Article Text

Original research
Human gut microbiota after bariatric surgery alters intestinal morphology and glucose absorption in mice independently of obesity
  1. Fernando F Anhê1,
  2. Soumaya Zlitni2,
  3. Song-Yang Zhang3,
  4. Béatrice So-Yun Choi4,
  5. Cassandra Y Chen1,
  6. Kevin P Foley1,
  7. Nicole G Barra1,
  8. Michael G Surette5,
  9. Laurent Biertho4,
  10. Denis Richard4,
  11. André Tchernof4,6,
  12. Tony K T Lam3,
  13. Andre Marette4,
  14. Jonathan Schertzer1
  1. 1Department of Biochemistry and Biomedical Sciences, Farncombe Family Digestive Health Research Institute, and Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada
  2. 2Department of Genetics and Medicine, Stanford University, Stanford, California, USA
  3. 3Toronto General Hospital Research Institute, University Health Network, Toronto, Ontario, Canada
  4. 4Quebec Heart and Lung Institute Research Centre, Laval University, Quebec, Quebec, Canada
  5. 5Department of Medicine, Farncombe Family Digestive Health Research Institute, and Centre for Metabolism, Obesity and Diabetes Research, McMaster University, Hamilton, Ontario, Canada
  6. 6School of Nutrition, Laval University, Quebec, Quebec, Canada
  1. Correspondence to Dr Jonathan Schertzer, Department of Biochemistry and Biomedical Sciences, Hamilton, Hamilton, Canada; schertze{at}mcmaster.ca

Abstract

Objective Bariatric surgery is an effective treatment for type 2 diabetes (T2D) that changes gut microbial composition. We determined whether the gut microbiota in humans after restrictive or malabsorptive bariatric surgery was sufficient to lower blood glucose.

Design Women with obesity and T2D had biliopancreatic diversion with duodenal switch (BPD-DS) or laparoscopic sleeve gastrectomy (LSG). Faecal samples from the same patient before and after each surgery were used to colonise rodents, and determinants of blood glucose control were assessed.

Results Glucose tolerance was improved in germ-free mice orally colonised for 7 weeks with human microbiota after either BPD-DS or LSG, whereas food intake, fat mass, insulin resistance, secretion and clearance were unchanged. Mice colonised with microbiota post-BPD-DS had lower villus height/width and crypt depth in the distal jejunum and lower intestinal glucose absorption. Inhibition of sodium-glucose cotransporter (Sglt)1 abrogated microbiota-transmissible improvements in blood glucose control in mice. In specific pathogen-free (SPF) rats, intrajejunal colonisation for 4 weeks with microbiota post-BPD-DS was sufficient to improve blood glucose control, which was negated after intrajejunal Sglt-1 inhibition. Higher Parabacteroides and lower Blautia coincided with improvements in blood glucose control after colonisation with human bacteria post-BPD-DS and LSG.

Conclusion Exposure of rodents to human gut microbiota after restrictive or malabsorptive bariatric surgery improves glycaemic control. The gut microbiota after bariatric surgery is a standalone factor that alters upper gut intestinal morphology and lowers Sglt1-mediated intestinal glucose absorption, which improves blood glucose control independently from changes in obesity, insulin or insulin resistance.

  • glucose metabolism
  • obesity surgery
  • intestinal microbiology
  • diabetes mellitus
  • intestinal absorption

Data availability statement

Data are available on reasonable request.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Footnotes

  • Twitter @fernando_anhe, @BeatriceSY_Choi, @TKTLam, @SchertzerLab

  • Contributors FFA, JS, AM, TKTL and AT derived the hypothesis and researched the data. FFA conducted experiments, analysed the data and wrote the manuscript. SZ and S-YZ conducted experiments and analysed the data. BS-YC and NGB conducted experiments. CYC and KPF helped with experiments. LB performed surgeries. JS, AM and TKTL edited the manuscript. All authors contributed with data discussion and approved the manuscript prior to its submission. JS is the guarantor.

  • Funding This study was supported by a team grant from the Canadian Institutes of Health Research (CIHR) on bariatric care (TB2-138776), an Investigator-initiated study grant from Johnson & Johnson Medical Companies (Grant ETH-14-610) and a CIHR Canadian Microbiome Initiative 2 (CMI2) team grant (MRT-168045).

  • Disclaimer Funding sources for the trial had no role in the design, conduct or management of the study, in data collection, analysis or interpretation of data, or in the preparation of the present manuscript and decision to publish.

  • Competing interests FFA and S-YZ have Canadian Institutes of Health Research (CIHR) postdoctoral fellowships. AT and LB are recipients of research grant support from Johnson & Johnson Medical Companies, Bodynov and Medtronic for studies on bariatric surgery and the Research Chair in Bariatric and Metabolic Surgery at IUCPQ and Laval University. TKTL holds a Canada Research Chair in Diabetes and Obesity and a JK. McIvor endowed chair in Diabetes Research. JS holds a Canada Research Chair in Metabolic Inflammation. AM was supported by a CIHR/Pfizer research Chair in the pathogenesis of insulin resistance and cardiovascular diseases. JS is the guarantor of the study and, as such, assumes full responsability for the work and conduct of the study.

  • Patient and public involvement Patients and/or the public were involved in the design, or conduct, or reporting, or dissemination plans of this research. Refer to the 'Methods' section for further details.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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