Adipose tissue; Dysosmobacter welbionis J115T; Glucose tolerance; Gut microbiota; Metformin; Obesity; Prebiotics; Type 2 diabetes; Humans; Animals; Mice; Obesity/drug therapy; Diet, High-Fat; Metformin/therapeutic use; Metformin/pharmacology; Diabetes Mellitus, Type 2/drug therapy; Clostridiales; Diabetes Mellitus, Type 2; Dysosmobacter welbionis; Internal Medicine; Endocrinology, Diabetes and Metabolism
Abstract :
[en] [en] AIMS/HYPOTHESIS: We aimed to investigate the association between the abundance of Dysosmobacter welbionis, a commensal gut bacterium, and metabolic health in human participants with obesity and diabetes, and the influence of metformin treatment and prebiotic intervention.
METHODS: Metabolic variables were assessed and faecal samples were collected from 106 participants in a randomised controlled intervention with a prebiotic stratified by metformin treatment (Food4Gut trial). The abundance of D. welbionis was measured by quantitative PCR and correlated with metabolic markers. The in vitro effect of metformin on D. welbionis growth was evaluated and an in vivo study was performed in mice to investigate the effects of metformin and D. welbionis J115T supplementation, either alone or in combination, on metabolic variables.
RESULTS: D. welbionis abundance was unaffected by prebiotic treatment but was significantly higher in metformin-treated participants. Responders to prebiotic treatment had higher baseline D. welbionis levels than non-responders. D. welbionis was negatively correlated with aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and fasting blood glucose levels in humans with obesity and type 2 diabetes. In vitro, metformin had no direct effect on D. welbionis growth. In mice, D. welbionis J115T treatment reduced body weight gain and liver weight, and improved glucose tolerance to a better level than metformin, but did not have synergistic effects with metformin.
CONCLUSIONS/INTERPRETATION: D. welbionis abundance is influenced by metformin treatment and associated with prebiotic response, liver health and glucose metabolism in humans with obesity and diabetes. This study suggests that D. welbionis may play a role in metabolic health and warrants further investigation.
CLINICAL TRIAL: NCT03852069.
Disciplines :
Endocrinology, metabolism & nutrition
Author, co-author :
Moens de Hase, Emilie; Metabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain (Université catholique de Louvain), Brussels, Belgium ; WELBIO-Walloon Excellence in Life Sciences and Biotechnology, WELBIO Department, WEL Research Institute, Wavre, Belgium
Neyrinck, Audrey M ; Metabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain (Université catholique de Louvain), Brussels, Belgium
Rodriguez, Julie ; Metabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain (Université catholique de Louvain), Brussels, Belgium
Cnop, Miriam ; ULB Center for Diabetes Research, Université Libre de Bruxelles, and Division of Endocrinology, Erasmus Hospital, Brussels, Belgium
Paquot, Nicolas ; Université de Liège - ULiège > Département des sciences cliniques > Diabétologie, nutrition et maladies métaboliques
Thissen, Jean-Paul ; Pole of Endocrinology, Diabetes and Nutrition, Institute of Experimental and Clinical Research (IREC), UCLouvain (Université catholique de Louvain), Brussels, Belgium
Xu, Yining; Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute (LDRI), UCLouvain (Université catholique de Louvain), Brussels, Belgium
Beloqui, Ana ; WELBIO-Walloon Excellence in Life Sciences and Biotechnology, WELBIO Department, WEL Research Institute, Wavre, Belgium ; Advanced Drug Delivery and Biomaterials, Louvain Drug Research Institute (LDRI), UCLouvain (Université catholique de Louvain), Brussels, Belgium
Bindels, Laure B ; Metabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain (Université catholique de Louvain), Brussels, Belgium ; WELBIO-Walloon Excellence in Life Sciences and Biotechnology, WELBIO Department, WEL Research Institute, Wavre, Belgium
Delzenne, Nathalie M ; Metabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain (Université catholique de Louvain), Brussels, Belgium
Van Hul, Matthias ; Metabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain (Université catholique de Louvain), Brussels, Belgium. Matthias.vanhul@uclouvain.be ; WELBIO-Walloon Excellence in Life Sciences and Biotechnology, WELBIO Department, WEL Research Institute, Wavre, Belgium. Matthias.vanhul@uclouvain.be
Cani, Patrice D ; Metabolism and Nutrition Research Group, Louvain Drug Research Institute (LDRI), UCLouvain (Université catholique de Louvain), Brussels, Belgium. patrice.cani@uclouvain.be ; WELBIO-Walloon Excellence in Life Sciences and Biotechnology, WELBIO Department, WEL Research Institute, Wavre, Belgium. patrice.cani@uclouvain.be ; Institute of Experimental and Clinical Research (IREC), UCLouvain (Université catholique de Louvain), Brussels, Belgium. patrice.cani@uclouvain.be
Language :
English
Title :
Impact of metformin and Dysosmobacter welbionis on diet-induced obesity and diabetes: from clinical observation to preclinical intervention.
Publication date :
February 2024
Journal title :
Diabetologia
ISSN :
0012-186X
eISSN :
1432-0428
Publisher :
Springer Science and Business Media Deutschland GmbH, Germany
SPW - Service Public de Wallonie [BE] La Caixa Foundation [ES] F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Funding text :
Food4Gut was supported by the competitive cluster Wagralim from Wallonia (Food4Gut 518 project, convention 1318148). NMD is a recipient of grants from the Fonds de la Recherche Scientifique (FRS-FNRS, convention PINT-MULTI R.8013.19 [NEURON, call 2019] and convention PDR T.0068.19). PDC is a recipient of grants from the FNRS (Projet de Recherche PDR-convention: FNRS T.0030.21, CDR-convention: J.0027.22, FRFS-WELBIO: WELBIO-CR-2022A-02, EOS: program no. 40007505), ARC (Action de recherche concertée: ARC19/24-096) and La Caixa (NeuroGut). The study funders were not involved in the design of the study; the collection, analysis and interpretation of data; or writing of the report; and did not impose any restrictions regarding the publication of the report. Action de Recherche Concertée
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