{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:59:04Z","timestamp":1789394344510,"version":"build-2803163510"},"reference-count":92,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2017\/25\/B\/NZ9\/01707"],"award-info":[{"award-number":["2017\/25\/B\/NZ9\/01707"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Iron deficiency is the most common mammalian nutritional disorder. However, among mammalian species iron deficiency anemia (IDA), occurs regularly only in pigs. To cure IDA, piglets are routinely injected with high amounts of iron dextran (FeDex), which can lead to perturbations in iron homeostasis. Here, we evaluate the therapeutic efficacy of non-invasive supplementation with Sucrosomial iron (SI), a highly bioavailable iron supplement preventing IDA in humans and mice and various iron oxide nanoparticles (IONPs). Analysis of red blood cell indices and plasma iron parameters shows that not all iron preparations used in the study efficiently counteracted IDA comparable to FeDex-based supplementation. We found no signs of iron toxicity of any tested iron compounds, as evaluated based on the measurement of several toxicological markers that could indicate the occurrence of oxidative stress or inflammation. Neither SI nor IONPs increased hepcidin expression with alterations in ferroportin (FPN) protein level. Finally, the analysis of the piglet gut microbiota indicates the individual pattern of bacterial diversity across taxonomic levels, independent of the type of supplementation. In light of our results, SI but not IONPs used in the experiment emerges as a promising nutritional iron supplement, with a high potential to correct IDA in piglets.<\/jats:p>","DOI":"10.3390\/ijms22189930","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T21:47:21Z","timestamp":1631656041000},"page":"9930","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Comparative Evaluation of Sucrosomial Iron and Iron Oxide Nanoparticles as Oral Supplements in Iron Deficiency Anemia in Piglets"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6706-0882","authenticated-orcid":false,"given":"Rafa\u0142","family":"Mazgaj","sequence":"first","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology PAS, 28-130 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Lipi\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology PAS, 28-130 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateusz","family":"Szudzik","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology PAS, 28-130 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4333-6853","authenticated-orcid":false,"given":"Aneta","family":"Jo\u0144czy","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology PAS, 28-130 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5869-7670","authenticated-orcid":false,"given":"Zuzanna","family":"Kope\u0107","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology PAS, 28-130 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2719-6205","authenticated-orcid":false,"given":"Adrian M.","family":"Stankiewicz","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology PAS, 28-130 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian","family":"Kamyczek","sequence":"additional","affiliation":[{"name":"Pig Hybridization Centre, National Research Institute of Animal Production, 43-246 Paw\u0142owice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1040-9446","authenticated-orcid":false,"given":"Dorine","family":"Swinkels","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine (TLM 830), Radboud University Nijmegen Medical Center, 6525 GA Nijmegen, The Netherlands"},{"name":"Hepcidin Analysis, Department of Laboratory Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"\u017belazowska","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology PAS, 28-130 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafa\u0142 R.","family":"Starzy\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Genetics and Animal Biotechnology PAS, 28-130 Jastrz\u0119biec, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"ref_1","first-page":"104","article-title":"Iron deficiency in suckling piglets: Etiology, clinical aspects and diagnosis","volume":"49","author":"Svoboda","year":"2005","journal-title":"Folia Vet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.anifeedsci.2017.11.001","article-title":"Iron status of piglets and impact of phytase superdosing on iron physiology: A review","volume":"235","author":"Kim","year":"2018","journal-title":"Anim. Feed Sci. Technol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Szudzik, M., Starzy\u0144ski, R.R., Jo\u0144czy, A., Mazgaj, R., Lenartowicz, M., and Lipi\u0144ski, P. (2018). Iron supplementation in suckling piglets: An ostensibly easy therapy of neonatal iron deficiency anemia. Pharmaceuticals, 11.","DOI":"10.20944\/preprints201810.0189.v1"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1053\/rvsc.1998.0223","article-title":"An evaluation of iron-dextran supplementation in piglets administered by injection on the first, third or fourth day after birth","volume":"66","author":"Egeli","year":"1999","journal-title":"Res. Vet. Sci."},{"key":"ref_5","first-page":"145","article-title":"Sudden death in suckling piglets following administration of iron-dextran-preparation","volume":"73","year":"1966","journal-title":"Dtsch. Tierarztl. Wochenschr."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Bloor, S.R., Schutte, R., and Hobson, A.R. (2021). Oral Iron Supplementation\u2014Gastrointestinal Side Effects and the Impact on the Gut Microbiota. Microbiol. Res., 12.","DOI":"10.3390\/microbiolres12020033"},{"key":"ref_7","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_8","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1046\/j.1439-0442.2002.00448.x","article-title":"Iron deficiency in outdoor pig production","volume":"49","author":"Szabo","year":"2002","journal-title":"J. Vet. Med. Ser. A Physiol. Pathol. Clin. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"77","DOI":"10.2754\/avb201887010077","article-title":"Oral iron administration in suckling piglets\u2014A review","volume":"87","author":"Svoboda","year":"2018","journal-title":"Acta Vet. Brno"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1136\/vr.c7033","article-title":"Comparison of oral versus parenteral iron supplementation on the health and productivity of piglets","volume":"168","author":"Maes","year":"2011","journal-title":"Vet. Rec."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1080\/09637480500085820","article-title":"Iron availability: An updated review","volume":"55","author":"Martos","year":"2004","journal-title":"Int. J. Food Sci. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.2353\/ajpath.2010.091020","article-title":"Benefits and Risks of Iron Supplementation in Anemic Neonatal Pigs","volume":"177","author":"Tudek","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1109\/TMAG.2010.2046907","article-title":"Biomedical Nanomagnetics: A Spin Through Possibilities in Imaging, Diagnostics, and Therapy","volume":"46","author":"Krishnan","year":"2010","journal-title":"IEEE Trans. Magn."},{"key":"ref_14","first-page":"1369","article-title":"Metal Nano Networks by Potential-Controlled In Situ Assembling of Gold\/Silver Nanoparticles","volume":"8","author":"Kluitmann","year":"2019","journal-title":"Chem. Open"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9615","DOI":"10.1016\/j.biomaterials.2013.08.025","article-title":"Suppressing iron oxide nanoparticle toxicity by vascular targeted antioxidant polymer nanoparticles","volume":"34","author":"Cochran","year":"2013","journal-title":"Biomaterials"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1016\/j.tiv.2013.09.006","article-title":"Impact of iron oxide nanoparticles on brain, heart, lung, liver and kidneys mitochondrial respiratory chain complexes activities and coupling","volume":"27","author":"Baratli","year":"2013","journal-title":"Toxicol. In Vitro"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"205101","DOI":"10.1088\/0957-4484\/26\/20\/205101","article-title":"Safety assessment of chronic oral exposure to iron oxide nanoparticles","volume":"26","author":"Chamorro","year":"2015","journal-title":"Nanotechnology"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"G\u00f3mez-Ram\u00edrez, S., Brilli, E., Tarantino, G., and Mu\u00f1oz, M. (2018). Sucrosomial\u00ae iron: A new generation iron for improving oral supplementation. Pharmaceuticals, 11.","DOI":"10.3390\/ph11040097"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4563","DOI":"10.1182\/blood.V126.23.4563.4563","article-title":"Innovative Oral Iron Supplement (Sucrosomial Iron\u00ae) Is Able to Downregulate Hepcidin Release during Inflammation: In Vitro Study","volume":"126","author":"Tarantino","year":"2015","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1007\/s12011-019-01950-w","article-title":"Long-term Effect of Split Iron Dextran\/Hemoglobin Supplementation on Erythrocyte and Iron Status, Growth Performance, Carcass Parameters, and Meat Quality of Polish Large White and 990 Line Pigs","volume":"196","author":"Szudzik","year":"2020","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mazgaj, R., Szudzik, M., Lipi\u0144ski, P., Jo\u0144czy, A., Smuda, E., Kamyczek, M., Cie\u015blak, B., Swinkels, D., Lenartowicz, M., and Starzy\u0144ski, R.R. (2020). Effect of Oral Supplementation of Healthy Pregnant Sows with Sucrosomial Ferric Pyrophosphate on Maternal Iron Status and Hepatic Iron Stores in Newborn Piglets. Animals, 10.","DOI":"10.3390\/ani10071113"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1080\/14767058.2016.1224841","article-title":"Effects of different regimens of iron prophylaxis on maternal iron status and pregnancy outcome: A randomized control trial","volume":"30","author":"Parisi","year":"2017","journal-title":"J. Matern. Neonatal Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/prca.201300099","article-title":"The pig as an animal model for human pathologies: A proteomics perspective","volume":"8","author":"Bassols","year":"2014","journal-title":"Proteomics Clin. Appl."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1186\/BF03547786","article-title":"Clinical Biochemistry, Haematology and Body Weight in Piglets","volume":"39","author":"Egeli","year":"1998","journal-title":"Acta Vet. Scand."},{"key":"ref_25","first-page":"1","article-title":"The biomedical piglet: Establishing reference intervals for haematology and clinical chemistry parameters of two age groups with and without iron supplementation","volume":"13","author":"Ventrella","year":"2017","journal-title":"BMC Vet. Res."},{"key":"ref_26","first-page":"53","article-title":"The Use of Fecal Calprotectin in Inflammatory Bowel Disease","volume":"13","author":"Bjarnason","year":"2017","journal-title":"Gastroenterol. Hepatol."},{"key":"ref_27","first-page":"549","article-title":"Faecal Calprotectin\u2014An Objective Measure of Disease Activity in Childhood Inflammatory Bowel Disease","volume":"28","author":"Bunn","year":"1999","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1042\/bj3500589","article-title":"Fetuin-B, a second member of the fetuin family in mammals","volume":"350","author":"Olivier","year":"2000","journal-title":"Biochem. J."},{"key":"ref_29","first-page":"1105","article-title":"Mildly elevated liver transaminase levels in the asymptomatic patient","volume":"71","author":"Giboney","year":"2005","journal-title":"Am. Fam. Physician"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.biomaterials.2010.08.110","article-title":"Acute phase proteins as biomarkers for predicting the exposure and toxicity of nanomaterials","volume":"32","author":"Higashisaka","year":"2011","journal-title":"Biomaterials"},{"key":"ref_31","first-page":"958","article-title":"Potential of acute-phase proteins as biomarkers for sub-nano platinum exposure","volume":"67","author":"Nagano","year":"2012","journal-title":"Pharmazie"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.cell.2016.12.034","article-title":"A Red Carpet for Iron Metabolism","volume":"168","author":"Muckenthaler","year":"2017","journal-title":"Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s00018-012-1018-1","article-title":"Molecular insights into the regulation of iron metabolism during the prenatal and early postnatal periods","volume":"70","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_34","first-page":"1","article-title":"Urinary hepcidin levels in iron-deficient and iron-supplemented piglets correlate with hepcidin hepatic mRNA and serum levels and with body iron status","volume":"10","author":"Gajowiak","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0181117","article-title":"Dietary hemoglobin rescues young piglets from severe iron deficiency anemia: Duodenal expression profile of genes involved in heme iron absorption","volume":"12","author":"Staron","year":"2017","journal-title":"PLoS ONE"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1126\/science.aau6481","article-title":"Dendritic cell\u2013derived hepcidin sequesters iron from the microbiota to promote mucosal healing","volume":"368","author":"Bessman","year":"2020","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.2527\/jas.2007-0577","article-title":"Effects of neonatal iron status, iron injections at birth, and weaning in young pigs from sows fed either organic or inorganic trace minerals","volume":"86","author":"Peters","year":"2008","journal-title":"J. Anim. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"G397","DOI":"10.1152\/ajpgi.00348.2013","article-title":"Mechanistic and regulatory aspects of intestinal iron absorption","volume":"307","author":"Gulec","year":"2014","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/978-1-59745-210-6_10","article-title":"pH-Responsive Nanoparticles for Cancer Drug Delivery","volume":"Volume 437","author":"Shen","year":"2008","journal-title":"Methods in Molecular Biology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.jmmm.2005.01.064","article-title":"Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system","volume":"293","author":"Neuberger","year":"2005","journal-title":"J. Magn. Magn. Mater."},{"key":"ref_41","first-page":"203","article-title":"A review on techniques for oral bioavailability enhancement of drugs","volume":"4","author":"Thakkar","year":"2010","journal-title":"Int. J. Pharm. Sci. Rev. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1038\/nnano.2010.79","article-title":"Iron from nanocompounds containing iron and zinc is highly bioavailable in rats without tissue accumulation","volume":"5","author":"Hilty","year":"2010","journal-title":"Nat. Nanotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3","DOI":"10.15171\/apb.2017.002","article-title":"Application of Various Types of Liposomes in Drug Delivery Systems","volume":"7","author":"Alavi","year":"2017","journal-title":"Adv. Pharm. Bull."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1024\/0300-9831.74.6.453","article-title":"The potential of encapsulated iron compounds in food fortification: A review","volume":"74","author":"Zimmermann","year":"2004","journal-title":"Int. J. Vitam. Nutr. Res."},{"key":"ref_45","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_46","doi-asserted-by":"crossref","unstructured":"Churio, O., Dur\u00e1n, E., Guzm\u00e1n-Pino, S.A., and Valenzuela, C. (2019). Use of encapsulation technology to improve the efficiency of an iron oral supplement to prevent anemia in suckling pigs. Animals, 9.","DOI":"10.3390\/ani9010001"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3301","DOI":"10.1093\/jn\/134.12.3301","article-title":"Particle Size Reduction and Encapsulation Affect the Bioavailability of Ferric Pyrophosphate in Rats","volume":"134","author":"Zimmermann","year":"2004","journal-title":"J. Nutr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"117","DOI":"10.4103\/2008-7802.193092","article-title":"The effects of nanoparticles containing iron on blood and inflammatory markers in comparison to ferrous sulfate in anemic rats","volume":"7","author":"Shafie","year":"2016","journal-title":"Int. J. Prev. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/287575","article-title":"Treatment of Anemia Progression via Magnetite and Folate Nanoparticles In Vivo","volume":"2014","author":"Elsayed","year":"2014","journal-title":"ISRN Nanotechnol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"216","DOI":"10.5187\/jast.2019.61.4.216","article-title":"Effects of hot melt extrusion processed nano-iron on growth performance, blood composition, and iron bioavailability in weanling pigs","volume":"61","author":"Lee","year":"2019","journal-title":"J. Anim. Sci. Technol."},{"key":"ref_51","first-page":"1439","article-title":"Structure\/histotoxicity relationship of parenteral iron preparations","volume":"42","author":"Geisser","year":"1992","journal-title":"Arzneimittelforschung"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Rausa, M., Pagani, A., Nai, A., Campanella, A., Gilberti, M.E., Apostoli, P., Camaschella, C., and Silvestri, L. (2015). Bmp6 Expression in Murine Liver Non Parenchymal Cells: A Mechanism to Control their High Iron Exporter Activity and Protect Hepatocytes from Iron Overload?. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122696"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7811","DOI":"10.1074\/jbc.M008923200","article-title":"A New Mouse Liver-specific Gene, Encoding a Protein Homologous to Human Antimicrobial Peptide Hepcidin, Is Overexpressed during Iron Overload","volume":"276","author":"Pigeon","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1182\/blood-2007-04-087593","article-title":"Iron transferrin regulates hepcidin synthesis in primary hepatocyte culture through hemojuvelin and BMP2\/4","volume":"110","author":"Lin","year":"2007","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1182\/bloodadvances.2020003632","article-title":"Dynamic changes in murine erythropoiesis from birth to adulthood: Implications for the study of murine models of anemia","volume":"5","author":"Chen","year":"2021","journal-title":"Blood Adv."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1002\/iub.1629","article-title":"Systemic iron homeostasis and erythropoiesis","volume":"69","author":"Papanikolaou","year":"2017","journal-title":"IUBMB Life"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1053\/j.ajkd.2010.03.025","article-title":"Hemolysis and acute kidney failure","volume":"56","author":"Qian","year":"2010","journal-title":"Am. J. Kidney Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3832","DOI":"10.1016\/j.actbio.2012.06.029","article-title":"Ferritin up-regulation and transient ROS production in cultured brain astrocytes after loading with iron oxide nanoparticles","volume":"8","author":"Geppert","year":"2012","journal-title":"Acta Biomater."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3988","DOI":"10.1016\/j.biomaterials.2011.02.031","article-title":"Long term in vivo biotransformation of iron oxide nanoparticles","volume":"32","author":"Levy","year":"2011","journal-title":"Biomaterials"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1007\/s12020-017-1417-z","article-title":"Association of fetuin B with markers of liver fibrosis in nonalcoholic fatty liver disease","volume":"58","author":"Ebert","year":"2017","journal-title":"Endocrine"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.tox.2010.06.002","article-title":"Inflammatory responses may be induced by a single intratracheal instillation of iron nanoparticles in mice","volume":"275","author":"Park","year":"2010","journal-title":"Toxicology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1089\/104454902753759717","article-title":"Hemopexin: Structure, Function, and Regulation","volume":"21","author":"Tolosano","year":"2002","journal-title":"DNA Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Fabiano, A., Brilli, E., Mattii, L., Testai, L., Moscato, S., Citi, V., Tarantino, G., and Zambito, Y. (2018). Ex vivo and in vivo study of sucrosomial\u00ae iron intestinal absorption and bioavailability. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19092722"},{"key":"ref_64","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_65","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/mi.2013.30","article-title":"Microfold (M) cells: Important immunosurveillance posts in the intestinal epithelium","volume":"6","author":"Mabbott","year":"2013","journal-title":"Mucosal Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"111814","DOI":"10.1016\/j.fct.2020.111814","article-title":"Food additives containing nanoparticles induce gastrotoxicity, hepatotoxicity and alterations in animal behavior: The unknown role of oxidative stress","volume":"146","author":"Chirino","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1186\/s40168-017-0268-4","article-title":"A critical assessment of the \u201csterile womb\u201d and \u201cin utero colonization\u201d hypotheses: Implications for research on the pioneer infant microbiome","volume":"5","author":"Arrieta","year":"2017","journal-title":"Microbiome"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40168-015-0091-8","article-title":"Diet shapes the gut microbiome of pigs during nursing and weaning","volume":"3","author":"Frese","year":"2015","journal-title":"Microbiome"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1111\/1758-2229.12285","article-title":"Early-life establishment of the swine gut microbiome and impact on host phenotypes","volume":"7","author":"Mach","year":"2015","journal-title":"Environ. Microbiol. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"6012","DOI":"10.1038\/s41598-018-24508-7","article-title":"Tracing of the fecal microbiota of commercial pigs at five growth stages from birth to shipment","volume":"8","author":"Han","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Mariat, D., Firmesse, O., Levenez, F., Guimar\u0103es, V., Sokol, H., Dor\u00e9, J., Corthier, G., and Furet, J.-P. (2009). The Firmicutes\/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol., 9.","DOI":"10.1186\/1471-2180-9-123"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/j.1600-0609.1981.tb01379.x","article-title":"The Relationship between Maternal and Infant Iron Status","volume":"25","author":"Macphail","year":"1981","journal-title":"Scand. J. Haematol."},{"key":"ref_73","first-page":"1","article-title":"Iron Supplementation in Suckling Piglets: How to Correct Iron Deficiency Anemia without Affecting Plasma Hepcidin Levels","volume":"8","author":"Laarakkers","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Laarakkers, C.M.M., Wiegerinck, E.T., Klaver, S., Kolodziejczyk, M., Gille, H., Hohlbaum, A.M., Tjalsma, H., and Swinkels, D.W. (2013). Improved Mass Spectrometry Assay For Plasma Hepcidin: Detection and Characterization of a Novel Hepcidin Isoform. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0075518"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5245","DOI":"10.1158\/0008-5472.CAN-04-0496","article-title":"Normalization of Real-Time Quantitative Reverse Transcription-PCR Data: A Model-Based Variance Estimation Approach to Identify Genes Suited for Normalization, Applied to Bladder and Colon Cancer Data Sets","volume":"64","author":"Andersen","year":"2004","journal-title":"Cancer Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4406","DOI":"10.1182\/blood.V93.12.4406","article-title":"Cellular and Subcellular Localization of the Nramp2 Iron Transporter in the Intestinal Brush Border and Regulation by Dietary Iron","volume":"93","author":"Gruenheid","year":"1999","journal-title":"Blood"},{"key":"ref_77","first-page":"3964","article-title":"The Nramp2\/DMT1 iron transporter is induced in the duodenum of microcytic anemia mk mice but is not properly targeted to the intestinal brush border","volume":"96","author":"Fleming","year":"2000","journal-title":"Blood"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/0891-5849(93)90035-S","article-title":"A comparative evaluation of thiobarbituric acid methods for the determination of malondialdehyde in biological materials","volume":"15","author":"Draper","year":"1993","journal-title":"Free Radic. Biol. Med."},{"key":"ref_79","unstructured":"Rstudio T (2021, August 11). RStudio: Integrated Development for R. Available online: http\/\/www.rstudio.com."},{"key":"ref_80","unstructured":"CoreTeam, R. (2017). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the Tidyverse","volume":"4","author":"Wickham","year":"2019","journal-title":"J. Open Source Softw."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Ma, S., Shungin, D., Mallick, H., Schirmer, M., Nguyen, L.H., Kolde, R., Franzosa, E., Vlamakis, H., Xavier, R., and Huttenhower, C. (2020). Population Structure Discovery in Meta-Analyzed Microbial Communities and Inflammatory Bowel Disease. bioRxiv.","DOI":"10.1101\/2020.08.31.261214"},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Willis, A.D., and Martin, B.D. (2020). Estimating diversity in networked ecological communities. Biostatistics, 1\u201323.","DOI":"10.1093\/biostatistics\/kxaa015"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1111\/rssc.12206","article-title":"Improved detection of changes in species richness in high diversity microbial communities","volume":"66","author":"Willis","year":"2017","journal-title":"J. R. Stat. Soc. Ser. C"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1042","DOI":"10.1111\/biom.12332","article-title":"Estimating diversity via frequency ratios","volume":"71","author":"Willis","year":"2015","journal-title":"Biometrics"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/mSystems.00016-19","article-title":"A Novel Sparse Compositional Technique Reveals Microbial Perturbations","volume":"4","author":"Martino","year":"2019","journal-title":"mSystems"},{"key":"ref_87","first-page":"5","article-title":"vegan: Community Ecology Package. R package version 2.4-2","volume":"2","author":"Oksanen","year":"2019","journal-title":"Community Ecol. Package"},{"key":"ref_88","unstructured":"Martinez Arbizu, P. (2021, August 11). pairwiseAdonis: Pairwise multilevel comparison using adonis. R Package Version 0.0 2017. Available online: https:\/\/github.com\/pmartinezarbizu\/pairwiseAdonis."},{"key":"ref_89","unstructured":"De Vries, A., and Ripley, B.D. (2021, August 11). Package \u201cggdendro\u201d: Create Dendrograms and Tree Diagrams Using \u201cggplot2\u201d. R Package Version 0.1-20 2016. Available online: https:\/\/cran.r-project.org\/web\/packages\/ggdendro\/index.html."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s40168-017-0237-y","article-title":"Normalization and microbial differential abundance strategies depend upon data characteristics","volume":"5","author":"Weiss","year":"2017","journal-title":"Microbiome"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9930\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:02:37Z","timestamp":1760166157000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9930"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,14]]},"references-count":92,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22189930"],"URL":"https:\/\/doi.org\/10.3390\/ijms22189930","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,14]]}}}