title: Gastrointestinal Transcriptomic Response of Metabolic Vitamin B12 Pathways in Roux-en-Y Gastric Bypass.
abstract: OBJECTIVE
  Vitamin B12 (B12) deficiency after Roux-en-Y gastric bypass (RYGB) is highly prevalent and may contribute to postoperative complications. Decreased production of intrinsic factor owing to gastric fundus removal is thought to have a major role, but other components of B12 metabolism may also be affected. We evaluated changes in the expression levels of multiple B12 pathway-encoding genes in gastrointestinal (GI) tissues to evaluate the potential roles in contributing to post-RYGB B12 deficiency.
  
  
  METHODS
  During double-balloon enteroscopy, serial GI biopsies were collected from 20 obese women (age, 46.9±6.2 years; body mass index, 46.5±5.3 kg/m2) with adult-onset type 2 diabetes (fasting plasma glucose ≥126 mg/dl; hemoglobin A1c≥6.5%) before and, at the same site, 3 months after RYGB. Gene expression levels were assessed by the Affymetrix Human GeneChip 1.0 ST microarray. Findings were validated by real-time quantitative PCR (RT-qPCR).
  
  
  RESULTS
  Gene expression levels with significant changes (P≤0.05) included: transcobalamin I (TCN1) in remnant (-1.914-fold) and excluded (-1.985-fold) gastric regions; gastric intrinsic factor (GIF) in duodenum (-0.725-fold); and cubilin (CUBN) in duodenum (+0.982-fold), jejunum (+1.311-fold), and ileum (+0.685-fold). Validation by RT-qPCR confirmed (P≤0.05) observed changes for TCN1 in the remnant gastric region (-0.132-fold) and CUBN in jejunum (+2.833-fold).
  
  
  CONCLUSIONS
  RYGB affects multiple pathway-encoding genes that may be associated with postoperative B12 deficiency. Decreased TCN1 levels seem to be the main contributing factor. Increased CUBN levels suggest an adaptive genetic reprogramming of intestinal tissue aiming to compensate for impaired intestinal B12 delivery.
authors.affiliation: FMUSP-Department of Gastroenterology, Digestive Surgery Discipline, School of Medicine, University of São Paulo (LIM 35), São Paulo, Brazil.
authors.forename: Priscila
authors.initials: P
authors.lastname: Sala
authors.affiliation: FMUSP-Department of Gastroenterology, Digestive Surgery Discipline, School of Medicine, University of São Paulo (LIM 35), São Paulo, Brazil.
authors.forename: Giliane
authors.initials: G
authors.lastname: Belarmino
authors.affiliation: FMUSP-Department of Gastroenterology, Digestive Surgery Discipline, School of Medicine, University of São Paulo (LIM 35), São Paulo, Brazil.
authors.forename: Raquel S
authors.initials: RS
authors.lastname: Torrinhas
authors.affiliation: FMUSP-Department of Gastroenterology, Digestive Surgery Discipline, School of Medicine, University of São Paulo (LIM 35), São Paulo, Brazil.
authors.forename: Natasha M
authors.initials: NM
authors.lastname: Machado
authors.affiliation: FMUSP-Department of Gastroenterology, Digestive Surgery Discipline, School of Medicine, University of São Paulo (LIM 35), São Paulo, Brazil.
authors.forename: Danielle C
authors.initials: DC
authors.lastname: Fonseca
authors.affiliation: FMUSP-Department of Gastroenterology, Digestive Surgery Discipline, School of Medicine, University of São Paulo (LIM 35), São Paulo, Brazil.
authors.forename: Graziela R
authors.initials: GR
authors.lastname: Ravacci
authors.affiliation: FMUSP-Department of Gastroenterology, Digestive Surgery Discipline, School of Medicine, University of São Paulo (LIM 35), São Paulo, Brazil.
authors.forename: Robson K
authors.initials: RK
authors.lastname: Ishida
authors.affiliation: FMUSP-Department of Gastroenterology, Digestive Surgery Discipline, School of Medicine, University of São Paulo (LIM 35), São Paulo, Brazil.
authors.forename: Ismael F M S
authors.initials: IF
authors.lastname: Guarda
authors.affiliation: FMUSP-Department of Gastroenterology, Digestive Surgery Discipline, School of Medicine, University of São Paulo (LIM 35), São Paulo, Brazil.
authors.forename: Eduardo G
authors.initials: EG
authors.lastname: de Moura
authors.affiliation: FMUSP-Department of Gastroenterology, Digestive Surgery Discipline, School of Medicine, University of São Paulo (LIM 35), São Paulo, Brazil.
authors.forename: Paulo
authors.initials: P
authors.lastname: Sakai
authors.affiliation: FMUSP-Department of Gastroenterology, Digestive Surgery Discipline, School of Medicine, University of São Paulo (LIM 35), São Paulo, Brazil.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Santo
authors.affiliation: UNIFESP-Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Ismael D C G
authors.initials: ID
authors.lastname: da Silva
authors.affiliation: UNIFESP-Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Claudia C A
authors.initials: CC
authors.lastname: Pereira
authors.affiliation: UNIFESP-Federal University of São Paulo, São Paulo, Brazil.
authors.forename: Angela F
authors.initials: AF
authors.lastname: Logullo
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: Steven
authors.initials: S
authors.lastname: Heymsfield
authors.affiliation: University Nove de Julho, São Paulo, Brazil.
authors.forename: Daniel
authors.initials: D
authors.lastname: Giannella-Neto
authors.affiliation: FMUSP-Department of Gastroenterology, Digestive Surgery Discipline, School of Medicine, University of São Paulo (LIM 35), São Paulo, Brazil.
authors.forename: Dan L
authors.initials: DL
authors.lastname: Waitzberg