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 - Bäckhed, Fredrik
AU - de Vos, Willem M.
AU - Nieuwdorp, Max
AU - Rampanelli, Elena
N1 - Publisher Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2022/8/1
Y1 - 2022/8/1
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. TRIAL REGISTRATION NUMBER: NTR-NL6630.
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. TRIAL REGISTRATION NUMBER: NTR-NL6630.
KW - diabetes mellitus
KW - duodenal mucosa
KW - gene expression
KW - gut hormones
KW - intestinal bacteria
UR - http://www.scopus.com/inward/record.url?scp=85134361224&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/gutjnl-2020-323297
DO - https://doi.org/10.1136/gutjnl-2020-323297
M3 - Article
C2 - 34697034
SN - 0017-5749
VL - 71
SP - 1577
EP - 1587
JO - Gut
JF - Gut
IS - 8
ER -