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Nat Commun. 2015 Jul 21;6:7715. doi: 10.1038/ncomms8715.

Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery.

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Department of Surgery, Vanderbilt University Medical Center, 1161 21st Avenue South, MCN CC2308, Nashville, Tennessee 37232-2730, USA.
Rosalind Franklin University, North Chicago, Illinois 60064, USA.
Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235-1634, USA.
Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, Tennessee 37232-2561, USA.
Center for Quantitative Sciences, Department of Cancer Biology, Vanderbilt University, Nashville, Tennessee 37232-6848, USA.
Department of Molecular Physiology &Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6303, USA.


Roux-en-Y gastric bypass (RYGB) is highly effective in reversing obesity and associated diabetes. Recent observations in humans suggest a contributing role of increased circulating bile acids in mediating such effects. Here we use a diet-induced obesity (DIO) mouse model and compare metabolic remission when bile flow is diverted through a gallbladder anastomosis to jejunum, ileum or duodenum (sham control). We find that only bile diversion to the ileum results in physiologic changes similar to RYGB, including sustained improvements in weight, glucose tolerance and hepatic steatosis despite differential effects on hepatic gene expression. Circulating free fatty acids and triglycerides decrease while bile acids increase, particularly conjugated tauro-β-muricholic acid, an FXR antagonist. Activity of the hepatic FXR/FGF15 signalling axis is reduced and associated with altered gut microbiota. Thus bile diversion, independent of surgical rearrangement of the gastrointestinal tract, imparts significant weight loss accompanied by improved glucose and lipid homeostasis that are hallmarks of RYGB.

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