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

• Published in: Cell metabolism Vol. 26; no. 4; pp. 611 - 619.e6
• Main Authors: Kootte, Ruud S., Levin, Evgeni, Salojärvi, Jarkko, Smits, Loek P., Hartstra, Annick V., Udayappan, Shanti D., Hermes, Gerben, Bouter, Kristien E., Koopen, Annefleur M., Holst, Jens J., Knop, Filip K., Blaak, Ellen E., Zhao, Jing, Smidt, Hauke, Harms, Amy C., Hankemeijer, Thomas, Bergman, Jacques J.G.H.M., Romijn, Hans A., Schaap, Frank G., Olde Damink, Steven W.M., Ackermans, Mariette T., Dallinga-Thie, Geesje M., Zoetendal, Erwin, de Vos, Willem M., Serlie, Mireille J., Stroes, Erik S.G., Groen, Albert K., Nieuwdorp, Max
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03-10-2017
• Subjects: bacteria; bile-acid metabolism; Blood Glucose - analysis; Blood Glucose - metabolism; Cell Biology; Cellbiologi; chain; Endocrinology & Metabolism; Endocrinology and Diabetes; Endokrinologi och diabetes; fatty-acids; fecal microbiota transplantation; Fecal Microbiota Transplantation - methods; Feces - microbiology; gamma-Aminobutyric Acid - blood; gamma-Aminobutyric Acid - metabolism; Gastrointestinal Microbiome; gut microbiota; Humans; Insulin Resistance; insulin sensitivity; intestinal microbiota composition; lactobacillus; Male; markers; Metabolic Syndrome - blood; Metabolic Syndrome - metabolism; Metabolic Syndrome - microbiology; Metabolic Syndrome - therapy; Microbiology in the medical area; Middle Aged; Mikrobiologi inom det medicinska området; obesity; plasma metabolites; recurrent clostridium-difficile; selection; transplantation; Transplantation, Autologous - methods; Transplantation, Homologous - methods; insulin sensitivity; plasma metabolites; intestinal microbiota composition; fecal microbiota transplantation
• ISSN: 1550-4131; 1932-7420
• DOI: 10.1016/j.cmet.2017.09.008

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.
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•Lean donor FMT in obese metabolic syndrome patients improves insulin sensitivity•Beneficial effects of lean donor FMT are transient•Improvement in insulin sensitivity is linked to changes in plasma metabolites•Response to lean donor FMT is driven by 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.