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Impaired Iron-Copper Metabolic Axis in Human Intestinal Mucosa After Roux-en-Y Gastric Bypass: A Prospective

Camila Shimizu1, Dan Linetzky Waitzberg2, Raquel Susana Torrinhas2

  • 1Curso de Nutrição, Centro Universitário São Camilo, São Paulo, Brazil.

Obesity Surgery
|May 8, 2026
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Summary

Roux-en-Y gastric bypass (RYGB) alters intestinal gene expression, upregulating iron transporter DMT1 and downregulating copper-related genes CP and LOX. These changes may explain post-surgery micronutrient deficiencies.

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Area of Science:

  • Gastroenterology
  • Molecular Biology
  • Nutritional Science

Background:

  • Roux-en-Y gastric bypass (RYGB) is effective for severe obesity but often causes iron deficiency.
  • The intestinal mechanisms of copper-iron metabolism after RYGB are not well understood.
  • This study investigates RYGB's impact on intestinal gene expression related to nutrient homeostasis.

Purpose of the Study:

  • To evaluate the longitudinal changes in intestinal gene expression post-RYGB.
  • To understand the molecular adaptations in micronutrient homeostasis after bariatric surgery.
  • To explore the impact of RYGB on the copper-iron metabolic axis in the human intestine.

Main Methods:

  • Prospective study of 20 women undergoing RYGB.
  • Intestinal biopsies collected via double-balloon enteroscopy (DBE) pre- and 3 months post-surgery.
  • Gene expression analysis using microarrays and RT-qPCR for Ceruloplasmin (CP).

Main Results:

  • Significant BMI reduction post-RYGB.
  • Segment-specific gene expression changes observed.
  • Upregulation of Divalent Metal Transporter 1 (DMT1) in the bypassed duodenum.
  • Downregulation of Ceruloplasmin (CP) and Lysyl Oxidase (LOX) across intestinal segments.

Conclusions:

  • RYGB induces early, segment-specific transcriptional changes in the intestinal mucosa.
  • DMT1 upregulation suggests a compensatory response to reduced iron availability.
  • CP and LOX downregulation indicates potential alterations in the copper-iron axis, contributing to micronutrient issues.