28 results on '"Scheithauer, Torsten P."'
Search Results
2. Glucose-mediated insulin secretion is improved in FHL2-deficient mice and elevated FHL2 expression in humans is associated with type 2 diabetes
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Habibe, Jayron J., Clemente-Olivo, Maria P., Scheithauer, Torsten P. M., Rampanelli, Elena, Herrema, Hilde, Vos, Mariska, Mieremet, Arnout, Nieuwdorp, Max, van Raalte, Daniel H., Eringa, Etto C., and de Vries, Carlie J. M. more...
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- 2022
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3. Gut virome profiling identifies a widespread bacteriophage family associated with metabolic syndrome
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de Jonge, Patrick A., Wortelboer, Koen, Scheithauer, Torsten P. M., van den Born, Bert-Jan H., Zwinderman, Aeilko H., Nobrega, Franklin L., Dutilh, Bas E., Nieuwdorp, Max, and Herrema, Hilde
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- 2022
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4. Faecal Microbiota transplantation affects liver DNA methylation in Non-alcoholic fatty liver disease:a multi-omics approach
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Stols-Gonçalves, Daniela, Mak, Anne Linde, Madsen, Mette S., van der Vossen, Eduard W. J., Bruinstroop, Eveline, Henneman, Peter, Mol, Femke, Scheithauer, Torsten P. M., Smits, Loek, Witjes, Julia, Meijnikman, Abraham Stijn, Verheij, Joanne, Nieuwdorp, Max, Holleboom, Adriaan G., and Levin, Evgeni more...
- Abstract
Individuals with nonalcoholic fatty liver disease (NAFLD) have an altered gut microbiota composition. Moreover, hepatic DNA methylation may be altered in the state of NAFLD. Using a fecal microbiota transplantation (FMT) intervention, we aimed to investigate whether a change in gut microbiota composition relates to altered liver DNA methylation in NAFLD. Moreover, we assessed whether plasma metabolite profiles altered by FMT relate to changes in liver DNA methylation. Twenty-one individuals with NAFLD underwent three 8-weekly vegan allogenic donor (n = 10) or autologous (n = 11) FMTs. We obtained hepatic DNA methylation profiles from paired liver biopsies of study participants before and after FMTs. We applied a multi-omics machine learning approach to identify changes in the gut microbiome, peripheral blood metabolome and liver DNA methylome, and analyzed cross-omics correlations. Vegan allogenic donor FMT compared to autologous FMT induced distinct differential changes in I) gut microbiota profiles, including increased abundance of Eubacterium siraeum and potential probiotic Blautia wexlerae; II) plasma metabolites, including altered levels of phenylacetylcarnitine (PAC) and phenylacetylglutamine (PAG) both from gut-derived phenylacetic acid, and of several choline-derived long-chain acylcholines; and III) hepatic DNA methylation profiles, most importantly in Threonyl-TRNA Synthetase 1 (TARS) and Zinc finger protein 57 (ZFP57). Multi-omics analysis showed that Gemmiger formicillis and Firmicutes bacterium_CAG_170 positively correlated with both PAC and PAG. E siraeum negatively correlated with DNA methylation of cg16885113 in ZFP57. Alterations in gut microbiota composition by FMT caused widespread changes in plasma metabolites (e.g. PAC, PAG, and choline-derived metabolites) and liver DNA methylation profiles in individuals with NAFLD. These results indicate that FMTs might induce metaorganismal pathway changes, from the gut bacteria to the liver. more...
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- 2023
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5. Faecal Microbiota transplantation affects liver DNA methylation in Non-alcoholic fatty liver disease: a multi-omics approach
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Stols-Gonçalves, Daniela, primary, Mak, Anne Linde, additional, Madsen, Mette S., additional, van der Vossen, Eduard W. J., additional, Bruinstroop, Eveline, additional, Henneman, Peter, additional, Mol, Femke, additional, Scheithauer, Torsten P. M., additional, Smits, Loek, additional, Witjes, Julia, additional, Meijnikman, Abraham Stijn, additional, Verheij, Joanne, additional, Nieuwdorp, Max, additional, Holleboom, Adriaan G., additional, and Levin, Evgeni, additional more...
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- 2023
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6. Gut virome profiling identifies a widespread bacteriophage family associated with metabolic syndrome
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de Jonge, Patrick A, Wortelboer, Koen, Scheithauer, Torsten P M, van den Born, Bert-Jan H, Zwinderman, Aeilko H, Nobrega, Franklin L, Dutilh, Bas E, Nieuwdorp, Max, Herrema, Hilde, de Jonge, Patrick A, Wortelboer, Koen, Scheithauer, Torsten P M, van den Born, Bert-Jan H, Zwinderman, Aeilko H, Nobrega, Franklin L, Dutilh, Bas E, Nieuwdorp, Max, and Herrema, Hilde more...
- Abstract
There is significant interest in altering the course of cardiometabolic disease development via gut microbiomes. Nevertheless, the highly abundant phage members of the complex gut ecosystem -which impact gut bacteria- remain understudied. Here, we show gut virome changes associated with metabolic syndrome (MetS), a highly prevalent clinical condition preceding cardiometabolic disease, in 196 participants by combined sequencing of bulk whole genome and virus like particle communities. MetS gut viromes exhibit decreased richness and diversity. They are enriched in phages infecting Streptococcaceae and Bacteroidaceae and depleted in those infecting Bifidobacteriaceae. Differential abundance analysis identifies eighteen viral clusters (VCs) as significantly associated with either MetS or healthy viromes. Among these are a MetS-associated Roseburia VC that is related to healthy control-associated Faecalibacterium and Oscillibacter VCs. Further analysis of these VCs revealed the Candidatus Heliusviridae, a highly widespread gut phage lineage found in 90+% of participants. The identification of the temperate Ca. Heliusviridae provides a starting point to studies of phage effects on gut bacteria and the role that this plays in MetS. more...
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- 2022
7. Gut virome profiling identifies a widespread bacteriophage family associated with metabolic syndrome
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Theoretical Biology and Bioinformatics, Sub Bioinformatics, de Jonge, Patrick A, Wortelboer, Koen, Scheithauer, Torsten P M, van den Born, Bert-Jan H, Zwinderman, Aeilko H, Nobrega, Franklin L, Dutilh, Bas E, Nieuwdorp, Max, Herrema, Hilde, Theoretical Biology and Bioinformatics, Sub Bioinformatics, de Jonge, Patrick A, Wortelboer, Koen, Scheithauer, Torsten P M, van den Born, Bert-Jan H, Zwinderman, Aeilko H, Nobrega, Franklin L, Dutilh, Bas E, Nieuwdorp, Max, and Herrema, Hilde more...
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- 2022
8. Fecal microbiota transplantation does not alter bacterial translocation and visceral adipose tissue inflammation in individuals with obesity
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Bakker, Guido J., primary, Meijnikman, Abraham S., additional, Scheithauer, Torsten P., additional, Davids, Mark, additional, Aydin, Ömrüm, additional, Boerlage, Thomas C. C., additional, Brauw, L. Maurits, additional, Laar, Arnold W., additional, Gerdes, Victor E., additional, Groen, Albert K., additional, Raalte, Daniël H., additional, Herrema, Hilde, additional, and Nieuwdorp, Max, additional more...
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- 2021
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9. Effect of Fecal Microbiota Transplantation Combined With Mediterranean Diet on Insulin Sensitivity in Subjects With Metabolic Syndrome
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Koopen, Annefleur M., primary, Almeida, Eduardo L., additional, Attaye, Ilias, additional, Witjes, Julia J., additional, Rampanelli, Elena, additional, Majait, Soumia, additional, Kemper, Marleen, additional, Levels, Johannes H. M., additional, Schimmel, Alinda W. M., additional, Herrema, Hilde, additional, Scheithauer, Torsten P. M., additional, Frei, Werner, additional, Dragsted, Lars, additional, Hartmann, Bolette, additional, Holst, Jens J., additional, O’Toole, Paul W., additional, Groen, Albert K., additional, and Nieuwdorp, Max, additional more...
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- 2021
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10. Bacteriophages from treatment-naïve type 2 diabetes individuals drive an inflammatory response in human co-cultures of dendritic cells and T cells
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Scheithauer, Torsten P. M., Wortelboer, Koen, Winkelmeijer, Maaike, Verdoes, Xanthe, Aydin, Ömrüm, Acherman, Yair I. Z., de Brauw, Maurits L., Nieuwdorp, Max, Rampanelli, Elena, de Jonge, Patrick A., and Herrema, Hilde more...
- Abstract
ABSTRACTIndividuals with type 2 diabetes (T2D) show signs of low-grade inflammation, which is related to the development of insulin resistance and beta-cell dysfunction. However, the underlying triggers remain unknown. The gut microbiota is a plausible source as it comprises pro-inflammatory bacteria, bacterial metabolites and viruses, including (bacterio)phages. These prokaryotic viruses have been shown to mediate inflammatory responses in gastrointestinal disease. Given the differences in phage populations in healthy individuals versus those with cardiometabolic diseases such as T2D, we here questioned whether phages from T2D individuals would have increased immunogenic potential. To address this, we isolated intestinal phages from a fresh stool sample of healthy controls and individuals with newly diagnosed, treatment-naive T2D. Phages were purified using cesium chloride ultracentrifugation and incubated with healthy donor dendritic cells (DCs) and autologous T cells. Donors with T2D had slightly higher free viral particle numbers compared to healthy controls (p = .1972), which has been previously associated with disease states. Further, phages from T2D induced a higher inflammatory response in DCs and T cells than phages from HC. For example, the expression of the co-stimulatory molecule CD86 on DCs (p < .001) and interferon-y secretion from T cells (p < .01) were increased when comparing the two groups. These results suggest that phages might play a role in low-grade inflammation in T2D individuals. more...
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- 2024
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11. Gut microbe–host interactions in post-COVID syndrome: a debilitating or restorative partnership?
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Scheithauer, Torsten P. M., Montijn, Roy C., and Mieremet, Arnout
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ABSTRACTPost-COVID syndrome (PCS) patients have reported a wide range of symptoms, including fatigue, shortness of breath, and diarrhea. Particularly, the presence of gastrointestinal symptoms has led to the hypothesis that the gut microbiome is involved in the development and severity of PCS. The objective of this review is to provide an overview of the role of the gut microbiome in PCS by describing the microbial composition and microbial metabolites in COVID-19 and PCS. Moreover, host–microbe interactions via the microbiota-gut-brain (MGB) and the microbiota-gut-lung (MGL) axes are described. Furthermore, we explore the potential of therapeutically targeting the gut microbiome to support the recovery of PCS by reviewing preclinical model systems and clinical studies. Overall, current studies provide evidence that the gut microbiota is affected in PCS; however, diversity in symptoms and highly individual microbiota compositions suggest the need for personalized medicine. Gut-targeted therapies, including treatments with pre- and probiotics, have the potential to improve the quality of life of affected individuals. more...
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- 2024
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12. Effect of fecal microbiota transplantation combined with Mediterranean diet on insulin sensitivity in subjects with metabolic syndrome
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Koopen, Annefleur M, Almeida, Eduardo L., Attaye, Ilias, Witjes, Julia J, Rampanelli, Elena, Majait, Soumia, Kemper, Marleen, Levels, Johannes H M, Schimmel, Alinda W M, Herrema, Hilde, Scheithauer, Torsten P M, Frei, Werner, Dragsted, Lars Ove, Hartmann, Bolette, Holst, Jens Juul, O’Toole, Paul W, Groen, Albert K, Nieuwdorp, Max, Koopen, Annefleur M, Almeida, Eduardo L., Attaye, Ilias, Witjes, Julia J, Rampanelli, Elena, Majait, Soumia, Kemper, Marleen, Levels, Johannes H M, Schimmel, Alinda W M, Herrema, Hilde, Scheithauer, Torsten P M, Frei, Werner, Dragsted, Lars Ove, Hartmann, Bolette, Holst, Jens Juul, O’Toole, Paul W, Groen, Albert K, and Nieuwdorp, Max more...
- Abstract
Background: Recent studies demonstrate that a Mediterranean diet has beneficial metabolic effects in metabolic syndrome subjects. Since we have shown that fecal microbiota transplantation (FMT) from lean donors exerts beneficial effects on insulin sensitivity, in the present trial, we investigated the potential synergistic effects on insulin sensitivity of combining a Mediterranean diet with donor FMT in subjects with metabolic syndrome. Design: Twenty-four male subjects with metabolic syndrome were put on a Mediterranean diet and after a 2-week run-in phase, the subjects were randomized to either lean donor (n = 12) or autologous (n = 12) FMT. Changes in the gut microbiota composition and bacterial strain engraftment after the 2-week dietary regimens and 6 weeks post-FMT were the primary endpoints. The secondary objectives were changes in glucose fluxes (both hepatic and peripheral insulin sensitivity), postprandial plasma incretin (GLP-1) levels, subcutaneous adipose tissue inflammation, and plasma metabolites. Results: Consumption of the Mediterranean diet resulted in a reduction in body weight, HOMA-IR, and lipid levels. However, no large synergistic effects of combining the diet with lean donor FMT were seen on the gut microbiota diversity after 6 weeks. Although we did observe changes in specific bacterial species and plasma metabolites, no significant beneficial effects on glucose fluxes, postprandial incretins, or subcutaneous adipose tissue inflammation were detected. Conclusions: In this small pilot randomized controlled trial, no synergistic beneficial metabolic effects of combining a Mediterranean diet with lean donor FMT on glucose metabolism were achieved. However, we observed engraftment of specific bacterial species. Future trials are warranted to test the combination of other microbial interventions and diets in metabolic syndrome. more...
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- 2021
13. Compensatory intestinal immunoglobulin response after vancomycin treatment in humans
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Scheithauer, Torsten P. M., primary, Bakker, Guido J., additional, Winkelmeijer, Maaike, additional, Davids, Mark, additional, Nieuwdorp, Max, additional, van Raalte, Daniël H., additional, and Herrema, Hilde, additional more...
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- 2021
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14. Gut Microbiota as a Trigger for Metabolic Inflammation in Obesity and Type 2 Diabetes
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Scheithauer, Torsten P. M., primary, Rampanelli, Elena, additional, Nieuwdorp, Max, additional, Vallance, Bruce A., additional, Verchere, C. Bruce, additional, van Raalte, Daniël H., additional, and Herrema, Hilde, additional more...
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- 2020
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15. Fecal microbiota transplantation does not alter bacterial translocation and visceral adipose tissue inflammation in individuals with obesity.
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Bakker, Guido J., Meijnikman, Abraham S., Scheithauer, Torsten P., Davids, Mark, Aydin, Ömrüm, Boerlage, Thomas C. C., de Brauw, L. Maurits, van de Laar, Arnold W., Gerdes, Victor E., Groen, Albert K., van Raalte, Daniël H., Herrema, Hilde, and Nieuwdorp, Max more...
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FECAL microbiota transplantation ,ADIPOSE tissues ,TYPE 2 diabetes ,BACTERIAL DNA ,OBESITY ,BODY mass index ,BARIATRIC surgery - Abstract
Aims: Visceral adipose tissue inflammation is a fundamental mechanism of insulin resistance in obesity and type 2 diabetes. Translocation of intestinal bacteria has been suggested as a driving factor for the inflammation. However, although bacterial DNA was detected in visceral adipose tissue of humans with obesity, it is unclear to what extent this is contamination or whether the gut microbiota is causally involved. Effects of fecal microbiota transplantation (FMT) on bacterial translocation and visceral adipose tissue inflammation in individuals with obesity and insulin resistance were assessed. Material and Methods: Eight individuals with clinically severe obesity (body mass index [BMI] >35 kg/m2) and metabolic syndrome received lean donor FMT 4 weeks prior to elective bariatric surgery. The participants were age‐, sex‐, and BMI‐matched to 16 controls that underwent no fecal transplantation. Visceral adipose tissue was collected during surgery. Bacterial translocation was assessed by 16S rRNA gene sequencing of adipose tissue and feces. Pro‐inflammatory cytokine expression and histopathological analyses of visceral adipose tissue were performed to assess inflammation. Results: Fecal microbiota transplantation significantly altered gut microbiota composition. Visceral adipose tissue contained a very low quantity of bacterial DNA in both groups. No difference in visceral bacterial DNA content between groups was observed. Also, visceral expression of pro‐inflammatory cytokines and macrophage infiltration did not differ between groups. No correlation between inflammatory tone and bacterial translocation was observed. Conclusions: Visceral bacterial DNA content and level of inflammation were not altered upon FMT. Thus, bacterial translocation may not be the main driver of visceral adipose tissue inflammation in obesity. [ABSTRACT FROM AUTHOR] more...
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- 2022
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16. Gut-derived bacterial flagellin induces beta-cell inflammation and dysfunction.
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Scheithauer, Torsten P. M., Herrema, Hilde, Hongbing Yu, Bakker, Guido J., Winkelmeijer, Maaike, Soukhatcheva, Galina, Dai, Derek, Ma, Caixia, Havik, Stefan R., Balvers, Manon, Davids, Mark, Meijnikman, Abraham S., Aydin, Ömrüm, van den Born, Bert-Jan H., Besselink, Marc G., Busch, Olivier R., de Brauw, Maurits, van de Laar, Arnold, Belzer, Clara, and Stahl, Martin more...
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- 2022
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17. Compensatory intestinal antibody response against pro-inflammatory microbiota after bariatric surgery.
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Scheithauer, Torsten P. M., Davids, Mark, Winkelmeijer, Maaike, Verdoes, Xanthe, Aydin, Ömrüm, de Brauw, Maurits, van de Laar, Arnold, Meijnikman, Abraham S., Gerdes, Victor E. A., van Raalte, Daniël, Herrema, Hilde, and Nieuwdorp, Max more...
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- 2022
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18. Oral vancomycin treatment does not alter markers of postprandial inflammation in lean and obese subjects
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Bakker, Guido J., primary, Schnitzler, Johan G., additional, Bekkering, Siroon, additional, Clercq, Nicolien C., additional, Koopen, Annefleur M., additional, Hartstra, Annick V., additional, Meessen, Emma C. E., additional, Scheithauer, Torsten P., additional, Winkelmeijer, Maaike, additional, Dallinga‐Thie, Geesje M., additional, Cani, Patrice D., additional, Kemper, Elles Marleen, additional, Soeters, Maarten R., additional, Kroon, Jeffrey, additional, Groen, Albert K., additional, Raalte, Daniël H., additional, Herrema, Hilde, additional, and Nieuwdorp, Max, additional more...
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- 2019
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19. Pancreatic 18F-FDG uptake is increased in type 2 diabetes patients compared to non-diabetic controls
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Bakker, Guido J., primary, Vanbellinghen, Manon C., additional, Scheithauer, Torsten P., additional, Verchere, C. Bruce, additional, Stroes, Erik S., additional, Timmers, Nyanza K. L. M., additional, Herrema, Hilde, additional, Nieuwdorp, Max, additional, Verberne, Hein J., additional, and van Raalte, Daniël H., additional more...
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- 2019
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20. Oral vancomycin treatment does not alter markers of postprandial inflammation in lean and obese subjects.
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UCL - SSS/LDRI - Louvain Drug Research Institute, Bakker, Guido J, Schnitzler, Johan G, Bekkering, Siroon, de Clercq, Nicolien C, Koopen, Annefleur M, Hartstra, Annick V, Meessen, Emma C E, Scheithauer, Torsten P, Winkelmeijer, Maaike, Dallinga-Thie, Geesje M, Cani, Patrice D., Kemper, Elles Marleen, Soeters, Maarten R, Kroon, Jeffrey, Groen, Albert K, van Raalte, Daniël H, Herrema, Hilde, Nieuwdorp, Max, UCL - SSS/LDRI - Louvain Drug Research Institute, Bakker, Guido J, Schnitzler, Johan G, Bekkering, Siroon, de Clercq, Nicolien C, Koopen, Annefleur M, Hartstra, Annick V, Meessen, Emma C E, Scheithauer, Torsten P, Winkelmeijer, Maaike, Dallinga-Thie, Geesje M, Cani, Patrice D., Kemper, Elles Marleen, Soeters, Maarten R, Kroon, Jeffrey, Groen, Albert K, van Raalte, Daniël H, Herrema, Hilde, and Nieuwdorp, Max more...
- 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 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. more...
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- 2019
21. Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study
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de Groot, Pieter F., primary, Belzer, Clara, additional, Aydin, Ömrüm, additional, Levin, Evgeni, additional, Levels, Johannes H., additional, Aalvink, Steven, additional, Boot, Fransje, additional, Holleman, Frits, additional, van Raalte, Daniël H., additional, Scheithauer, Torsten P., additional, Simsek, Suat, additional, Schaap, Frank G., additional, Olde Damink, Steven W. M., additional, Roep, Bart O., additional, Hoekstra, Joost B., additional, de Vos, Willem M., additional, and Nieuwdorp, Max, additional more...
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- 2017
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22. Pancreatic 18F-FDG uptake is increased in type 2 diabetes patients compared to non-diabetic controls.
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Bakker, Guido J., Vanbellinghen, Manon C., Scheithauer, Torsten P., Verchere, C. Bruce, Stroes, Erik S., Timmers, Nyanza K. L. M., Herrema, Hilde, Nieuwdorp, Max, Verberne, Hein J., and van Raalte, Daniël H. more...
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PANCREATIC beta cells ,TYPE 2 diabetes ,PANCREAS ,PEOPLE with diabetes - Abstract
Introduction: Increasing evidence indicates that the development of type 2 diabetes is driven by chronic low grade beta-cell inflammation. However, it is unclear whether pancreatic inflammation can be noninvasively visualized in type 2 diabetes patients. We aimed to assess pancreatic
18 F-FDG uptake in type 2 diabetes patients and controls using18 F-fluorodeoxylglucose positron emission tomography/computed tomography (18 F-FDG PET/CT). Material and methods: In this retrospective cross-sectional study, we enrolled 20 type 2 diabetes patients and 65 controls who had undergone a diagnostic18 F-FDG PET/CT scan and obtained standardized uptake values (SUVs) of pancreas and muscle. Pancreatic SUV was adjusted for background uptake in muscle and for fasting blood glucose concentrations. Results: The maximum pancreatic SUVs adjusted for background muscle uptake (SUVmax.m ) and fasting blood glucose concentration (SUVglucose ) were significantly higher in diabetes patients compared to controls (median 2.86 [IQR 2.24–4.36] compared to 2.15 [IQR 1.51–2.83], p = 0.006 and median 2.76 [IQR 1.18–4.34] compared to 1.91 [IQR 1.27–2.55], p<0.001, respectively). In linear regression adjusting for age and body mass index, diabetes remained the main predictor of SUVmax.m and SUVglucose . Conclusion: Pancreatic18 F-FDG uptake adjusted for background muscle uptake and fasting blood glucose concentration was significantly increased in type 2 diabetes patients. [ABSTRACT FROM AUTHOR] more...- Published
- 2019
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23. Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study
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De Groot, Pieter F., Belzer, Clara, Aydin, Ömrüm, Levin, Evgeni, Levels, Johannes H., Aalvink, Steven, Boot, Fransje, Holleman, Frits, Van Raalte, Daniël H., Scheithauer, Torsten P., Simsek, Suat, Schaap, Frank G., Olde Damink, Steven W.M., Roep, Bart O., Hoekstra, Joost B., De Vos, Willem M., Nieuwdorp, Max, De Groot, Pieter F., Belzer, Clara, Aydin, Ömrüm, Levin, Evgeni, Levels, Johannes H., Aalvink, Steven, Boot, Fransje, Holleman, Frits, Van Raalte, Daniël H., Scheithauer, Torsten P., Simsek, Suat, Schaap, Frank G., Olde Damink, Steven W.M., Roep, Bart O., Hoekstra, Joost B., De Vos, Willem M., and Nieuwdorp, Max more...
- Abstract
Objective: Environmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production of short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy controls (HC) is lacking. Research design and methods: We included 53 T1D patients without complications or medication and 50 HC matched for age, sex and BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade systemic inflammation were measured. Results: Oral microbiota were markedly different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis showed decreased butyrate producing species in T1D and less butyryl-CoA transferase genes. Also, plasma levels of acetate and propionate were lower in T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and Subdoligranulum correlated with glycemic control, inflammatory parameters and SCFA. Conclusions: We conclude that T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels. Future research should disentangle cause and effect and whether supplementation of SCFA-producing bacteria or SCFA alone can have disease-modifying effects in T1D. more...
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- 2017
24. Donor metabolic characteristics drive effects of faecal microbiota transplantation on recipient insulin sensitivity, energy expenditure and intestinal transit time
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de Groot, Pieter, Scheithauer, Torsten, Bakker, Guido J, Prodan, Andrei, Levin, Evgeni, Khan, Muhammad Tanweer, Herrema, Hilde, Ackermans, Mariette, Serlie, Mireille J M, de Brauw, Maurits, Levels, Johannes H M, Sales, Amber, Gerdes, Victor E, Ståhlman, Marcus, Schimmel, Alinda W M, Dallinga-Thie, Geesje, Bergman, Jacques JGHM, Holleman, Frits, Hoekstra, Joost B L, Groen, Albert, Ba¨ckhed, Fredrik, and Nieuwdorp, Max more...
- Abstract
ObjectiveBariatric surgery improves glucose metabolism. Recent data suggest that faecal microbiota transplantation (FMT) using faeces from postbariatric surgery diet-induced obese mice in germ-free mice improves glucose metabolism and intestinal homeostasis. We here investigated whether allogenic FMT using faeces from post-Roux-en-Y gastric bypass donors (RYGB-D) compared with using faeces from metabolic syndrome donors (METS-D) has short-term effects on glucose metabolism, intestinal transit time and adipose tissue inflammation in treatment-nai¨ve, obese, insulin-resistant male subjects.DesignSubjects with metabolic syndrome (n=22) received allogenic FMT either from RYGB-D or METS-D. Hepatic and peripheral insulin sensitivity as well as lipolysis were measured at baseline and 2 weeks after FMT by hyperinsulinaemic euglycaemic stable isotope (2H2-glucose and 2H5-glycerol) clamp. Secondary outcome parameters were changes in resting energy expenditure, intestinal transit time, faecal short-chain fatty acids (SCFA) and bile acids, and inflammatory markers in subcutaneous adipose tissue related to intestinal microbiota composition. Faecal SCFA, bile acids, glycaemic control and inflammatory parameters were also evaluated at 8 weeks.ResultsWe observed a significant decrease in insulin sensitivity 2 weeks after allogenic METS-D FMT (median rate of glucose disappearance: from 40.6 to 34.0 µmol/kg/min; p<0.01). Moreover, a trend (p=0.052) towards faster intestinal transit time following RYGB-D FMT was seen. Finally, we observed changes in faecal bile acids (increased lithocholic, deoxycholic and (iso)lithocholic acid after METS-D FMT), inflammatory markers (decreased adipose tissue chemokine ligand 2 (CCL2) gene expression and plasma CCL2 after RYGB-D FMT) and changes in several intestinal microbiota taxa.ConclusionAllogenic FMT using METS-D decreases insulin sensitivity in metabolic syndrome recipients when compared with using post-RYGB-D. Further research is needed to delineate the role of donor characteristics in FMT efficacy in human insulin-resistant subjects.Trial registration numberNTR4327. more...
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- 2020
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25. Causality of small and large intestinal microbiota in weight regulation and insulin resistance.
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Scheithauer, Torsten P.M., Dallinga-Thie, Geesje M., de Vos, Willem M., Nieuwdorp, Max, and van Raalte, Daniël H.
- Abstract
Objective The twin pandemics of obesity and Type 2 diabetes (T2D) are a global challenge for health care systems. Changes in the environment, behavior, diet, and lifestyle during the last decades are considered the major causes. A Western diet, which is rich in saturated fat and simple sugars, may lead to changes in gut microbial composition and physiology, which have recently been linked to the development of metabolic diseases. Methods We will discuss evidence that demonstrates the influence of the small and large intestinal microbiota on weight regulation and the development of insulin resistance, based on literature search. Results Altered large intestinal microbial composition may promote obesity by increasing energy harvest through specialized gut microbes. In both large and small intestine, microbial alterations may increase gut permeability that facilitates the translocation of whole bacteria or endotoxic bacterial components into metabolic active tissues. Moreover, changed microbial communities may affect the production of satiety-inducing signals. Finally, bacterial metabolic products, such as short chain fatty acids (SCFAs) and their relative ratios, may be causal in disturbed immune and metabolic signaling, notably in the small intestine where the surface is large. The function of these organs (adipose tissue, brain, liver, muscle, pancreas) may be disturbed by the induction of low-grade inflammation, contributing to insulin resistance. Conclusions Interventions aimed to restoring gut microbial homeostasis, such as ingestion of specific fibers or therapeutic microbes, are promising strategies to reduce insulin resistance and the related metabolic abnormalities in obesity, metabolic syndrome, and type 2 diabetes. This article is part of a special issue on microbiota. [ABSTRACT FROM AUTHOR] more...
- Published
- 2016
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26. The histamine H4receptor is a potent inhibitor of adhesion‐dependent degranulation in human neutrophils
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Dib, Karim, Perecko, Tomas, Jenei, Veronika, McFarlane, Cheryl, Comer, David, Brown, Vanessa, Katebe, Mwape, Scheithauer, Torsten, Thurmond, Robin L., Chazot, Paul L., and Ennis, Madeleine
- Abstract
The presence of a functional histamine H4 receptor in neutrophils with anti‐inflammatory properties. The histamine H4receptor regulates the inflammatory response. However, it is not known whether this receptor has a functional role in human neutrophils. We found that fMLP (1 μM), but not histamine (0.1–1 μM), induced Mac‐1‐dependent adhesion, polarization, and degranulation (release of lactoferrin). A pretreatment of neutrophils with histamine (0.001–1 μM) or JNJ 28610244 (0.1–10 μM), a specific H4receptor agonist, led to inhibition of degranulation. Total inhibition of degranulation was obtained with 0.1 μM histamine and 10 μM JNJ 28610244. Furthermore, such inhibition by histamine of degranulation was reversed by JNJ 7777120 and JNJ 28307474, two selective H4receptor antagonists. However, neither histamine nor the H4receptor agonist JNJ 28610244 prevented fMLP‐induced, Mac‐1‐dependent adhesion, indicating that the H4receptor may block signals emanating from Mac‐1‐controlling degranulation. Likewise, engagement of the H4receptor by the selective agonist JNJ 28610244 blocked Mac‐1‐dependent activation of p38 MAPK, the kinase that controls neutrophil degranulation. We also show expression of the H4receptor at the mRNA level in ultrapure human neutrophils and myeloid leukemia PLB‐985 cells. We concluded that engagement of this receptor by selective H4receptor agonists may represent a good, therapeutic approach to accelerate resolution of inflammation. more...
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- 2014
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27. Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study
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De Groot, Pieter F., Belzer, Clara, Aydin, Ömrüm, Levin, Evgeni, Levels, Johannes H., Aalvink, Steven, Boot, Fransje, Holleman, Frits, Van Raalte, Daniël H., Scheithauer, Torsten P., Simsek, Suat, Schaap, Frank G., Olde Damink, Steven W M., Roep, Bart O., Hoekstra, Joost B., De Vos, Willem M., and Nieuwdorp, Max more...
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3. Good health - Abstract
PLoS one 12(12), e0188475 (2017). doi:10.1371/journal.pone.0188475, Published by PLoS, Lawrence, Kan.
28. Intestinal acetate and butyrate availability is associated with glucose metabolism in healthy individuals.
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Wijdeveld M, Schrantee A, Hagemeijer A, Nederveen AJ, Scheithauer TPM, Levels JHM, Prodan A, de Vos WM, Nieuwdorp M, and Ijzerman RG
- Abstract
Animal studies suggest that short-chain fatty acids acetate and butyrate are key players in the gut-brain axis and may affect insulin sensitivity. We investigated the association of intestinal acetate and butyrate availability (measured by butyryl-coenzyme A transferase (ButCoA) gene amount) with insulin sensitivity and secretion in healthy subjects from the HELIUS cohort study from the highest 15% (N = 30) and the lowest 15% (N = 30) intestinal ButCoA gene amount. The groups did not differ in insulin sensitivity or secretion. However, the high ButCoA group showed lower glucose and insulin peaks during the first 60 min after a meal and a higher nadir during the second 60 min (p < 0.01), suggesting delayed glucose adsorption from the small intestine. Our data suggest that chronically increased acetate and butyrate availability may improve glucose metabolism by delaying gastric emptying and intestinal adsorption. Future studies should further investigate the effect of acetate and butyrate interventions., Competing Interests: M.N. and W.M.d.V. are founders and scientific advisory board members of Caelus Health, the Netherlands., (© 2023 The Author(s).) more...
- Published
- 2023
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