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Original article
Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time
  1. Pieter de Groot1,
  2. Torsten Scheithauer1,
  3. Guido J Bakker1,
  4. Andrei Prodan1,
  5. Evgeni Levin1,
  6. Muhammad Tanweer Khan2,
  7. Hilde Herrema1,
  8. Mariette Ackermans1,
  9. Mireille J M Serlie1,
  10. Maurits de Brauw3,
  11. Johannes H M Levels1,
  12. Amber Sales1,
  13. Victor E Gerdes1,
  14. Marcus Ståhlman2,
  15. Alinda W M Schimmel1,
  16. Geesje Dallinga-Thie1,
  17. Jacques JGHM Bergman4,
  18. Frits Holleman1,
  19. Joost B L Hoekstra1,
  20. Albert Groen1,
  21. Fredrik Bäckhed2,
  22. Max Nieuwdorp1
  1. 1Department of Internal and Vascular Medicine, Amsterdam University Medical Centres, Amsterdam, The Netherlands
  2. 2Wallenberg Laboratory, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, Goteborgs Universitet, Gothenburg, Sweden
  3. 3Department of Surgery, Spaarne Gasthuis, Haarlem, The Netherlands
  4. 4Department of Gastroenterology, Amsterdam University Medical Centres, Amsterdam, The Netherlands
  1. Correspondence to Dr Max Nieuwdorp, Department of Internal and Vascular Medicine, Amsterdam University Medical Centres, Amsterdam 1105 AZ, The Netherlands; m.nieuwdorp{at}amc.nl

Abstract

Objective Bariatric surgery improves glucose metabolism. Recent data suggest that faecal microbiota transplantation (FMT) using faeces from postbariatric surgery diet-induced obese mice in germ-free mice improves glucose metabolism and intestinal homeostasis. We here investigated whether allogenic FMT using faeces from post-Roux-en-Y gastric bypass donors (RYGB-D) compared with using faeces from metabolic syndrome donors (METS-D) has short-term effects on glucose metabolism, intestinal transit time and adipose tissue inflammation in treatment-naïve, obese, insulin-resistant male subjects.

Design Subjects with metabolic syndrome (n=22) received allogenic FMT either from RYGB-D or METS-D. Hepatic and peripheral insulin sensitivity as well as lipolysis were measured at baseline and 2 weeks after FMT by hyperinsulinaemic euglycaemic stable isotope (2H2-glucose and 2H5-glycerol) clamp. Secondary outcome parameters were changes in resting energy expenditure, intestinal transit time, faecal short-chain fatty acids (SCFA) and bile acids, and inflammatory markers in subcutaneous adipose tissue related to intestinal microbiota composition. Faecal SCFA, bile acids, glycaemic control and inflammatory parameters were also evaluated at 8 weeks.

Results We observed a significant decrease in insulin sensitivity 2 weeks after allogenic METS-D FMT (median rate of glucose disappearance: from 40.6 to 34.0 µmol/kg/min; p<0.01). Moreover, a trend (p=0.052) towards faster intestinal transit time following RYGB-D FMT was seen. Finally, we observed changes in faecal bile acids (increased lithocholic, deoxycholic and (iso)lithocholic acid after METS-D FMT), inflammatory markers (decreased adipose tissue chemokine ligand 2 (CCL2) gene expression and plasma CCL2 after RYGB-D FMT) and changes in several intestinal microbiota taxa.

Conclusion Allogenic FMT using METS-D decreases insulin sensitivity in metabolic syndrome recipients when compared with using post-RYGB-D. Further research is needed to delineate the role of donor characteristics in FMT efficacy in human insulin-resistant subjects.

Trial registration number NTR4327.

  • diabetes mellitus
  • intestinal microbiology
  • gastrointestinal transit
  • bile acid metabolism

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Footnotes

  • Contributors PdG, GJB, AS performed the patient visits. TS, MTK, HH, MA, MS, JHML, AWMS, GD-T, MJS performed the wet lab analyses. PdG, AP, EL performed the data analyses. MdB was involved in the recruitment of bariatric surgery subjects. JJGHMB was involved in performing the gastroduodenoscopies. PdG, MN drafted the manuscript. FH, JBLH, AG, FB, MN supervised the project. All authors critically appraised the manuscript and the revised manuscript.

  • Funding MN is supported by a ZONMW-VIDI grant 2013 (016.146.327), a Dutch Heart Foundation CVON IN CONTROL Young Talent Grant 2013 and a JPl HDHL MICRODIET project (50-52905-98-620). FB is Torsten Söderberg professor in medicine and recipient of a European Research Council Consolidator Grant (615362 - METABASE). The study reported here was additionally supported by Leducq consortium grant 17CVD01 and Novo Nordisk Foundation GUT-MMM grant 2016.

  • Competing interests MN is in the Scientific Advisory Board of Caelus Pharmaceuticals, the Netherlands. FB is in the Scientific Advisory Board of MetaboGen, Sweden.

  • Ethics approval The study was approved by the local institutional review board of the Academic Medical Centre (AMC) in Amsterdam, The Netherlands and conducted at the AMC in accordance with the Declaration of Helsinki.

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

  • Patient consent for publication Not required.

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