Molecular Metabolism (Dec 2020)
Infusion of donor feces affects the gut–brain axis in humans with metabolic syndrome
- Annick V. Hartstra,
- Valentina Schüppel,
- Sultan Imangaliyev,
- Anouk Schrantee,
- Andrei Prodan,
- Didier Collard,
- Evgeni Levin,
- Geesje Dallinga-Thie,
- Mariette T. Ackermans,
- Maaike Winkelmeijer,
- Stefan R. Havik,
- Amira Metwaly,
- Ilias Lagkouvardos,
- Anika Nier,
- Ina Bergheim,
- Mathias Heikenwalder,
- Andreas Dunkel,
- Aart J. Nederveen,
- Gerhard Liebisch,
- Giulia Mancano,
- Sandrine P. Claus,
- Alfonso Benítez-Páez,
- Susanne E. la Fleur,
- Jacques J. Bergman,
- Victor Gerdes,
- Yolanda Sanz,
- Jan Booij,
- Elles Kemper,
- Albert K. Groen,
- Mireille J. Serlie,
- Dirk Haller,
- Max Nieuwdorp
Affiliations
- Annick V. Hartstra
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Valentina Schüppel
- Chair of Nutrition and Immunology, Technical University of Munich, Freising, Germany
- Sultan Imangaliyev
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Anouk Schrantee
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Andrei Prodan
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Didier Collard
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Evgeni Levin
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Geesje Dallinga-Thie
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Mariette T. Ackermans
- Laboratory of Endocrinology, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Maaike Winkelmeijer
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Stefan R. Havik
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Amira Metwaly
- Chair of Nutrition and Immunology, Technical University of Munich, Freising, Germany
- Ilias Lagkouvardos
- ZIEL-Institute for Food and Health, Technical University of Munich, Freising, Germany
- Anika Nier
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Austria
- Ina Bergheim
- Department of Nutritional Sciences, Molecular Nutritional Science, University of Vienna, Austria
- Mathias Heikenwalder
- German Cancer Research Center (DKFZ), Division of Chronic Inflammation and Cancer, Heidelberg, Germany
- Andreas Dunkel
- Leibniz-Institute for Food Systems Biology, Technical University of Munich, Freising, Germany
- Aart J. Nederveen
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Gerhard Liebisch
- Department of Laboratory Medicine, University of Regensburg, Regensburg, Germany
- Giulia Mancano
- Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom
- Sandrine P. Claus
- Department of Food and Nutritional Sciences, University of Reading, Reading, United Kingdom
- Alfonso Benítez-Páez
- Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain
- Susanne E. la Fleur
- Laboratory of Endocrinology, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Jacques J. Bergman
- Department of Gastroenterology, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Victor Gerdes
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Yolanda Sanz
- Institute of Agrochemistry and Food Technology, Spanish National Research Council (IATA-CSIC), Valencia, Spain
- Jan Booij
- Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Elles Kemper
- Department of Clinical Pharmacy, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Albert K. Groen
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Mireille J. Serlie
- Department of Endocrinology and Metabolism, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands
- Dirk Haller
- Chair of Nutrition and Immunology, Technical University of Munich, Freising, Germany; ZIEL-Institute for Food and Health, Technical University of Munich, Freising, Germany
- Max Nieuwdorp
- Department of Internal and Vascular Medicine, Amsterdam University Medical Centers, location AMC, Amsterdam, the Netherlands; Corresponding author. Department of Internal and Vascular Medicine, Chair Diabetes, Amsterdam University Medical Centers, Location AMC and VUMC, Meibergdreef 9, Room D3-211, 1105AZ, Amsterdam, the Netherlands. Fax: +31205669158.
- Journal volume & issue
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Vol. 42
p. 101076
Abstract
Objective: Increasing evidence indicates that intestinal microbiota play a role in diverse metabolic processes via intestinal butyrate production. Human bariatric surgery data suggest that the gut-brain axis is also involved in this process, but the underlying mechanisms remain unknown. Methods: We compared the effect of fecal microbiota transfer (FMT) from post-Roux-en-Y gastric bypass (RYGB) donors vs oral butyrate supplementation on (123I-FP-CIT-determined) brain dopamine transporter (DAT) and serotonin transporter (SERT) binding as well as stable isotope-determined insulin sensitivity at baseline and after 4 weeks in 24 male and female treatment-naïve metabolic syndrome subjects. Plasma metabolites and fecal microbiota were also determined at these time points. Results: We observed an increase in brain DAT after donor FMT compared to oral butyrate that reduced this binding. However, no effect on body weight and insulin sensitivity was demonstrated after post-RYGB donor feces transfer in humans with metabolic syndrome. Increases in fecal levels of Bacteroides uniformis were significantly associated with an increase in DAT, whereas increases in Prevotella spp. showed an inverse association. Changes in the plasma metabolites glycine, betaine, methionine, and lysine (associated with the S-adenosylmethionine cycle) were also associated with altered striatal DAT expression. Conclusions: Although more and larger studies are needed, our data suggest a potential gut microbiota-driven modulation of brain dopamine and serotonin transporters in human subjects with obese metabolic syndrome. These data also suggest the presence of a gut-brain axis in humans that can be modulated. NTR registration: 4488.
