{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T10:33:36Z","timestamp":1787567616616,"version":"build-2736575974"},"reference-count":187,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T00:00:00Z","timestamp":1787443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["224315"],"award-info":[{"award-number":["224315"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["226014"],"award-info":[{"award-number":["226014"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"award":["224315"],"award-info":[{"award-number":["224315"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"publisher"}]},{"award":["226014"],"award-info":[{"award-number":["226014"]}],"id":[{"id":"https:\/\/ror.org\/029chgv08","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Severe anaemia remains a major public health challenge, disproportionately affecting children and women of reproductive age in sub-Saharan Africa. In high-burden settings, the aetiology of severe anaemia is multifactorial, encompassing nutritional deficiencies, infections, and host genetic factors. Beyond its direct clinical consequences, severe anaemia is also associated with increased susceptibility to invasive bacterial infections, particularly those caused by enteric pathogens such as non-typhoidal Salmonella and Escherichia coli. In this review, we present an integrated framework linking severe anaemia and invasive bacterial infection through three interconnected biological pathways, collectively termed the gut\u2013iron\u2013immune axis: gut microbial dysbiosis and impaired intestinal barrier integrity; disrupted iron homeostasis; and impaired immune function. We examine context-specific modifiers in endemic settings, including iron deficiency, malnutrition, malaria, sickle cell disease, and environmental enteric dysfunction. We also discuss how management of severe anaemia, including blood transfusion and iron supplementation, reshapes the gut microbiome, with direct implications for microbial translocation, invasive bacterial infection, and clinical outcomes. Finally, we identify key knowledge gaps and research priorities to guide safer and more effective prevention and management of severe anaemia in high-burden settings.<\/jats:p>","DOI":"10.3390\/nu18172753","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:20:02Z","timestamp":1787563202000},"page":"2753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Gut\u2013Iron\u2013Immune Axis in Severe Anaemia and Bacteraemia"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5726-1776","authenticated-orcid":false,"given":"Kelvin Mokaya","family":"Abuga","sequence":"first","affiliation":[{"name":"Kenya Medical Research Institute (KEMRI) Centre for Geographic Medicine Research, KEMRI-Wellcome Trust Research Programme, Kilifi P.O. Box 230-80108, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6272-2960","authenticated-orcid":false,"given":"Miranda Y.","family":"Bate","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8360-4402","authenticated-orcid":false,"given":"Sarah H.","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Kenya Medical Research Institute (KEMRI) Centre for Geographic Medicine Research, KEMRI-Wellcome Trust Research Programme, Kilifi P.O. Box 230-80108, Kenya"},{"name":"Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford OX3 7LF, UK"},{"name":"Department of Paediatrics, University of Oxford, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,23]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024). Guideline on Haemoglobin Cutoffs to Define Anaemia in Individuals and Populations, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e627","DOI":"10.1016\/S2214-109X(22)00084-5","article-title":"National, regional, and global estimates of anaemia by severity in women and children for 2000\u201319: A pooled analysis of population-representative data","volume":"10","author":"Stevens","year":"2022","journal-title":"Lancet Glob. Health"},{"key":"ref_3","unstructured":"Global Burden of Disease Anaemia Collaborators (2023). Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990\u20132021: Findings from the Global Burden of Disease Study 2021. Lancet Haematol., 10, e713\u2013e734."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Chami, N., Hau, D.K., Masoza, T.S., Smart, L.R., Kayange, N.M., Hokororo, A., Ambrose, E.E., Moschovis, P.P., Wiens, M.O., and Peck, R.N. (2019). Very severe anemia and one year mortality outcome after hospitalization in Tanzanian children: A prospective cohort study. PLoS ONE, 14.","DOI":"10.1101\/581462"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Simbauranga, R.H., Kamugisha, E., Hokororo, A., Kidenya, B.R., and Makani, J. (2015). Prevalence and factors associated with severe anaemia amongst under-five children hospitalized at Bugando Medical Centre, Mwanza, Tanzania. BMC Hematol., 15.","DOI":"10.1186\/s12878-015-0033-5"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"103976","DOI":"10.1016\/j.langlo.2026.103976","article-title":"Severe anaemia and invasive bacterial infections in Kenyan children: A 26-year hospital surveillance observational study","volume":"14","author":"Abuga","year":"2026","journal-title":"Lancet Glob. Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1056\/NEJMoa072727","article-title":"Severe anemia in Malawian children","volume":"358","author":"Calis","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Church, J., and Maitland, K. (2014). Invasive bacterial co-infection in African children with Plasmodium falciparum malaria: A systematic review. BMC Med., 12.","DOI":"10.1186\/1741-7015-12-31"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1016\/S0140-6736(09)61374-X","article-title":"Bacteraemia in Kenyan children with sickle-cell anaemia: A retrospective cohort and case-control study","volume":"374","author":"Williams","year":"2009","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1056\/NEJMoa040275","article-title":"Bacteremia among children admitted to a rural hospital in Kenya","volume":"352","author":"Berkley","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"48","DOI":"10.12688\/wellcomeopenres.18829.1","article-title":"Severe anaemia, iron deficiency, and susceptibility to invasive bacterial infections","volume":"8","author":"Abuga","year":"2023","journal-title":"Wellcome Open Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1002\/JLB.3RI1018-400R","article-title":"Malaria, anemia, and invasive bacterial disease: A neutrophil problem?","volume":"105","author":"Mooney","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1038\/s41564-025-02001-y","article-title":"Iron at the crossroads of host-microbiome interactions in health and disease","volume":"10","author":"Choi","year":"2025","journal-title":"Nat. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1007\/s00018-018-2943-4","article-title":"An insight into gut microbiota and its functionalities","volume":"76","author":"Adak","year":"2019","journal-title":"Cell Mol. Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/nature18847","article-title":"The microbiome and innate immunity","volume":"535","author":"Thaiss","year":"2016","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"R9","DOI":"10.1186\/cc9408","article-title":"Inflammation-induced hepcidin-25 is associated with the development of anemia in septic patients: An observational study","volume":"15","author":"Kroot","year":"2011","journal-title":"Crit. Care"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"11198","DOI":"10.1038\/s41598-018-29558-5","article-title":"Relationship between Anaemia, Haemolysis, Inflammation and Haem Oxygenase-1 at Admission with Sepsis: A pilot study","volume":"8","author":"Ekregbesi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00109-006-0123-8","article-title":"Suicidal erythrocyte death in sepsis","volume":"85","author":"Kempe","year":"2007","journal-title":"J. Mol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.tim.2018.09.008","article-title":"The Human Microbiome and Child Growth\u2014First 1000 Days and Beyond","volume":"27","author":"Robertson","year":"2019","journal-title":"Trends Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/nri2515","article-title":"The gut microbiota shapes intestinal immune responses during health and disease","volume":"9","author":"Round","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1038\/ng.3663","article-title":"The effect of host genetics on the gut microbiome","volume":"48","author":"Bonder","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Sender, R., Fuchs, S., and Milo, R. (2016). Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol., 14.","DOI":"10.1101\/036103"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.cell.2016.01.013","article-title":"Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans","volume":"164","author":"Sender","year":"2016","journal-title":"Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1126\/science.aaf3951","article-title":"Cospeciation of gut microbiota with hominids","volume":"353","author":"Moeller","year":"2016","journal-title":"Science"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1038\/nrmicro1978","article-title":"Worlds within worlds: Evolution of the vertebrate gut microbiota","volume":"6","author":"Ley","year":"2008","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.chom.2018.05.012","article-title":"The Impact of Dietary Fiber on Gut Microbiota in Host Health and Disease","volume":"23","author":"Makki","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Dagbasi, A., Cai, M., Hirdaramani, A., Hanyaloglu, A., Morrison, D.J., and Frost, G. (2026). Short-chain fatty acids. Nat. Metab.","DOI":"10.1038\/s42255-026-01579-9"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41579-022-00805-x","article-title":"Bile acids and the gut microbiota: Metabolic interactions and impacts on disease","volume":"21","author":"Collins","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2083","DOI":"10.1007\/s00726-017-2493-3","article-title":"A review of the relationship between the gut microbiota and amino acid metabolism","volume":"49","author":"Lin","year":"2017","journal-title":"Amino Acids"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.copbio.2012.08.005","article-title":"Bacteria as vitamin suppliers to their host: A gut microbiota perspective","volume":"24","author":"LeBlanc","year":"2013","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1995S","DOI":"10.1093\/jn\/nxy201","article-title":"Biomarkers of Nutrition for Development (BOND): Vitamin B-12 Review","volume":"148","author":"Allen","year":"2018","journal-title":"J. Nutr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1636S","DOI":"10.3945\/jn.114.206599","article-title":"Biomarkers of Nutrition for Development-Folate Review","volume":"145","author":"Bailey","year":"2015","journal-title":"J. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.3945\/ajcn.114.091785","article-title":"Folate is absorbed across the human colon: Evidence by using enteric-coated caplets containing 13C-labeled [6S]-5-formyltetrahydrofolate","volume":"100","author":"Lakoff","year":"2014","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.cmet.2014.10.002","article-title":"Vitamin B12 as a modulator of gut microbial ecology","volume":"20","author":"Degnan","year":"2014","journal-title":"Cell Metab."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Skaar, E.P. (2010). The battle for iron between bacterial pathogens and their vertebrate hosts. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000949"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41579-022-00745-6","article-title":"Nutritional immunity: The battle for nutrient metals at the host-pathogen interface","volume":"20","author":"Murdoch","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"127093","DOI":"10.1016\/j.jtemb.2022.127093","article-title":"Iron in infectious diseases friend or foe?: The role of gut microbiota","volume":"75","author":"Aksoyalp","year":"2023","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1080\/003655202320378176","article-title":"Influence of short-chain fatty acids on iron absorption by proximal colon","volume":"37","author":"Roland","year":"2002","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9017","DOI":"10.1080\/10408398.2022.2060933","article-title":"Effects of dietary fiber on intestinal iron absorption, and physiological status: A systematic review of in vivo and clinical studies","volume":"63","author":"Agarwal","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.stem.2021.12.009","article-title":"The microbiota regulates hematopoietic stem cell fate decisions by controlling iron availability in bone marrow","volume":"29","author":"Zhang","year":"2022","journal-title":"Cell Stem Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1126\/science.aau6481","article-title":"Dendritic cell-derived hepcidin sequesters iron from the microbiota to promote mucosal healing","volume":"368","author":"Bessman","year":"2020","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"30637","DOI":"10.1074\/jbc.M115.689190","article-title":"Commensal Bacteria-induced Interleukin 1beta (IL-1beta) Secreted by Macrophages Up-regulates Hepcidin Expression in Hepatocytes by Activating the Bone Morphogenetic Protein Signaling Pathway","volume":"290","author":"Shanmugam","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Vega-Bautista, A., de la Garza, M., Carrero, J.C., Campos-Rodr\u00edguez, R., God\u00ednez-Victoria, M., and Drago-Serrano, M.E. (2019). The Impact of Lactoferrin on the Growth of Intestinal Inhabitant Bacteria. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194707"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1146\/annurev-med-043021-032816","article-title":"Hepcidin and Iron in Health and Disease","volume":"74","author":"Nemeth","year":"2023","journal-title":"Annu. Rev. Med."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Le\u00f3n, E.D., and Francino, M.P. (2022). Roles of Secretory Immunoglobulin A in Host-Microbiota Interactions in the Gut Ecosystem. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.880484"},{"key":"ref_46","first-page":"1","article-title":"Overview of gut immunology","volume":"Volumn 635","author":"Mason","year":"2008","journal-title":"GI Microbiota and Regulation of the Immune System"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wiertsema, S.P., van Bergenhenegouwen, J., Garssen, J., and Knippels, L.M.J. (2021). The Interplay between the Gut Microbiome and the Immune System in the Context of Infectious Diseases throughout Life and the Role of Nutrition in Optimizing Treatment Strategies. Nutrients, 13.","DOI":"10.3390\/nu13030886"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/s41579-022-00833-7","article-title":"Microbiota-mediated colonization resistance: Mechanisms and regulation","volume":"21","author":"Pickard","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Bao, H., Wang, Y., Xiong, H., Xia, Y., Cui, Z., and Liu, L. (2024). Mechanism of Iron Ion Homeostasis in Intestinal Immunity and Gut Microbiota Remodeling. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25020727"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1874855","DOI":"10.1080\/19490976.2021.1874855","article-title":"Iron homeostasis in host and gut bacteria\u2014A complex interrelationship","volume":"13","author":"Seyoum","year":"2021","journal-title":"Gut Microbes"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Yilmaz, B., and Li, H. (2018). Gut Microbiota and Iron: The Crucial Actors in Health and Disease. Pharmaceuticals, 11.","DOI":"10.3390\/ph11040098"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1182\/blood-2016-03-708594","article-title":"Antibiotics impair murine hematopoiesis by depleting the intestinal microbiota","volume":"129","author":"Josefsdottir","year":"2017","journal-title":"Blood"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Long, Y., Liang, F., Guo, R., Zhu, C., Zhao, X., Wang, X., Liu, F., Jiang, M., Liang, Q., and Zeng, S. (2021). Gut Microbiota Signatures in Gestational Anemia. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.549678"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Wei, H., Deng, S., Qin, Y., Yang, X., Chen, T., Wang, X., and Xia, Y. (2021). Insight Into the Potential Value of Gut Microbial Signatures for Prediction of Gestational Anemia. Front. Cell. Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.734561"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Coll, E., Cigarran, S., Portoles, J., and Cases, A. (2024). Gut Dysbiosis and Its Role in the Anemia of Chronic Kidney Disease. Toxins, 16.","DOI":"10.3390\/toxins16110495"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Tesoi, D.F., Trandafir, L.M., Bozomitu, L., Frasinariu, O.E., Filip, N., Mircea, C., Hancianu, M., and Badulescu, O.V. (2026). Molecular Mechanisms Underlying the Higher Prevalence of Anemia in Crohn\u2019s Disease Compared with Ulcerative Colitis: A Systematic Review. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27125570"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Zhou, H., Fan, Z., Da, Y., Liu, X., Wang, C., Zhang, T., Zhang, J., Wu, T., and Liang, J. (2025). Causal Relationships Between Iron Deficiency Anemia, Gut Microbiota, and Metabolites: Insights from Mendelian Randomization and In Vivo Data. Biomedicines, 13.","DOI":"10.3390\/biomedicines13030677"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e41617","DOI":"10.1097\/MD.0000000000041617","article-title":"Gut microbiota and risk of iron deficiency anemia: A two-sample Mendelian randomization study","volume":"104","author":"Lei","year":"2025","journal-title":"Medicine"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Su, T., Peng, X., Gan, Y., Wu, H., Ma, S., Zhi, M., Lu, Y., Dai, S., and Yao, J. (2024). Associations of genetically predicted iron status with 24 gastrointestinal diseases and gut microbiota: A Mendelian randomization study. Front. Genet., 15.","DOI":"10.3389\/fgene.2024.1406230"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2549962","DOI":"10.1080\/16078454.2025.2549962","article-title":"The relationship between gut microbiota, plasma metabolites, and iron deficiency anemia in European populations: A three-sample Mendelian randomization analysis","volume":"30","author":"Zheng","year":"2025","journal-title":"Hematology"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1111\/trf.15254","article-title":"Anemia induces gut inflammation and injury in an animal model of preterm infants","volume":"59","author":"Arthur","year":"2019","journal-title":"Transfusion"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"G705","DOI":"10.1152\/ajpgi.00324.2019","article-title":"Severe neonatal anemia increases intestinal permeability by disrupting epithelial adherens junctions","volume":"318","author":"MohanKumar","year":"2020","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1093\/ajcn\/nqy249","article-title":"Anemia in infancy is associated with alterations in systemic metabolism and microbial structure and function in a sex-specific manner: An observational study","volume":"108","author":"McClorry","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Diaz-Rodriguez, K., Pacheco-Aranibar, J., Manrique-Sam, C., Ita-Balta, Y., Carpio-Toia, A.M.D., Lopez-Casaperalta, P., Chocano-Rosas, T., Fernandez, F.F., Villanueva-Salas, J., and Bernabe-Ortiz, J.C. (2022). Intestinal Microbiota in Children with Anemia in Southern Peru through Next-Generation Sequencing Technology. Children, 9.","DOI":"10.3390\/children9111615"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5204","DOI":"10.1038\/s41467-024-49093-4","article-title":"Faecal microbiota of schoolchildren is associated with nutritional status and markers of inflammation: A double-blinded cluster-randomized controlled trial using multi-micronutrient fortified rice","volume":"15","author":"Seyoum","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1038\/s41372-020-0599-z","article-title":"The development of intestinal dysbiosis in anemic preterm infants","volume":"40","author":"Ho","year":"2020","journal-title":"J. Perinatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2415","DOI":"10.1038\/s41390-024-03669-4","article-title":"Severe anemia in preterm infants associated with increased bacterial virulence potential and metabolic disequilibrium","volume":"97","author":"Gibbons","year":"2025","journal-title":"Pediatr. Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1038\/s41390-021-01903-x","article-title":"Neonatal anemia relates to intestinal injury in preterm infants","volume":"91","author":"Kalteren","year":"2022","journal-title":"Pediatr. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"101615","DOI":"10.1016\/j.siny.2025.101615","article-title":"Severe anemia predisposes very premature infants to transfusion-associated necrotizing enterocolitis","volume":"30","author":"Maheshwari","year":"2025","journal-title":"Semin. Fetal Neonatal Med."},{"key":"ref_70","first-page":"5","article-title":"Metagenomics, Metatranscriptomics, and Metabolomics Approaches for Microbiome Analysis","volume":"12","author":"Huang","year":"2016","journal-title":"Evol. Bioinform."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1017\/S0007114510001637","article-title":"Low levels of faecal lactobacilli in women with iron-deficiency anaemia in south India","volume":"104","author":"Balamurugan","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1556\/030.65.2018.045","article-title":"Iron deficiency anemia-related gut microbiota dysbiosis in infants and young children: A pilot study","volume":"65","author":"Muleviciene","year":"2018","journal-title":"Acta Microbiol. Immunol. Hung."},{"key":"ref_73","first-page":"923","article-title":"Altered fecal microbial and metabolic profile reveals potential mechanisms underlying iron deficiency anemia in pregnant women in China","volume":"22","author":"Chen","year":"2022","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Seo, H., Yoon, S.Y., Ul-Haq, A., Jo, S., Kim, S., Rahim, M.A., Park, H.A., Ghorbanian, F., Kim, M.J., and Lee, M.Y. (2023). The Effects of Iron Deficiency on the Gut Microbiota in Women of Childbearing Age. Nutrients, 15.","DOI":"10.3390\/nu15030691"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/jhn.13171","article-title":"Associations of HIV and iron status with gut microbiota composition, gut inflammation and gut integrity in South African school-age children: A two-way factorial case-control study","volume":"36","author":"Goosen","year":"2023","journal-title":"J. Hum. Nutr. Diet."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"E91","DOI":"10.1002\/ajh.25019","article-title":"Intestinal microbiome analysis revealed dysbiosis in sickle cell disease","volume":"93","author":"Lim","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5360","DOI":"10.1111\/jcmm.17402","article-title":"Microbial gut evaluation in an angolan paediatric population with sickle cell disease","volume":"26","author":"Delgadinho","year":"2022","journal-title":"J. Cell. Mol. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"e904","DOI":"10.1097\/MPH.0000000000002725","article-title":"Evaluation of Intestinal Microbiota in Children With Sickle Cell Disease","volume":"45","author":"Karahan","year":"2023","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Brim, H., Taylor, J., Abbas, M., Vilmenay, K., Daremipouran, M., Varma, S., Lee, E., Pace, B., Song-Naba, W.L., and Gupta, K. (2021). The gut microbiome in sickle cell disease: Characterization and potential implications. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0255956"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e30397","DOI":"10.1002\/pbc.30397","article-title":"The relationship between nutrition, gut dysbiosis, and pediatric sickle cell pain outcomes: A pilot study","volume":"70","author":"Dike","year":"2023","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"109094","DOI":"10.1016\/j.celrep.2021.109094","article-title":"Dynamic modulation of spleen germinal center reactions by gut bacteria during Plasmodium infection","volume":"35","author":"Mandal","year":"2021","journal-title":"Cell Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e14072","DOI":"10.1111\/eci.14072","article-title":"Washed microbiota transplantation improves haemoglobin levels in anaemia of chronic disease","volume":"53","author":"Zhong","year":"2023","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e0316624","DOI":"10.1128\/spectrum.03166-24","article-title":"Altered fecal microbial and metabolic profiles reveal potential mechanisms underlying anemia in patients with chronic renal failure","volume":"13","author":"Wang","year":"2025","journal-title":"Microbiol. Spectr."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Shao, Y., Qi, W., Zhang, X., Ran, N., Liu, C., Fu, R., and Shao, Z. (2021). Plasma Metabolomic and Intestinal Microbial Analyses of Patients With Severe Aplastic Anemia. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.669887"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4013","DOI":"10.1007\/s00277-025-06459-y","article-title":"Analysis of fecal microbiome in Chinese patients with non-severe aplastic anemia","volume":"104","author":"Zhang","year":"2025","journal-title":"Ann. Hematol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1182\/blood-2018-05-815944","article-title":"Iron deficiency","volume":"133","author":"Camaschella","year":"2019","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"100701","DOI":"10.1016\/j.bj.2024.100701","article-title":"Comprehensive insight into the alterations in the gut microbiome and the intestinal barrier as a consequence of iron deficiency anaemia","volume":"47","author":"Barton","year":"2024","journal-title":"Biomed. J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"109065","DOI":"10.1016\/j.jnutbio.2022.109065","article-title":"Iron deficient diets modify the gut microbiome and reduce the severity of enteric infection in a mouse model of S. Typhimurium-induced enterocolitis","volume":"107","author":"Ippolito","year":"2022","journal-title":"J. Nutr. Biochem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"14298","DOI":"10.1038\/s41598-026-44373-z","article-title":"Molecular study of the small intestine dysbiosis derived from iron deficiency anaemia","volume":"16","author":"Alferez","year":"2026","journal-title":"Sci. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3945\/jn.111.148643","article-title":"Iron depletion and repletion with ferrous sulfate or electrolytic iron modifies the composition and metabolic activity of the gut microbiota in rats","volume":"142","author":"Dostal","year":"2012","journal-title":"J. Nutr."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1002\/mbo3.213","article-title":"Dietary iron depletion at weaning imprints low microbiome diversity and this is not recovered with oral Nano Fe(III)","volume":"4","author":"Pereira","year":"2015","journal-title":"Microbiologyopen"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e01453-15","DOI":"10.1128\/mBio.01453-15","article-title":"Iron Modulates Butyrate Production by a Child Gut Microbiota In Vitro","volume":"6","author":"Dostal","year":"2015","journal-title":"mBio"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"15668","DOI":"10.1021\/acs.jafc.3c05560","article-title":"Fermented Goat\u2019s Milk Contributes to the Recovery of Iron Deficiency Anemia via Modulation of the Gut Microbiome","volume":"71","author":"Alferez","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.chembiol.2022.12.001","article-title":"The impact of iron and heme availability on the healthy human gut microbiome in vivo and in vitro","volume":"30","author":"Celis","year":"2023","journal-title":"Cell Chem. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1038\/s41574-022-00721-3","article-title":"The role of iron in host-microbiota crosstalk and its effects on systemic glucose metabolism","volume":"18","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_96","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_97","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_98","unstructured":"World Health Organization (2025). World Malaria Report 2025: Addressing the Threat of Antimalarial Drug Resistance, World Health Organization."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1186\/s12936-018-2509-9","article-title":"Anaemia and malaria","volume":"17","author":"White","year":"2018","journal-title":"Malar. J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.7150\/ijbs.7.1427","article-title":"Severe malarial anemia: Innate immunity and pathogenesis","volume":"7","author":"Perkins","year":"2011","journal-title":"Int. J. Biol. Sci."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Olupot-Olupot, P., Urban, B.C., Jemutai, J., Nteziyaremye, J., Fanjo, H.M., Karanja, H., Karisa, J., Ongodia, P., Bwonyo, P., and Gitau, E.N. (2013). Endotoxaemia is common in children with Plasmodium falciparum malaria. BMC Infect. Dis., 13.","DOI":"10.1186\/1471-2334-13-117"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.3324\/haematol.2021.279316","article-title":"Hepcidin regulation in Kenyan children with severe malaria and non-typhoidal Salmonella bacteremia","volume":"107","author":"Abuga","year":"2022","journal-title":"Haematologica"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.pt.2013.03.006","article-title":"The iron link between malaria and invasive non-typhoid Salmonella infections","volume":"29","author":"Swinkels","year":"2013","journal-title":"Trends Parasitol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1093\/clinids\/24.3.430","article-title":"Increased gastrointestinal permeability in patients with Plasmodium falciparum malaria","volume":"24","author":"Wilairatana","year":"1997","journal-title":"Clin. Infect. Dis."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e0132522","DOI":"10.1128\/mbio.01325-22","article-title":"Intestinal Injury Biomarkers Predict Mortality in Pediatric Severe Malaria","volume":"13","author":"Sarangam","year":"2022","journal-title":"mBio"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"9658","DOI":"10.1038\/s41467-025-64632-3","article-title":"Gut bacterial dysbiosis in pediatric severe malaria associates with post-discharge mortality","volume":"16","author":"Bednarski","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1056\/NEJMra1510865","article-title":"Sickle Cell Disease","volume":"376","author":"Piel","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1096\/fba.2022-00121","article-title":"Intestinal barrier dysfunction in murine sickle cell disease is associated with small intestine neutrophilic inflammation, oxidative stress, and dysbiosis","volume":"5","author":"Lewis","year":"2023","journal-title":"FASEB Bioadvances"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1111\/bjh.17889","article-title":"Intestinal pathophysiological abnormalities in steady state and after vaso-occlusive crisis in murine sickle cell disease","volume":"196","author":"Poplawska","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1186\/s12967-019-1938-8","article-title":"Intestinal injury and gut permeability in sickle cell disease","volume":"17","author":"Dutta","year":"2019","journal-title":"J. Transl. Med."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1016\/j.chom.2025.08.012","article-title":"Gut microbiota and metabolites drive chronic sickle cell disease pain in mice","volume":"33","author":"Brandow","year":"2025","journal-title":"Cell Host Microbe"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.immuni.2020.06.025","article-title":"The Gut Microbiome Regulates Psychological-Stress-Induced Inflammation","volume":"53","author":"Xu","year":"2020","journal-title":"Immunity"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1182\/blood.2022016218","article-title":"Dietary iron restriction protects against vaso-occlusion and organ damage in murine sickle cell disease","volume":"141","author":"Li","year":"2023","journal-title":"Blood"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Delgadinho, M., Ginete, C., Santos, B., Fernandes, C., Silva, C., Miranda, A., Vasconcelos, J.N., and Brito, M. (2022). How Hydroxyurea Alters the Gut Microbiome: A Longitudinal Study Involving Angolan Children with Sickle Cell Anemia. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169061"},{"key":"ref_115","first-page":"e65633","article-title":"Prevalence of Iron Deficiency Anemia and Iron Deficiency Without Anemia Among Moderate and Severely Acute Malnourished Children","volume":"16","author":"Suhas","year":"2024","journal-title":"Cureus"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1046\/j.1442-200x.2000.01217.x","article-title":"Altered anti-oxidant status and increased lipid peroxidation in marasmic children","volume":"42","author":"Tatli","year":"2000","journal-title":"Pediatr. Int."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1067\/mpd.2000.107512","article-title":"Increased oxidative stress in kwashiorkor","volume":"137","author":"Manary","year":"2000","journal-title":"J. Pediatr."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nature13421","article-title":"Persistent gut microbiota immaturity in malnourished Bangladeshi children","volume":"510","author":"Subramanian","year":"2014","journal-title":"Nature"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"114640","DOI":"10.1016\/j.isci.2026.114640","article-title":"Gut microbial diversity impacts carbohydrate fermentation by children with severe acute malnutrition","volume":"29","author":"Bisht","year":"2026","journal-title":"iScience"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"103644","DOI":"10.1016\/j.ebiom.2021.103644","article-title":"Interactions between fecal gut microbiome, enteric pathogens, and energy regulating hormones among acutely malnourished rural Gambian children","volume":"73","author":"Nabwera","year":"2021","journal-title":"EBioMedicine"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1093\/ajcn\/nqz151","article-title":"Intestinal permeability and inflammation mediate the association between nutrient density of complementary foods and biochemical measures of micronutrient status in young children: Results from the MAL-ED study","volume":"110","author":"McCormick","year":"2019","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"33","DOI":"10.2147\/PHMT.S387747","article-title":"Environmental Enteropathy and Anaemia Status Among Under-Five Children, in Slum Areas of Jimma Town, Ethiopia","volume":"14","author":"Regassa","year":"2023","journal-title":"Pediatr. Health Med. Ther."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1093\/jn\/nxaa141","article-title":"Markers of Environmental Enteric Dysfunction Are Associated with Poor Growth and Iron Status in Rural Ugandan Infants","volume":"150","author":"Lauer","year":"2020","journal-title":"J. Nutr."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"S76","DOI":"10.1177\/15648265150361S113","article-title":"Environmental enteric dysfunction: An overview","volume":"36","author":"Crane","year":"2015","journal-title":"Food Nutr. Bull."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1007\/s00109-007-0277-z","article-title":"Hypoxia and gastrointestinal disease","volume":"85","author":"Taylor","year":"2007","journal-title":"J. Mol. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"10493","DOI":"10.1074\/jbc.REV120.011188","article-title":"Oxygen battle in the gut: Hypoxia and hypoxia-inducible factors in metabolic and inflammatory responses in the intestine","volume":"295","author":"Singhal","year":"2020","journal-title":"J. Biol. Chem."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"eaat9076","DOI":"10.1126\/science.aat9076","article-title":"Colonocyte metabolism shapes the gut microbiota","volume":"362","author":"Litvak","year":"2018","journal-title":"Science"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.freeradbiomed.2016.09.022","article-title":"Oxygen as a driver of gut dysbiosis","volume":"105","author":"Lopez","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s13099-025-00783-4","article-title":"Intestinal oxygen and microbiota crosstalk: Implications for pathogenesis of gastrointestinal diseases and emerging therapeutic strategies","volume":"17","author":"Shang","year":"2025","journal-title":"Gut Pathog."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1182\/blood-2017-03-772715","article-title":"Endogenous hepcidin and its agonist mediate resistance to selected infections by clearing non-transferrin-bound iron","volume":"130","author":"Stefanova","year":"2017","journal-title":"Blood"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"e92002","DOI":"10.1172\/jci.insight.92002","article-title":"Hepcidin-mediated iron sequestration protects against bacterial dissemination during pneumonia","volume":"2","author":"Michels","year":"2017","journal-title":"JCI Insight"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3324\/haematol.2016.150227","article-title":"Erythroferrone contributes to hepcidin repression in a mouse model of malarial anemia","volume":"102","author":"Latour","year":"2017","journal-title":"Haematologica"},{"key":"ref_133","doi-asserted-by":"crossref","unstructured":"Jonker, F.A., Calis, J.C., Phiri, K., Kraaijenhagen, R.J., Brabin, B.J., Faragher, B., Wiegerinck, E.T., Tjalsma, H., Swinkels, D.W., and van Hensbroek, M.B. (2013). Low hepcidin levels in severely anemic malawian children with high incidence of infectious diseases and bone marrow iron deficiency. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0078964"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1182\/blood.2022015596","article-title":"Hemolysis, free hemoglobin toxicity, and scavenger protein therapeutics","volume":"140","author":"Vallelian","year":"2022","journal-title":"Blood"},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Abuga, K.M., Muriuki, J.M., Williams, T.N., and Atkinson, S.H. (2020). How Severe Anaemia Might Influence the Risk of Invasive Bacterial Infections in African Children. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186976"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"eabq5384","DOI":"10.1126\/sciadv.abq5384","article-title":"Plasma iron controls neutrophil production and function","volume":"8","author":"Frost","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"eaaw9522","DOI":"10.1126\/scitranslmed.aaw9522","article-title":"Immune system development varies according to age, location, and anemia in African children","volume":"12","author":"Hill","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1016\/S0140-6736(76)92647-7","article-title":"Anaemia and immune response","volume":"307","author":"Srikantia","year":"1976","journal-title":"Lancet"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/S0022-3476(75)80211-3","article-title":"The immune response in iron-deficient children: Impaired cellular defense mechanisms with altered humoral components","volume":"86","author":"Macdougall","year":"1975","journal-title":"J. Pediatr."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1038\/s41467-019-11002-5","article-title":"Iron-dependent histone 3 lysine 9 demethylation controls B cell proliferation and humoral immune responses","volume":"10","author":"Jiang","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"158","DOI":"10.4103\/0976-9668.127317","article-title":"Impact of iron deficiency anemia on cell-mediated and humoral immunity in children: A case control study","volume":"5","author":"Das","year":"2014","journal-title":"J. Nat. Sci. Biol. Med."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"e00533-16","DOI":"10.1128\/CVI.00533-16","article-title":"Cytokine Profiles in Malawian Children Presenting with Uncomplicated Malaria, Severe Malarial Anemia, and Cerebral Malaria","volume":"24","author":"Mandala","year":"2017","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Raballah, E., Kempaiah, P., Karim, Z., Orinda, G.O., Otieno, M.F., Perkins, D.J., and Ong\u2019echa, J.M. (2017). CD4 T-cell expression of IFN-gamma and IL-17 in pediatric malarial anemia. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0175864"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"e70013","DOI":"10.1002\/iid3.70013","article-title":"Pro- and anti-inflammatory cytokines mediate the progression of severe anemia in malaria-infected children: A prospective study","volume":"12","author":"Nkansah","year":"2024","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1038\/s41467-023-38444-2","article-title":"Microbiota-assisted iron uptake promotes immune tolerance in the intestine","volume":"14","author":"Zhu","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1146\/annurev-pathmechdis-012418-012838","article-title":"Pathophysiology of Sickle Cell Disease","volume":"14","author":"Sundd","year":"2019","journal-title":"Annu. Rev. Pathol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"G11","DOI":"10.1152\/ajpgi.00113.2021","article-title":"Biomarkers for assessment of intestinal permeability in clinical practice","volume":"321","author":"Seethaler","year":"2021","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_148","doi-asserted-by":"crossref","unstructured":"Perez-Diaz-Del-Campo, N., Castelnuovo, G., Ribaldone, D.G., and Caviglia, G.P. (2023). Fecal and Circulating Biomarkers for the Non-Invasive Assessment of Intestinal Permeability. Diagnostics, 13.","DOI":"10.3390\/diagnostics13111976"},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41580-023-00648-1","article-title":"Mechanisms controlling cellular and systemic iron homeostasis","volume":"25","author":"Galy","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1001S","DOI":"10.1093\/jn\/nxx036","article-title":"Biomarkers of Nutrition for Development (BOND)-Iron Review","volume":"148","author":"Lynch","year":"2018","journal-title":"J. Nutr."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.1002\/jcp.30247","article-title":"Erythroferrone structure, function, and physiology: Iron homeostasis and beyond","volume":"236","author":"Srole","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"ref_152","first-page":"95","article-title":"Biomarkers in immunology: Their impact on immune function and response","volume":"7","author":"Kaushik","year":"2025","journal-title":"Adv. Biomark. Sci. Technol."},{"key":"ref_153","unstructured":"World Health Organization (2013). Pocket Book of Hospital Care for Children: Guidelines for the Management of Common Childhood Illnesses, World Health Organization. [2nd ed.]."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"e717","DOI":"10.1016\/S2352-3026(25)00146-2","article-title":"Getting back on track to meet global anaemia reduction targets: A Lancet Haematology Commission","volume":"12","author":"Atkinson","year":"2025","journal-title":"Lancet Haematol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"e931","DOI":"10.1016\/S2666-5247(23)00213-6","article-title":"Effect of amoxicillin on the gut microbiome of children with severe acute malnutrition in Madarounfa, Niger: A retrospective metagenomic analysis of a placebo-controlled trial","volume":"4","author":"Schwartz","year":"2023","journal-title":"Lancet Microbe"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1097\/TA.0000000000002201","article-title":"A prospective study in severely injured patients reveals an altered gut microbiome is associated with transfusion volume","volume":"86","author":"Nicholson","year":"2019","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"e1260","DOI":"10.1002\/mbo3.1260","article-title":"Impact of antibiotics on the human microbiome and consequences for host health","volume":"11","author":"Patangia","year":"2022","journal-title":"Microbiologyopen"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1097\/TA.0000000000003381","article-title":"Whole blood resuscitation restores intestinal perfusion and influences gut microbiome diversity","volume":"91","author":"Yracheta","year":"2021","journal-title":"J. Trauma Acute Care Surg."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1053\/j.semperi.2012.04.007","article-title":"Do transfusions cause necrotizing enterocolitis? The complementary role of randomized trials and observational studies","volume":"36","author":"Kirpalani","year":"2012","journal-title":"Semin. Perinatol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1053\/j.semperi.2016.09.021","article-title":"Should we believe in transfusion-associated enterocolitis? Applying a GRADE to the literature","volume":"41","author":"Hay","year":"2017","journal-title":"Semin. Perinatol."},{"key":"ref_161","first-page":"Cd008959","article-title":"Home fortification of foods with multiple micronutrient powders for health and nutrition in children under two years of age","volume":"2","author":"Suchdev","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_162","unstructured":"World Health Organization (2016). Guideline: Daily Iron Supplementation in Infants and Children, World Health Organization."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Tang, M., Frank, D.N., Hendricks, A.E., Ir, D., Esamai, F., Liechty, E., Hambidge, K.M., and Krebs, N.F. (2017). Iron in Micronutrient Powder Promotes an Unfavorable Gut Microbiota in Kenyan Infants. Nutrients, 9.","DOI":"10.3390\/nu9070776"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"e0527322","DOI":"10.1128\/spectrum.05273-22","article-title":"The Effect of Oral Iron Supplementation on Gut Microbial Composition: A Secondary Analysis of a Double-Blind, Randomized Controlled Trial among Cambodian Women of Reproductive Age","volume":"11","author":"Nearing","year":"2023","journal-title":"Microbiol. Spectr."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1136\/gutjnl-2017-314418","article-title":"Prebiotic galacto-oligosaccharides mitigate the adverse effects of iron fortification on the gut microbiome: A randomised controlled study in Kenyan infants","volume":"66","author":"Paganini","year":"2017","journal-title":"Gut"},{"key":"ref_166","first-page":"2095","article-title":"Administration of ferrous sulfate drops has significant effects on the gut microbiota of iron-sufficient infants: A randomised controlled study","volume":"68","author":"Lagerqvist","year":"2019","journal-title":"Gut"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"8640","DOI":"10.1038\/s41467-024-53013-x","article-title":"Effects of iron supplements and iron-containing micronutrient powders on the gut microbiome in Bangladeshi infants: A randomized controlled trial","volume":"15","author":"Baldi","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1017\/S0007114514001160","article-title":"Effects of iron supplementation on dominant bacterial groups in the gut, faecal SCFA and gut inflammation: A randomised, placebo-controlled intervention trial in South African children","volume":"112","author":"Dostal","year":"2014","journal-title":"Br. J. Nutr."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/j.tjnut.2024.03.014","article-title":"The Effect of Iron Supplements on the Gut Microbiome of Females of Reproductive Age: A Randomized Controlled Trial","volume":"154","author":"Elms","year":"2024","journal-title":"J. Nutr."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1017\/S0007114518001149","article-title":"Iron supplementation has minor effects on gut microbiota composition in overweight and obese women in early pregnancy","volume":"120","author":"Barrett","year":"2018","journal-title":"Br. J. Nutr."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Shearer, J., Shah, S., MacInnis, M.J., Shen-Tu, G., and Mu, C. (2024). Dose-Responsive Effects of Iron Supplementation on the Gut Microbiota in Middle-Aged Women. Nutrients, 16.","DOI":"10.3390\/nu16060786"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"2086","DOI":"10.1007\/s11427-022-2409-0","article-title":"Role of iron in host-microbiota interaction and its effects on intestinal mucosal growth and immune plasticity in a piglet model","volume":"66","author":"Dong","year":"2023","journal-title":"Sci. China Life Sci."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1080\/19490976.2019.1599794","article-title":"Dietary iron variably modulates assembly of the intestinal microbiota in colitis-resistant and colitis-susceptible mice","volume":"11","author":"Ellermann","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Chen, S., Wu, X., Wang, X., Shao, Y., Tu, Q., Yang, H., Yin, J., and Yin, Y. (2020). Responses of Intestinal Microbiota and Immunity to Increasing Dietary Levels of Iron Using a Piglet Model. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.603392"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Alexeev, E.E., He, X., Slupsky, C.M., and L\u00f6nnerdal, B. (2017). Effects of iron supplementation on growth, gut microbiota, metabolomics and cognitive development of rat pups. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179713"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1136\/gutjnl-2015-309940","article-title":"Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD","volume":"66","author":"Lee","year":"2017","journal-title":"Gut"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Mahalhal, A., Frau, A., Burkitt, M.D., Ijaz, U.Z., Lamb, C.A., Mansfield, J.C., Lewis, S., Pritchard, D.M., and Probert, C.S. (2021). Oral Ferric Maltol Does Not Adversely Affect the Intestinal Microbiome of Patients or Mice, But Ferrous Sulphate Does. Nutrients, 13.","DOI":"10.3390\/nu13072269"},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Zakrzewska, Z., Zawartka, A., Schab, M., Martyniak, A., Skoczen, S., Tomasik, P.J., and Wedrychowicz, A. (2022). Prebiotics, Probiotics, and Postbiotics in the Prevention and Treatment of Anemia. Microorganisms, 10.","DOI":"10.3390\/microorganisms10071330"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"2296","DOI":"10.1093\/advances\/nmac079","article-title":"The Effect of Prebiotics on Human Iron Absorption: A Review","volume":"13","author":"Husmann","year":"2022","journal-title":"Adv. Nutr."},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Hu, Q., Liu, Y., Fei, Y., Zhang, J., Yin, S., Zou, H., and Zhu, F. (2024). Efficacy of probiotic, prebiotic, and synbiotics supplements in individuals with anemia: A systematic review and meta-analysis of randomized controlled trials. BMC Gastroenterol., 24.","DOI":"10.1186\/s12876-024-03562-8"},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"El\u00edas Sol\u00eds, G.E., Pacori, S.A.M., Huancahuire-Vega, S., and Soriano-Moreno, D.R. (2026). Efficacy and safety of prebiotics, probiotics, and synbiotics on hemoglobin and anemia in the pediatric population: A systematic review and meta-analysis. PLoS ONE, 21.","DOI":"10.1371\/journal.pone.0354681"},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Apte, A., Parge, A., Nimkar, R., and Sinha, A. (2025). Effect of probiotic and prebiotics supplementation on hemoglobin levels and iron absorption among women of reproductive age and children: A systematic review and meta-analysis. BMC Nutr., 11.","DOI":"10.1186\/s40795-025-01015-3"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Qasem, W., Azad, M.B., Hossain, Z., Azad, E., Jorgensen, S., Castillo San Juan, S., Cai, C., Khafipour, E., Beta, T., and Roberts, L.J. (2017). Assessment of complementary feeding of Canadian infants: Effects on microbiome & oxidative stress, a randomized controlled trial. BMC Pediatr., 17.","DOI":"10.1186\/s12887-017-0805-0"},{"key":"ref_184","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_185","doi-asserted-by":"crossref","first-page":"e969","DOI":"10.1016\/S2666-5247(22)00203-8","article-title":"The gut mycobiome in health, disease, and clinical applications in association with the gut bacterial microbiome assembly","volume":"3","author":"Zhang","year":"2022","journal-title":"Lancet Microbe"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/s41575-025-01134-z","article-title":"Gut virome dynamics: From commensal to critical player in health and disease","volume":"23","author":"Leonard","year":"2026","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"100191","DOI":"10.1016\/j.engmic.2025.100191","article-title":"The gut virome and human health: From diversity to personalized medicine","volume":"5","author":"Lathakumari","year":"2025","journal-title":"Eng. Microbiol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/17\/2753\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:28:50Z","timestamp":1787563730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/17\/2753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,23]]},"references-count":187,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["nu18172753"],"URL":"https:\/\/doi.org\/10.3390\/nu18172753","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,23]]}}}