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Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time

Journal article
Authors P. De Groot
T. Scheithauer
G. J. Bakker
A. Prodan
E. Levin
Muhammad Tanweer Khan
H. Herrema
M. Ackermans
M. J. M. Serlie
M. De Brauw
J. H. M. Levels
A. Sales
Marcus Ståhlman
A. W. M. Schimmel
G. Dallinga-Thie
J. J. Bergman
F. Holleman
J. B. L. Hoekstra
A. Groen
Fredrik Bäckhed
M. Nieuwdorp
Published in Gut
ISSN 0017-5749
Publication year 2019
Published at Wallenberg Laboratory
Institute of Medicine, Department of Molecular and Clinical Medicine
Language en
Links dx.doi.org/10.1136/gutjnl-2019-3183...
Keywords bile acid metabolism, diabetes mellitus, gastrointestinal transit, intestinal microbiology
Subject categories Endocrinology and Diabetes

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. © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

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