Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects: a randomised double-blind placebo-controlled cross-over study

Research output: Contribution to journalJournal articlepeer-review

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Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects : a randomised double-blind placebo-controlled cross-over study. / Koopen, Annefleur; Witjes, Julia; Wortelboer, Koen; Majait, Soumia; Prodan, Andrei; Levin, Evgeni; Herrema, Hilde; Winkelmeijer, Maaike; Aalvink, Steven; Bergman, Jacques J. G. H. M.; Havik, Stephan; Hartmann, Bolette; Levels, Han; Bergh, Per-Olof; van Son, Jamie; Balvers, Manon; Bastos, Diogo Mendes; Stroes, Erik; Groen, Albert K.; Henricsson, Marcus; Kemper, Ellis Marleen; Holst, Jens; Strauch, Christopher M.; Hazen, Stanley L.; Backhed, Fredrik; De Vos, Willem M.; Nieuwdorp, Max; Rampanelli, Elena.

In: Gut, Vol. 71, 2022, p. 1577-1587.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Koopen, A, Witjes, J, Wortelboer, K, Majait, S, Prodan, A, Levin, E, Herrema, H, Winkelmeijer, M, Aalvink, S, Bergman, JJGHM, Havik, S, Hartmann, B, Levels, H, Bergh, P-O, van Son, J, Balvers, M, Bastos, DM, Stroes, E, Groen, AK, Henricsson, M, Kemper, EM, Holst, J, Strauch, CM, Hazen, SL, Backhed, F, De Vos, WM, Nieuwdorp, M & Rampanelli, E 2022, 'Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects: a randomised double-blind placebo-controlled cross-over study', Gut, vol. 71, pp. 1577-1587. https://doi.org/10.1136/gutjnl-2020-323297

APA

Koopen, A., Witjes, J., Wortelboer, K., Majait, S., Prodan, A., Levin, E., Herrema, H., Winkelmeijer, M., Aalvink, S., Bergman, J. J. G. H. M., Havik, S., Hartmann, B., Levels, H., Bergh, P-O., van Son, J., Balvers, M., Bastos, D. M., Stroes, E., Groen, A. K., ... Rampanelli, E. (2022). Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects: a randomised double-blind placebo-controlled cross-over study. Gut, 71, 1577-1587. https://doi.org/10.1136/gutjnl-2020-323297

Vancouver

Koopen A, Witjes J, Wortelboer K, Majait S, Prodan A, Levin E et al. Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects: a randomised double-blind placebo-controlled cross-over study. Gut. 2022;71:1577-1587. https://doi.org/10.1136/gutjnl-2020-323297

Author

Koopen, Annefleur ; Witjes, Julia ; Wortelboer, Koen ; Majait, Soumia ; Prodan, Andrei ; Levin, Evgeni ; Herrema, Hilde ; Winkelmeijer, Maaike ; Aalvink, Steven ; Bergman, Jacques J. G. H. M. ; Havik, Stephan ; Hartmann, Bolette ; Levels, Han ; Bergh, Per-Olof ; van Son, Jamie ; Balvers, Manon ; Bastos, Diogo Mendes ; Stroes, Erik ; Groen, Albert K. ; Henricsson, Marcus ; Kemper, Ellis Marleen ; Holst, Jens ; Strauch, Christopher M. ; Hazen, Stanley L. ; Backhed, Fredrik ; De Vos, Willem M. ; Nieuwdorp, Max ; Rampanelli, Elena. / Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects : a randomised double-blind placebo-controlled cross-over study. In: Gut. 2022 ; Vol. 71. pp. 1577-1587.

Bibtex

@article{1aa438145ef94aecb4358ea85b1d5c4f,
title = "Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects: a randomised double-blind placebo-controlled cross-over study",
abstract = "Objective Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS. Design In this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii/ placebo and underwent duodenal biopsies, mixed meal tests (6 hours postinfusion) and 24-hour continuous glucose monitoring. Results A. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B (REG1B)-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated. Conclusions A single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity.",
keywords = "diabetes mellitus, intestinal bacteria, duodenal mucosa, gut hormones, gene expression, INSULIN SENSITIVITY, INTESTINAL MICROBIOTA, PEPTIDE-1 SECRETION, GENE-EXPRESSION, BUTYRATE, MICE, OVEREXPRESSION, BACTERIA, GROWTH, WOMEN",
author = "Annefleur Koopen and Julia Witjes and Koen Wortelboer and Soumia Majait and Andrei Prodan and Evgeni Levin and Hilde Herrema and Maaike Winkelmeijer and Steven Aalvink and Bergman, {Jacques J. G. H. M.} and Stephan Havik and Bolette Hartmann and Han Levels and Per-Olof Bergh and {van Son}, Jamie and Manon Balvers and Bastos, {Diogo Mendes} and Erik Stroes and Groen, {Albert K.} and Marcus Henricsson and Kemper, {Ellis Marleen} and Jens Holst and Strauch, {Christopher M.} and Hazen, {Stanley L.} and Fredrik Backhed and {De Vos}, {Willem M.} and Max Nieuwdorp and Elena Rampanelli",
year = "2022",
doi = "10.1136/gutjnl-2020-323297",
language = "English",
volume = "71",
pages = "1577--1587",
journal = "Gut",
issn = "0017-5749",
publisher = "B M J Group",

}

RIS

TY - JOUR

T1 - Duodenal Anaerobutyricum soehngenii infusion stimulates GLP-1 production, ameliorates glycaemic control and beneficially shapes the duodenal transcriptome in metabolic syndrome subjects

T2 - a randomised double-blind placebo-controlled cross-over study

AU - Koopen, Annefleur

AU - Witjes, Julia

AU - Wortelboer, Koen

AU - Majait, Soumia

AU - Prodan, Andrei

AU - Levin, Evgeni

AU - Herrema, Hilde

AU - Winkelmeijer, Maaike

AU - Aalvink, Steven

AU - Bergman, Jacques J. G. H. M.

AU - Havik, Stephan

AU - Hartmann, Bolette

AU - Levels, Han

AU - Bergh, Per-Olof

AU - van Son, Jamie

AU - Balvers, Manon

AU - Bastos, Diogo Mendes

AU - Stroes, Erik

AU - Groen, Albert K.

AU - Henricsson, Marcus

AU - Kemper, Ellis Marleen

AU - Holst, Jens

AU - Strauch, Christopher M.

AU - Hazen, Stanley L.

AU - Backhed, Fredrik

AU - De Vos, Willem M.

AU - Nieuwdorp, Max

AU - Rampanelli, Elena

PY - 2022

Y1 - 2022

N2 - Objective Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS. Design In this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii/ placebo and underwent duodenal biopsies, mixed meal tests (6 hours postinfusion) and 24-hour continuous glucose monitoring. Results A. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B (REG1B)-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated. Conclusions A single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity.

AB - Objective Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS. Design In this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii/ placebo and underwent duodenal biopsies, mixed meal tests (6 hours postinfusion) and 24-hour continuous glucose monitoring. Results A. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B (REG1B)-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated. Conclusions A single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity.

KW - diabetes mellitus

KW - intestinal bacteria

KW - duodenal mucosa

KW - gut hormones

KW - gene expression

KW - INSULIN SENSITIVITY

KW - INTESTINAL MICROBIOTA

KW - PEPTIDE-1 SECRETION

KW - GENE-EXPRESSION

KW - BUTYRATE

KW - MICE

KW - OVEREXPRESSION

KW - BACTERIA

KW - GROWTH

KW - WOMEN

U2 - 10.1136/gutjnl-2020-323297

DO - 10.1136/gutjnl-2020-323297

M3 - Journal article

C2 - 34697034

VL - 71

SP - 1577

EP - 1587

JO - Gut

JF - Gut

SN - 0017-5749

ER -

ID: 286860371