Infusion of donor feces affects the gut–brain axis in humans with metabolic syndrome

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.

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Main Authors: Hartstra, Annick V., Schüppel, Valentina, Imangaliyev, Sultan, Schrantee, Anouk, Prodan, Andrei, Collard, Didier, Levin, Evgeni, Dallinga-Thie, Geesje, Ackermans, Mariette T., Winkelmeijer, Maaike, Havik, Stefan R., Metwaly, Amira, Lagkouvardos, Ilias, Nier, Anika, Bergheim, Ina, Heikenwalder, Mathias, Dunkel, Andreas, Nederveen, Aart J., Liebisch, Gerhard, Mancano, Giulia, Claus, Sandrine P., Benítez-Páez, Alfonso, la Fleur, Susanne E., Bergman, Jacques J., Gerdes, Victor, Sanz Herranz, Yolanda, Booij, Jan, Kemper, Elles, Groen, Albert K., Serlie, Mireille J., Haller, Dirk, Nieuwdorp, Max
Other Authors: European Commission
Format: artículo biblioteca
Language:English
Published: Elsevier 2020-09-08
Subjects:Obesity, Gut microbiota, Gut-brain axis, Metabolites,
Online Access:http://hdl.handle.net/10261/246782
http://dx.doi.org/10.13039/501100000780
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spelling dig-iata-es-10261-2467822021-12-27T16:03:09Z Infusion of donor feces affects the gut–brain axis in humans with metabolic syndrome Hartstra, Annick V. Schüppel, Valentina Imangaliyev, Sultan Schrantee, Anouk Prodan, Andrei Collard, Didier Levin, Evgeni Dallinga-Thie, Geesje Ackermans, Mariette T. Winkelmeijer, Maaike Havik, Stefan R. Metwaly, Amira Lagkouvardos, Ilias Nier, Anika Bergheim, Ina Heikenwalder, Mathias Dunkel, Andreas Nederveen, Aart J. Liebisch, Gerhard Mancano, Giulia Claus, Sandrine P. Benítez-Páez, Alfonso la Fleur, Susanne E. Bergman, Jacques J. Gerdes, Victor Sanz Herranz, Yolanda Booij, Jan Kemper, Elles Groen, Albert K. Serlie, Mireille J. Haller, Dirk Nieuwdorp, Max European Commission Obesity Gut microbiota Gut-brain axis Metabolites 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. This study was funded by FP7-EU consortium MyNewGut grant agreement no. 613979 (to which A.V.H. was appointed). M. Nieuwdorp is supported by a ZONMW-VIDI grant 2013 (016.146.327). Peer reviewed 2021-07-29T05:59:45Z 2021-07-29T05:59:45Z 2020-09-08 artículo http://purl.org/coar/resource_type/c_6501 Molecular Metabolism 42: 101076 (2020) 2212-8778 http://hdl.handle.net/10261/246782 10.1016/j.molmet.2020.101076 http://dx.doi.org/10.13039/501100000780 32916306 en #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/EC/FP7/613979 Publisher's version https://doi.org/10.1016/j.molmet.2020.101076 Sí open Elsevier
institution IATA ES
collection DSpace
country España
countrycode ES
component Bibliográfico
access En linea
databasecode dig-iata-es
tag biblioteca
region Europa del Sur
libraryname Biblioteca del IATA España
language English
topic Obesity
Gut microbiota
Gut-brain axis
Metabolites
Obesity
Gut microbiota
Gut-brain axis
Metabolites
spellingShingle Obesity
Gut microbiota
Gut-brain axis
Metabolites
Obesity
Gut microbiota
Gut-brain axis
Metabolites
Hartstra, Annick V.
Schüppel, Valentina
Imangaliyev, Sultan
Schrantee, Anouk
Prodan, Andrei
Collard, Didier
Levin, Evgeni
Dallinga-Thie, Geesje
Ackermans, Mariette T.
Winkelmeijer, Maaike
Havik, Stefan R.
Metwaly, Amira
Lagkouvardos, Ilias
Nier, Anika
Bergheim, Ina
Heikenwalder, Mathias
Dunkel, Andreas
Nederveen, Aart J.
Liebisch, Gerhard
Mancano, Giulia
Claus, Sandrine P.
Benítez-Páez, Alfonso
la Fleur, Susanne E.
Bergman, Jacques J.
Gerdes, Victor
Sanz Herranz, Yolanda
Booij, Jan
Kemper, Elles
Groen, Albert K.
Serlie, Mireille J.
Haller, Dirk
Nieuwdorp, Max
Infusion of donor feces affects the gut–brain axis in humans with metabolic syndrome
description 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.
author2 European Commission
author_facet European Commission
Hartstra, Annick V.
Schüppel, Valentina
Imangaliyev, Sultan
Schrantee, Anouk
Prodan, Andrei
Collard, Didier
Levin, Evgeni
Dallinga-Thie, Geesje
Ackermans, Mariette T.
Winkelmeijer, Maaike
Havik, Stefan R.
Metwaly, Amira
Lagkouvardos, Ilias
Nier, Anika
Bergheim, Ina
Heikenwalder, Mathias
Dunkel, Andreas
Nederveen, Aart J.
Liebisch, Gerhard
Mancano, Giulia
Claus, Sandrine P.
Benítez-Páez, Alfonso
la Fleur, Susanne E.
Bergman, Jacques J.
Gerdes, Victor
Sanz Herranz, Yolanda
Booij, Jan
Kemper, Elles
Groen, Albert K.
Serlie, Mireille J.
Haller, Dirk
Nieuwdorp, Max
format artículo
topic_facet Obesity
Gut microbiota
Gut-brain axis
Metabolites
author Hartstra, Annick V.
Schüppel, Valentina
Imangaliyev, Sultan
Schrantee, Anouk
Prodan, Andrei
Collard, Didier
Levin, Evgeni
Dallinga-Thie, Geesje
Ackermans, Mariette T.
Winkelmeijer, Maaike
Havik, Stefan R.
Metwaly, Amira
Lagkouvardos, Ilias
Nier, Anika
Bergheim, Ina
Heikenwalder, Mathias
Dunkel, Andreas
Nederveen, Aart J.
Liebisch, Gerhard
Mancano, Giulia
Claus, Sandrine P.
Benítez-Páez, Alfonso
la Fleur, Susanne E.
Bergman, Jacques J.
Gerdes, Victor
Sanz Herranz, Yolanda
Booij, Jan
Kemper, Elles
Groen, Albert K.
Serlie, Mireille J.
Haller, Dirk
Nieuwdorp, Max
author_sort Hartstra, Annick V.
title Infusion of donor feces affects the gut–brain axis in humans with metabolic syndrome
title_short Infusion of donor feces affects the gut–brain axis in humans with metabolic syndrome
title_full Infusion of donor feces affects the gut–brain axis in humans with metabolic syndrome
title_fullStr Infusion of donor feces affects the gut–brain axis in humans with metabolic syndrome
title_full_unstemmed Infusion of donor feces affects the gut–brain axis in humans with metabolic syndrome
title_sort infusion of donor feces affects the gut–brain axis in humans with metabolic syndrome
publisher Elsevier
publishDate 2020-09-08
url http://hdl.handle.net/10261/246782
http://dx.doi.org/10.13039/501100000780
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