Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition

Ruud S Kootte; Evgeni Levin; Jarkko Salojärvi; Loek P Smits; Annick V Hartstra; Shanti D Udayappan; Gerben Hermes; Kristien E Bouter; Annefleur M Koopen; Jens J Holst; Filip K Knop; Ellen E Blaak; Jing Zhao; Hauke Smidt; Amy C Harms; Thomas Hankemeijer; Jacques J G H M Bergman; Hans A Romijn; Frank G Schaap; Steven W M Olde Damink; Mariette T Ackermans; Geesje M Dallinga-Thie; Erwin Zoetendal; Willem M de Vos; Mireille J Serlie; Erik S G Stroes; Albert K Groen; Max Nieuwdorp

doi:10.1016/j.cmet.2017.09.008

Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition

Cell Metab. 2017 Oct 3;26(4):611-619.e6. doi: 10.1016/j.cmet.2017.09.008.

Authors

Ruud S Kootte¹, Evgeni Levin², Jarkko Salojärvi³, Loek P Smits⁴, Annick V Hartstra⁴, Shanti D Udayappan⁴, Gerben Hermes⁵, Kristien E Bouter⁴, Annefleur M Koopen⁴, Jens J Holst⁶, Filip K Knop⁷, Ellen E Blaak⁸, Jing Zhao⁴, Hauke Smidt⁵, Amy C Harms⁹, Thomas Hankemeijer⁹, Jacques J G H M Bergman¹⁰, Hans A Romijn¹¹, Frank G Schaap¹², Steven W M Olde Damink¹², Mariette T Ackermans¹³, Geesje M Dallinga-Thie⁴, Erwin Zoetendal⁵, Willem M de Vos¹⁴, Mireille J Serlie¹⁵, Erik S G Stroes⁴, Albert K Groen¹, Max Nieuwdorp¹⁶

Affiliations

¹ Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands; Top Institute of Food and Nutrition, 6700 AN Wageningen, the Netherlands.
² Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands; Horaizon BV, 3062 ME Rotterdam, the Netherlands.
³ Department of Biosciences, University of Helsinki, 00014 Helsinki, Finland.
⁴ Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
⁵ Top Institute of Food and Nutrition, 6700 AN Wageningen, the Netherlands; Laboratory of Microbiology, Wageningen University, 6703 HB Wageningen, the Netherlands.
⁶ NNF Center for Basic Metabolic Research, Department of Biomedical Sciences, the Panum Institute, University of Copenhagen, 2200 Copenhagen, Denmark.
⁷ Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, 2900 Hellerup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
⁸ Top Institute of Food and Nutrition, 6700 AN Wageningen, the Netherlands; Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 6229 ER Maastricht, the Netherlands.
⁹ Leiden Academic Centre for Drug Research, Leiden University, Leiden, the Netherlands.
¹⁰ Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
¹¹ Department of Internal Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
¹² Department of Surgery, Maastricht University Medical Center, 6229 ER Maastricht, the Netherlands.
¹³ Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, 1105 AZ Amsterdam, the Netherlands.
¹⁴ Laboratory of Microbiology, Wageningen University, 6703 HB Wageningen, the Netherlands; Immunobiology Research Program, Department of Bacteriology and Immunology, University of Helsinki, 00014 Helsinki, Finland.
¹⁵ Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands.
¹⁶ Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands; Top Institute of Food and Nutrition, 6700 AN Wageningen, the Netherlands; Department of Internal Medicine, VUMC, Free University, Amsterdam, the Netherlands; Wallenberg Laboratory, Sahlgrenska Hospital, University of Gothenburg, Gothenburg, Sweden. Electronic address: m.nieuwdorp@amc.uva.nl.

PMID: 28978426
DOI: 10.1016/j.cmet.2017.09.008

Abstract

The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own (autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition. We also observed changes in plasma metabolites such as γ-aminobutyric acid and show that metabolic response upon allogenic FMT (defined as improved insulin sensitivity 6 weeks after FMT) is dependent on decreased fecal microbial diversity at baseline. In conclusion, the beneficial effects of lean donor FMT on glucose metabolism are associated with changes in intestinal microbiota and plasma metabolites and can be predicted based on baseline fecal microbiota composition.

Keywords: fecal microbiota transplantation; insulin sensitivity; intestinal microbiota composition; plasma metabolites.

MeSH terms

Blood Glucose / analysis
Blood Glucose / metabolism
Fecal Microbiota Transplantation* / methods
Feces / microbiology
Gastrointestinal Microbiome*
Humans
Insulin Resistance*
Male
Metabolic Syndrome / blood
Metabolic Syndrome / metabolism
Metabolic Syndrome / microbiology
Metabolic Syndrome / therapy*
Middle Aged
Transplantation, Autologous / methods
Transplantation, Homologous / methods
gamma-Aminobutyric Acid / blood
gamma-Aminobutyric Acid / metabolism

Substances

Blood Glucose
gamma-Aminobutyric Acid