| 1. |
- Koopen, A., et al.
(författare)
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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
- 2022
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 71:8, s. 1577-1587
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Kootte, R. S., et al.
(författare)
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Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition
- 2017
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Ingår i: Cell Metabolism. - : Elsevier BV. - 1550-4131. ; 26:4, s. 611-619
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Tidskriftsartikel (refereegranskat)abstract
- The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own (autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition. We also observed changes in plasma metabolites such as gamma-aminobutyric acid and show that metabolic response upon allogenic FMT (defined as improved insulin sensitivity 6 weeks after FMT) is dependent on decreased fecal microbial diversity at baseline. In conclusion, the beneficial effects of lean donor FMT on glucose metabolism are associated with changes in intestinal microbiota and plasma metabolites and can be predicted based on baseline fecal microbiota composition.
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| 3. |
- Warmbrunn, M. V., et al.
(författare)
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Metabolite Profile of Treatment-Naive Metabolic Syndrome Subjects in Relation to Cardiovascular Disease Risk
- 2021
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 11:4
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic syndrome (MetSyn) is an important risk factor for type 2 diabetes and cardiovascular diseases (CVD). This study aimed to find distinct plasma metabolite profiles between insulin-resistant and non-insulin resistant subjects with MetSyn and evaluate if MetSyn metabolite profiles are related to CVD risk and lipid fluxes. In a cross-sectional study, untargeted metabolomics of treatment-naive males with MetSyn (n = 132) were analyzed together with clinical parameters. In a subset of MetSyn participants, CVD risk was calculated using the Framingham score (n = 111), and lipolysis (n = 39) was measured by a two-step hyperinsulinemic euglycemic clamp using [1,1,2,3,3-(2)H5] glycerol to calculate lipolysis suppression rates. Peripheral insulin resistance was related to fatty acid metabolism and glycerolphosphorylcholine. Interestingly, although insulin resistance is considered to be a risk factor for CVD, we observed that there was little correspondence between metabolites associated with insulin resistance and metabolites associated with CVD risk. The latter mainly belonged to the androgenic steroid, fatty acid, phosphatidylethanolamine, and phophatidylcholine pathways. These data provide new insights into metabolic changes in mild MetSyn pathophysiology and MetSyn CVD risk related to lipid metabolism. Prospective studies may focus on the pathophysiological role of the here-identified biomarkers.
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| 4. |
- Bakker, G. J., et al.
(författare)
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Oral vancomycin treatment does not alter markers of postprandial inflammation in lean and obese subjects
- 2019
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Ingår i: Physiological Reports. - : Wiley. - 2051-817X. ; 7:16
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Tidskriftsartikel (refereegranskat)abstract
- Intake of a high-fat meal induces a systemic inflammatory response in the postprandial which is augmented in obese subjects. However, the underlying mechanisms of this response have not been fully elucidated. We aimed to assess the effect of gut microbiota modulation on postprandial inflammatory response in lean and obese subjects. Ten lean and ten obese subjects with metabolic syndrome received oral vancomycin 500 mg four times per day for 7 days. Oral high-fat meal tests (50 g fat/m(2) body surface area) were performed before and after vancomycin intervention. Gut microbiota composition, leukocyte counts, plasma lipopolysaccharides (LPS), LPS-binding protein (LBP), IL-6 and MCP-1 concentrations and monocyte CCR2 and cytokine expression were determined before and after the high-fat meal. Oral vancomycin treatment resulted in profound changes in gut microbiota composition and significantly decreased bacterial diversity in both groups (phylogenetic diversity pre- versus post-intervention: lean, 56.9 +/- 7.8 vs. 21.4 +/- 6.6, P < 0.001; obese, 53.9 +/- 7.8 vs. 21.0 +/- 5.9, P < 0.001). After intervention, fasting plasma LPS significantly increased (lean, median [IQR] 0.81 [0.63-1.45] EU/mL vs. 2.23 [1.33-3.83] EU/mL, P = 0.017; obese, median [IQR] 0.76 [0.45-1.03] EU/mL vs. 1.44 [1.11-4.24], P = 0.014). However, postprandial increases in leukocytes and plasma LPS were unaffected by vancomycin in both groups. Moreover, we found no changes in plasma LBP, IL-6 and MCP-1 or in monocyte CCR2 expression. Despite major vancomycin-induced disruption of the gut microbiota and increased fasting plasma LPS, the postprandial inflammatory phenotype in lean and obese subjects was unaffected in this study.
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| 5. |
- Koopen, A. M., et al.
(författare)
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Plasma Metabolites Related to Peripheral and Hepatic Insulin Sensitivity Are Not Directly Linked to Gut Microbiota Composition
- 2020
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- Plasma metabolites affect a range of metabolic functions in humans, including insulin sensitivity (IS). A subset of these plasma metabolites is modified by the gut microbiota. To identify potential microbial-metabolite pathways involved in IS, we investigated the link between plasma metabolites, gut microbiota composition, and IS, using the gold-standard for peripheral and hepatic IS measurement in a group of participants with metabolic syndrome (MetSyn). In a cross-sectional study with 115 MetSyn participants, fasting plasma samples were collected for untargeted metabolomics analysis and fecal samples for 16S rRNA gene amplicon sequencing. A two-step hyperinsulinemic euglycemic clamp was performed to assess peripheral and hepatic IS. Collected data were integrated and potential interdependence between metabolites, gut microbiota, and IS was analyzed using machine learning prediction models. Plasma metabolites explained 13.2% and 16.7% of variance in peripheral and hepatic IS, respectively. Fecal microbiota composition explained 4.2% of variance in peripheral IS and was not related to hepatic IS. Although metabolites could partially explain the variances in IS, the top metabolites related to peripheral and hepatic IS did not significantly correlate with gut microbiota composition (both on taxonomical level and alpha-diversity). However, all plasma metabolites could explain 18.5% of the variance in microbial alpha-diversity (Shannon); the top 20 metabolites could even explain 44.5% of gut microbial alpha-diversity. In conclusion, plasma metabolites could partially explain the variance in peripheral and hepatic IS; however, these metabolites were not directly linked to the gut microbiota composition, underscoring the intricate relation between plasma metabolites, the gut microbiota, and IS in MetSyn
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