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Diabetes-associated microbiota in fa/fa rats is modified by Roux-en-Y gastric bypass

Journal article
Authors Tulika Arora
F. Seyfried
Neil G. Docherty
Valentina Tremaroli
Carel W le Roux
Rosie Perkins
Fredrik Bäckhed
Published in Isme Journal
Volume 11
Issue 9
Pages 2035-2046
ISSN 1751-7362
Publication year 2017
Published at Wallenberg Laboratory
Institute of Clinical Sciences, Section for Surgery and Gastrosurgical Research and Education, Department of Gastrosurgical Research and Education
Institute of Medicine, Department of Molecular and Clinical Medicine
Pages 2035-2046
Language English
Links doi.org/10.1038/ismej.2017.70
Keywords HUMAN GUT MICROBIOME, OBESE ZUCKER RAT, BARIATRIC SURGERY, FATTY RATS, METABOLIC PARAMETERS, GLUCOSE-HOMEOSTASIS, INSULIN SENSITIVITY, GLYCEMIC, CONTROL, SMALL-INTESTINE, WEIGHT-LOSS
Subject categories Surgery, Gastroenterology and Hepatology, Endocrinology and Diabetes

Abstract

Roux-en-Y gastric bypass (RYGB) and duodenal jejunal bypass (DJB), two different forms of bariatric surgery, are associated with improved glucose tolerance, but it is not clear whether the gut microbiota contributes to this effect. Here we used fa/fa rats as a model of impaired glucose tolerance to investigate whether (i) the microbiota varies between fa/fa and nondiabetic fa/+ rats; (ii) the microbiota of fa/fa rats is affected by RYGB and/or DJB; and (iii) surgically induced microbiota alterations contribute to glucose metabolism. We observed a profound expansion of Firmicutes (specifically, Lactobacillus animalis and Lactobacillus reuteri) in the small intestine of diabetic fa/fa compared with nondiabetic fa/+ rats. RYGB-, but not DJB-, treated fa/fa rats exhibited greater microbiota diversity in the ileum and lower L. animalis and L. reuteri abundance compared with shamoperated fa/fa rats in all intestinal segments, and their microbiota composition resembled that of unoperated fa/+ rats. To investigate the functional role of RYGB-associated microbiota alterations, we transferred microbiota from sham-and RYGB-treated fa/fa rats to germ-free mice. The metabolic phenotype of RYGB-treated rats was not transferred by the transplant of ileal microbiota. In contrast, postprandial peak glucose levels were lower in mice that received cecal microbiota from RYGBversus sham-operated rats. Thus, diabetes-associated microbiota alterations in fa/fa rats can be modified by RYGB, and modifications in the cecal microbiota may partially contribute to improved glucose tolerance after RYGB.

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