title: Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities.
abstract: Surgical interposition of distal ileum into the proximal jejunum is a bariatric procedure that improves the metabolic syndrome. Changes in intestinal and hepatic physiology after ileal interposition (transposition) surgery (IIS) are not well understood. Our aim was to elucidate the adaptation of the interposed ileum, which we hypothesized, would lead to early bile acid reabsorption in the interposed ileum, thus short circuiting enterohepatic bile acid recycling to more proximal bowel segments. Rats with diet-induced obesity were randomized to IIS, with 10 cm of ileum repositioned distal to the duodenum, or sham surgery. A subgroup of sham rats was pair-fed to IIS rats. Physiological parameters were measured until 6 wk postsurgery. IIS rats ate less and lost more weight for the first 2 wk postsurgery. At study completion, body weights were not different, but IIS rats had reversed components of the metabolic syndrome. The interposed ileal segment adapted to a more jejunum-like villi length, mucosal surface area, and GATA4/ILBP mRNA. The interposed segment retained capacity for bile acid reabsorption and anorectic hormone secretion with the presence of ASBT and glucagon-like-peptide-1-positive cells in the villi. IIS rats had reduced primary bile acid levels in the proximal intestinal tract and higher primary bile acid levels in the serum, suggesting an early and efficient reabsorption of primary bile acids. IIS rats also had increased taurine and glycine-conjugated serum bile acids and reduced fecal bile acid loss. There was decreased hepatic Cyp27A1 mRNA with no changes in hepatic FXR, SHP, or NTCP expression. IIS protects against the metabolic syndrome through short-circuiting enterohepatic bile acid recycling. There is early reabsorption of primary bile acids despite selective "jejunization" of the interposed ileal segment. Changes in serum bile acids or bile acid enterohepatic recycling may mediate the metabolic benefits seen after bariatric surgery.
authors.affiliation: Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Ohio, USA. rohit.kohli@cchmc.org
authors.forename: Rohit
authors.initials: R
authors.lastname: Kohli
authors.forename: Michelle
authors.initials: M
authors.lastname: Kirby
authors.forename: Kenneth D R
authors.initials: KD
authors.lastname: Setchell
authors.forename: Pinky
authors.initials: P
authors.lastname: Jha
authors.forename: Kori
authors.initials: K
authors.lastname: Klustaitis
authors.forename: Laura A
authors.initials: LA
authors.lastname: Woollett
authors.forename: Paul T
authors.initials: PT
authors.lastname: Pfluger
authors.forename: William F
authors.initials: WF
authors.lastname: Balistreri
authors.forename: Patrick
authors.initials: P
authors.lastname: Tso
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Jandacek
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
authors.forename: James E
authors.initials: JE
authors.lastname: Heubi
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschoep
authors.forename: David A
authors.initials: DA
authors.lastname: D'Alessio
authors.forename: Noah F
authors.initials: NF
authors.lastname: Shroyer
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Seeley
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001647:Bile Acids and Salts / Q000032:analysis / Q000378:metabolism*; D053493:Cholestanetriol 26-Monooxygenase / Q000235:genetics / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D005766:Gastrointestinal Contents / Q000737:chemistry; D005786:Gene Expression Regulation / Q000502:physiology; D007082:Ileum / Q000473:pathology / Q000502:physiology / Q000601:surgery*; D008297:Male; D009765:Obesity / Q000150:complications*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D001647:Bile Acids and Salts; D012333:RNA, Messenger; D053493:Cholestanetriol 26-Monooxygenase