J Clin Nutr 1995;62:117-120.
10. Wang CY, Babitt JL. Liver iron sensing and body iron homeostasis. Blood 2019;133:18-29.
11. Anderson GJ, Vulpe CD. Mammalian iron transport. Cell Mol Life Sci 2009;66:3241-3261.
12. Jimenez KM, Gasche C. Management of iron deficiency anaemia in inflammatory bowel disease. Acta Haematol 2019;142:30-36.
13. Kramer J, Özkaya Ö, Kümmerli R. Bacterial siderophores in community and host interactions. Nat Rev Microbiol 2020;18:152-163.
14. Lopez A, Cacoub P. Iron deficiency and anemia in clinical practice. J Intern Med 2016;281:566-578.
15. Pasricha SR, Tye-Din J, Muckenthaler MU, Swinkels DW. Iron deficiency. Lancet 2021;397:233-248.
16. Cantor AG, Holmes R, Bougatsos C, Atchison C, DeLoughery T, Chou R. Screening and supplementation for iron deficiency and iron deficiency anemia during pregnancy: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA 2024;332:914-928.
17. The Lancet Haematology. Iron deficiency anaemia—an ongoing challenge. Lancet Haematol 2022;9(11):e797.
18. Mayneris-Perxachs J, Moreno-Navarrete JM, Fernandez-Real JM. The role of iron in host-microbiota crosstalk and its effects on systemic glucose metabolism. Nat Rev Endocrinol 2022;18:683-698.
19. Phipps O, Al-Hassi HO, Quraishi MN, Kumar A, Brookes MJ. Influence of iron on the gut microbiota in colorectal cancer. Nutrients 2020;12:2512.
20. Sun B, Tan B, Zhang P, Zhu L, Wei H, Huang T, et al. Iron deficiency anemia: a critical review on iron absorption, supplementation and its influence on gut microbiota. Food Funct 2024;15:1144-1157.
21. Muleviciene A, D’Amico F, Turroni S, Candela M, Jankauskiene A. Iron deficiency anemia-related gut microbiota dysbiosis in infants and young children: a pilot study. Acta Microbiol Immunol Hung 2018;65:551-564.
22. Kortman GA, Raffatellu M, Swinkels DW, Tjalsma H. Nutritional iron turned inside out: intestinal stress from a microbial perspective. FEMS Microbiol Rev 2014;38:1202-1234.
23. World Health Organization. Anaemia in women and children. Geneva: WHO; 2023. https://www.who.int/news-room/fact-sheets/detail/anaemia
24. Wirth JP, Woodruff BA, Engle-Stone R, Namaste SM, Temple VJ, Petry N, et al. Predictors of anemia in women of reproductive age: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr 2017;106(Suppl 6):416S-427S.
25. Engle-Stone R, Aaron GJ, Huang J, Wirth JP, Namaste SM, Williams AM, et al. Predictors of anemia in preschool children: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Am J Clin Nutr 2017;106(Suppl 6):402S-415S.
26. Miller JL. Iron deficiency anemia: a common and curable disease. Cold Spring Harb Perspect Med 2013;3(7):a011866.
27. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017;390:1211-1259.
28. Prentice AM, Mendoza YA, Pereira D, Cerami C, Wegmuller R, Constable A, et al. Dietary strategies for improving iron status: balancing safety and efficacy. Nutr Rev 2017;75:49-60.
29. Grantham-McGregor S, Ani C. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 2001;131(2S-2):649S-666S.
30. Halterman JS, Kaczorowski JM, Aligne CA, Auinger P, Szilagyi PG. Iron deficiency and cognitive achievement among school-aged children and adolescents in the United States. Pediatrics 2001;107:1381-1386.
31. Horton S, Ross J. The economics of iron deficiency. Food Policy 2003;28:51-75.
32. World Health Organization. Guideline: Daily iron supplementation in infants and children. Geneva: WHO;2016. https://www.who.int/publications/i/item/9789241549523
33. Soofi S, Cousens S, Iqbal SP, Akhund T, Khan J, Ahmed I, et al. Effect of provision of daily zinc and iron with several micronutrients on growth and morbidity among young children in Pakistan: a cluster-randomised trial. Lancet 2013;382:29-40.
34. Prentice AM. Iron metabolism, malaria, and other infections: what is all the fuss about? J Nutr 2008;138:2537-2541.
35. Mayo-Wilson E, Imdad A, Junior J, Dean S, Bhutta ZA. Preventive zinc supplementation for children, and the effect of additional iron: a systematic review and meta-analysis. BMJ Open 2014;4(6):e004647.
36. Zimmermann MB, Chassard C, Rohner F, N'goran EK, Nindjin C, Dostal A, et al. The effects of iron fortification on the gut microbiota in African children: a randomized controlled trial in Cote d'Ivoire. Am J Clin Nutr 2010;92:1406-1415.
37. Suchdev PS, Jefferds ME, Ota E, da Silva Lopes K, De-Regil LM. Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age. Cochrane Database Syst Rev 2020;2(2):CD008959.
38. Lee T, Clavel T, Smirnov K, Schmidt A, Lagkouvardos I, Walker A, et al. Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD. Gut 2017;66:863-871.
39. Mwangi MN, Phiri KS, Abkari A, Gbané M, Bourdet-Sicard R, Braesco VA, et al. Iron for Africa—Report of an Expert Workshop. Nutrients 2017;9:576.
40. Tang M, Frank DN, Hendricks B. Supplemental iron alters the gut microbiota and increases pathogenic bacterial growth. J Nutr 2017;147:2230-2239.
41. Cantor AG, Bougatsos C, Dana T, Blazina I, McDonagh M, Daugird A. Screening and supplementation strategies for iron deficiency anemia: updated clinical guidelines. J Clin Hematol 2024;12:45-62.
42. Finlayson-Trick ECL, Fischer JAJ, Goldfarb DM, Karakochuk CD. The effects of iron supplementation and fortification on the gut microbiota: a review. Gastrointest Disord 2020;2:327-340.
43. Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJA, Holmes SP. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods 2016;13:581-583.
44. Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet CC, Al-Ghalith GA, et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol 2019;37:852-857.
45. Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, et al. Metagenomic biomarker discovery and explanation. Genome Biol 2011;12(6):R60.
46. Fritz CO, Morris PE, Richler JJ. Effect size estimates: Current use, calculations, and interpretation. J Exp Psychol Gen 2012;141:2-18.
47. Anderson MJ. Permutational multivariate analysis of variance (PERMANOVA). Wiley StatsRef: Statistics Reference Online 2017:1-15.
48. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Methodol 1995;57:289-300.
49. Zimmermann MB, Hurrell RF. Iron deficiency and the gut microbiome. Annu Rev Nutr 2017;37:131-157.
50. Dostal A, Chassard C, Hilty FM, Zimmermann MB, Lacroix C. Iron depletion modifies gut microbiota composition. J Nutr 2015;145:1312-1320.
51. Kortman GAM, Raffatellu M, Swinkels DW, Tjalsma H. Interactions between iron metabolism and the gut microbiome. Nat Rev Gastroenterol Hepatol 2014;11:411-423.
| Files | ||
| Issue | Vol 18 No 2 (2026) | |
| Section | Original Article(s) | |
| Keywords | ||
| Iron-deficiency anemia Gut microbiome Intestinal microbiota Iron metabolism Enterobacteriaceae Lactobacillus Iron supplementation Dysbiosis | ||
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How to Cite
1.
Abd El Rahmen R, Alghamdi K. Gut microbiome signatures associated with iron-deficiency anemia in young adults. Iran J Microbiol. 2026;18(2):186-196.
