Presentation Abstract

Presentation Number: 90
Title: Metabolic effects of transplanting gut microbiota from lean donors to subjects with metabolic syndrome
Presentation Time: Wednesday, Sep 22, 2010, 12:00 PM -12:15 PM
Authors: A. Vrieze1, F. Holleman1, M.J. Serlie2, M.T. Ackermans2, G.M. Dallinga-Thie1, A.K. Groen3, E. van Nood1, J.F.W. Bartelsman4, R. Oozeer5, E. Zoetendal6, W.M. de Vos6,7, J.B.L. Hoekstra1, M. Nieuwdorp1;
1Department of Internal and Vascular Medicine, Academic Medical Centre, Amsterdam, Netherlands, 2Department of Endocrinology and Metabolism, Academic Medical Centre, Amsterdam, Netherlands, 3Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Netherlands, 4Department of Gastroenterology, Academic Medical Centre, Amsterdam, Netherlands, 5Danone Research Center, Paris, France, 6Laboratory of Microbiology, Wageningen University, Wageningen, Netherlands, 7Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
Keyword: 19 Insulin sensitivity and resistance
Abstract: Background: Recent data in animal models revealed that obesity is associated with substantial changes in composition and metabolic function of gut microbiota. Moreover, colonization of germ-free mice with faeces harvested from obese mice resulted in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. However, data on the role of gutmicrobiota in human obesity are scarce. Thus, our aim was to examine the effect of faecal infusions derived from lean healthy donors on gut microbiota composition, glucose and lipids in metabolic syndrome.
Methods: This study was a double-blind, randomised controlled trial. A total of 18 male subjects with newly diagnosed metabolic syndrome (BMI≥30 kg/m2, FPG>5.6mmol/L, TG>1,6 mmol/L with no medication use) underwent jejunum biopsies and subsequent polyethylene-glycol bowel lavage through duodenal tube followed by random assignment to either allogenic (from lean male donors with BMI<23 kg/m2, n=9) or autologous faecal transplantation (reinfusion of own collected faeces, n=9). We studied changes in sigmoidal microbiota composition and fasting lipidprofiles at 0.5, 2, 6 and 12 weeks after faecal transplantation. Weight, jejunal gut microbiota (epithelial biopsy) and glucose metabolism (peripheral and hepatic insulin sensitivity as assessed by hyperinsulinemic euglycemic clamp with stable isotopes) were studied before and 6 weeks after transplantation.
Results: Lean subjects were characterized by different sigmoidal gutmicrobiota compared to obese subjects (by HITChip phylogenetic microarray analysis). Fasting levels of TG-rich lipoproteins (TG/ApoB ratio) were significantly reduced following donor faeces (1.43 ± 0.21 to 1.11 ± 0.18, p<0.01) with no effect after autologous faeces infusion. REE and basal endogenous glucose production (EGP) did not change in both groups after faecal infusion. Although weight remained stable, an improvement in both peripheral (Rd) and hepatic insulin sensitivity (suppression of EGP) was found 6 weeks after allogenic faeces (median Rd: from 26.2 to 45.3 μmol/kg.min, p=0.02 and EGP suppression: from 51.5 to 61.6 %, p=0.08) while no significant changes were observed in the autologous treatment group (Rd: from 21.0 to 19.5 μmol/kg.min and EGP suppression:from 53.8 to 52.4 %, ns). Changes in jejunal microbiota are currently analyzed.
Conclusion: Lean donor faecal infusion improves hepatic and peripheral insulin resistance as well as fasting lipid levels in obese individuals with the metabolic syndrome underscoring the potential role of gut microbiota in the disturbances of glucose and lipid metabolism in obesity. Our data could provide pathophysiological insight in the metabolic deviations in obese subjects and a rationale for therapeutic intervention.
Supported By: VENI grant (NWO ZonMW) to M. Nieuwdorp