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

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 - Salojärvi, 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 - Olde Damink, Steven W.M.

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

Y1 - 2017/10

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 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. Kootte et al. show that fecal microbiota transplantation from lean donors to obese patients with metabolic syndrome improves insulin sensitivity, a transient effect associated with changes in microbiota composition and fasting plasma metabolites. Baseline fecal microbiota composition in recipients predicts the response to lean donor fecal microbiota transplantation.

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 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. Kootte et al. show that fecal microbiota transplantation from lean donors to obese patients with metabolic syndrome improves insulin sensitivity, a transient effect associated with changes in microbiota composition and fasting plasma metabolites. Baseline fecal microbiota composition in recipients predicts the response to lean donor fecal microbiota transplantation.

KW - fecal microbiota transplantation

KW - insulin sensitivity

KW - intestinal microbiota composition

KW - plasma metabolites

U2 - 10.1016/j.cmet.2017.09.008

DO - 10.1016/j.cmet.2017.09.008

M3 - Journal article

C2 - 28978426

AN - SCOPUS:85032366326

SN - 1550-4131

VL - 26

SP - 611-619.e6

JO - Cell Metabolism

JF - Cell Metabolism

IS - 4

ER -