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

Ruud S. Kootte; Evgeni Levin; Jarkko Salojarvi; 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

Ruud S. Kootte, Evgeni Levin, Jarkko Salojarvi, 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 DaminkMariette T. Ackermans, Geesje M. Dallinga-Thie, Erwin Zoetendal, Willem M. de Vos, Mireille J. Serlie, Erik S. G. Stroes, Albert K. Groen, Max Nieuwdorp^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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 gamma-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.

Original language	English
Pages (from-to)	611-619.e6
Number of pages	15
Journal	Cell Metabolism
Volume	26
Issue number	4
DOIs	https://doi.org/10.1016/j.cmet.2017.09.008
Publication status	Published - 3 Oct 2017

Keywords

RECURRENT CLOSTRIDIUM-DIFFICILE
BILE-ACID METABOLISM
CHAIN FATTY-ACIDS
GUT MICROBIOTA
MARKERS
OBESITY
TRANSPLANTATION
LACTOBACILLUS
SELECTION
BACTERIA

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Cite this

Kootte, R. S., Levin, E., Salojarvi, J., Smits, L. P., Hartstra, A. V., Udayappan, S. D., Hermes, G., Bouter, K. E., Koopen, A. M., Holst, J. J., Knop, F. K., Blaak, E. E., Zhao, J., Smidt, H., Harms, A. C., Hankemeijer, T., Bergman, J. J. G. H. M., Romijn, H. A., Schaap, F. G., ... Nieuwdorp, M. (2017). Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition. Cell Metabolism, 26(4), 611-619.e6. https://doi.org/10.1016/j.cmet.2017.09.008

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

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 gamma-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 = "RECURRENT CLOSTRIDIUM-DIFFICILE, BILE-ACID METABOLISM, CHAIN FATTY-ACIDS, GUT MICROBIOTA, MARKERS, OBESITY, TRANSPLANTATION, LACTOBACILLUS, SELECTION, BACTERIA",

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

year = "2017",

month = oct,

day = "3",

doi = "10.1016/j.cmet.2017.09.008",

language = "English",

volume = "26",

pages = "611--619.e6",

journal = "Cell Metabolism",

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Kootte, RS, Levin, E, Salojarvi, J, Smits, LP, Hartstra, AV, Udayappan, SD, Hermes, G, Bouter, KE, Koopen, AM, Holst, JJ, Knop, FK, Blaak, EE, Zhao, J, Smidt, H, Harms, AC, Hankemeijer, T, Bergman, JJGHM, Romijn, HA, Schaap, FG , Damink, SWMO, Ackermans, MT, Dallinga-Thie, GM, Zoetendal, E, de Vos, WM, Serlie, MJ, Stroes, ESG, Groen, AK & Nieuwdorp, M 2017, 'Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition', Cell Metabolism, vol. 26, no. 4, pp. 611-619.e6. https://doi.org/10.1016/j.cmet.2017.09.008

TY - JOUR

T1 - Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition

AU - Kootte, Ruud S.

AU - Levin, Evgeni

AU - Salojarvi, Jarkko

AU - Smits, Loek P.

AU - Hartstra, Annick V.

AU - Udayappan, Shanti D.

AU - Hermes, Gerben

AU - Bouter, Kristien E.

AU - Koopen, Annefleur M.

AU - Holst, Jens J.

AU - Knop, Filip K.

AU - Blaak, Ellen E.

AU - Zhao, Jing

AU - Smidt, Hauke

AU - Harms, Amy C.

AU - Hankemeijer, Thomas

AU - Bergman, Jacques J. G. H. M.

AU - Romijn, Hans A.

AU - Schaap, Frank G.

AU - Damink, Steven W. M. Olde

AU - Ackermans, Mariette T.

AU - Dallinga-Thie, Geesje M.

AU - Zoetendal, Erwin

AU - de Vos, Willem M.

AU - Serlie, Mireille J.

AU - Stroes, Erik S. G.

AU - Groen, Albert K.

AU - Nieuwdorp, Max

PY - 2017/10/3

Y1 - 2017/10/3

N2 - 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 gamma-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.

AB - 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 gamma-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.

KW - RECURRENT CLOSTRIDIUM-DIFFICILE

KW - BILE-ACID METABOLISM

KW - CHAIN FATTY-ACIDS

KW - GUT MICROBIOTA

KW - MARKERS

KW - OBESITY

KW - TRANSPLANTATION

KW - LACTOBACILLUS

KW - SELECTION

KW - BACTERIA

U2 - 10.1016/j.cmet.2017.09.008

DO - 10.1016/j.cmet.2017.09.008

M3 - Article

C2 - 28978426

SN - 1550-4131

VL - 26

SP - 611-619.e6

JO - Cell Metabolism

JF - Cell Metabolism

IS - 4

ER -