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The molecular mechanisms governing the human intestinal copper-iron metabolic axis post-surgery remain poorly defined. This study evaluated the longitudinal impact of RYGB on intestinal gene expression related to micronutrient homeostasis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a prospective study of 20 women (body mass index, BMI 46.5\u2009\u00b1\u20095.3\u00a0kg\/m\u00b2), intestinal mucosa biopsies were collected via double-balloon enteroscopy (DBE) pre- and three months post-RYGB from anatomically marked sites in the duodenum, jejunum, and ileum. Gene expression was assessed using Affymetrix microarrays, with Ceruloplasmin (CP) validated by RT-qPCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three months post-RYGB, BMI significantly (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) decreased to 38.2\u2009\u00b1\u20094.2\u00a0kg\/m\u00b2. Microarray analysis revealed segment-specific adaptations. Divalent metal transporter 1 (DMT1) was significantly (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) upregulated in the bypassed duodenum (+\u20090.421), indicating a local compensatory response to decreased iron availability. Conversely, CP expression was significantly downregulated across all segments, notably in the jejunum (\u2212\u20091.017;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). This downregulation, confirmed by RT-qPCR, suggests impaired iron oxidation and mobilization. Lysyl oxidase (LOX), a copper-dependent enzyme critical for mucosal structural integrity, was also significantly downregulated in the duodenum (\u2212\u20090.333;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) and jejunum (\u2212\u20090.450;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>RYGB induces early and segment-specific transcriptional adaptations in the intestinal mucosa. The upregulation of DMT1 in the bypassed duodenum suggests a compensatory response, whereas the consistent downregulation of CP and LOX indicates a potential alteration in the copper\u2013iron metabolic axis. These findings provide a biologically plausible framework for postoperative micronutrient disturbances; however, in the absence of functional and biochemical data, causal relationships cannot be established.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11695-026-08713-2","type":"journal-article","created":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:25:39Z","timestamp":1778286339000},"page":"3071-3077","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impaired Iron-Copper Metabolic Axis in Human Intestinal Mucosa After Roux-en-Y Gastric Bypass: A Prospective Transcriptomic Study Using Double-Balloon Enteroscopy"],"prefix":"10.1007","volume":"36","author":[{"given":"Camila","family":"Shimizu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan Linetzky","family":"Waitzberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel Susana","family":"Torrinhas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven B.","family":"Heymsfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Doce","family":"Passadore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila","family":"Sala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,9]]},"reference":[{"key":"8713_CR1","unstructured":"1. 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