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Iron deficiency is the most common nutrient disorder worldwide, and iron dysregulation in early life has been found to cause long-lasting behavioral, cognitive, and neural effects. However, little is known about the effects of dietary iron on gut microbiome function and metabolism. In this study, we sought to investigate the impact of dietary iron on the fecal metabolome and microbiome by using mice fed with three diets with different iron content: an iron deficient, an iron sufficient (standard), and an iron overload diet for 7 weeks. Additionally, we sought to understand whether any observed changes would persist past the 7-week period of diet intervention. To assess this, all feeding groups were switched to a standard diet, and this feeding continued for an additional 7 weeks. Analysis of the fecal metabolome revealed that iron overload and deficiency significantly alter levels of peptides, nucleic acids, and lipids, including di- and tri-peptides containing branched-chain amino acids, inosine and guanosine, and several microbial conjugated bile acids. The observed changes in the fecal metabolome persist long after the switch back to a standard diet, with the cecal gut microbiota composition and function of each group distinct after the 7-week standard diet wash-out. Our results highlight the enduring metabolic consequences of nutritional imbalances, mediated by both the host and gut microbiome, which persist after returning to the original standard diets.<\/jats:p>","DOI":"10.1093\/mtomcs\/mfae033","type":"journal-article","created":{"date-parts":[[2024,7,11]],"date-time":"2024-07-11T23:03:02Z","timestamp":1720738982000},"source":"Crossref","is-referenced-by-count":6,"title":["Dietary iron intake has long-term effects on the fecal metabolome and microbiome"],"prefix":"10.1093","volume":"16","author":[{"given":"Anastasiia","family":"Kostenko","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Denver , Denver, CO ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7237-3402","authenticated-orcid":false,"given":"Simone","family":"Zuffa","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego , San Diego, CA ,","place":["USA"]},{"name":"Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego , La Jolla, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zhi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Diego , La Jolla, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7776-0890","authenticated-orcid":false,"given":"Kevin","family":"Mildau","sequence":"additional","affiliation":[{"name":"Department of Analytical Chemistry, University of Vienna , Vienna ,","place":["Austria"]},{"name":"Bioinformatics Group, Wageningen University & Research , Wageningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6487-4215","authenticated-orcid":false,"given":"Manuela","family":"Raffatellu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of California San Diego , La Jolla, CA ,","place":["USA"]},{"name":"Chiba University, UC San Diego Center for Mucosal Immunology, Allergy, and Vaccines (CU-UCSD cMAV) , La Jolla, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter C","family":"Dorrestein","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego , San Diego, CA ,","place":["USA"]},{"name":"Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego , La Jolla, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9596-021X","authenticated-orcid":false,"given":"Allegra T","family":"Aron","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Denver , Denver, CO ,","place":["USA"]},{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego , San Diego, CA ,","place":["USA"]},{"name":"Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego , La Jolla, CA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,7,11]]},"reference":[{"issue":"4","key":"2026041420235257500_bib1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.blre.2017.02.004","article-title":"New insights into iron deficiency and iron deficiency anemia","volume":"31","author":"Camaschella","year":"2017","journal-title":"Blood Rev."},{"issue":"7","key":"2026041420235257500_bib2","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.3390\/nu12071993","article-title":"Iron supplementation influence on the gut microbiota and probiotic intake effect in Iron deficiency\u2014a literature-based review","volume":"12","author":"Rusu","year":"2020","journal-title":"Nutrients"},{"issue":"6","key":"2026041420235257500_bib3","doi-asserted-by":"crossref","first-page":"e2021055926","DOI":"10.1542\/peds.2021-055926","article-title":"Chronic iron deficiency and cognitive function in early childhood","volume":"150","author":"Gingoyon","year":"2022","journal-title":"Pediatrics"},{"key":"2026041420235257500_bib4","first-page":"253","article-title":"Iron and prebiotic fortified flour improves the immune function of iron deficient women of childbearing age","volume":"33","author":"Rizwan Ahmad","year":"2020","journal-title":"Pak. 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