109 results on '"Tremaroli, V."'
Search Results
2. Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects
- Author
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Bouter, K EC, Bakker, G J, Levin, E., Hartstra, A V, Kootte, R S, Udayappan, S D, Katiraei, S., Bahler, L., Gilijamse, P. W., Tremaroli, V., Stahlman, M., Holleman, F., van Riel, N. A. W., Verberne, H J, Romijn, J A, Dallinga-Thie, G M, Serlie, M J, Ackermans, M T, Kemper, E M, van Dijk, Willems K., Backhed, F., Groen, A K, and Nieuwdorp, M.
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- 2018
- Full Text
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3. Combinatorial, additive and dose-dependent drug-microbiome associations
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Forslund, SK, Chakaroun, R, Zimmermann-Kogadeeva, M, Markó, L, Aron-Wisnewsky, J, Nielsen, T, Moitinho-Silva, L, Schmidt, TSB, Falony, G, Vieira-Silva, S, Adriouch, S, Alves, RJ, Assmann, K, Bastard, J-P, Birkner, T, Caesar, R, Chilloux, J, Coelho, LP, Fezeu, L, Galleron, N, Helft, G, Isnard, R, Ji, B, Kuhn, M, Le Chatelier, E, Myridakis, A, Olsson, L, Pons, N, Prifti, E, Quinquis, B, Roume, H, Salem, J-E, Sokolovska, N, Tremaroli, V, Valles-Colomer, M, Lewinter, C, Søndertoft, NB, Pedersen, HK, Hansen, TH, Amouyal, C, Andersson Galijatovic, EA, Andreelli, F, Barthelemy, O, Batisse, J-P, Belda, E, Berland, M, Bittar, R, Blottière, H, Bosquet, F, Boubrit, R, Bourron, O, Camus, M, Cassuto, D, Ciangura, C, Collet, J-P, Dao, M-C, Djebbar, M, Doré, A, Engelbrechtsen, L, Fellahi, S, Fromentin, S, Galan, P, Gauguier, D, Giral, P, Hartemann, A, Hartmann, B, Holst, JJ, Hornbak, M, Hoyles, L, Hulot, J-S, Jaqueminet, S, Jørgensen, NR, Julienne, H, Justesen, J, Kammer, J, Krarup, N, Kerneis, M, Khemis, J, Kozlowski, R, Lejard, V, Levenez, F, Lucas-Martini, L, Massey, R, Martinez-Gili, L, Maziers, N, Medina-Stamminger, J, Montalescot, G, Moute, S, Neves, AL, Olanipekun, M, Le Pavin, LP, Poitou, C, Pousset, F, Pouzoulet, L, Rodriguez-Martinez, A, Rouault, C, Silvain, J, Svendstrup, M, Swartz, T, Vanduyvenboden, T, Vatier, C, Walther, S, Gøtze, JP, Køber, L, Vestergaard, H, Hansen, T, Zucker, J-D, Hercberg, S, Oppert, J-M, Letunic, I, Nielsen, J, Bäckhed, F, Ehrlich, SD, Dumas, M-E, Raes, J, Pedersen, O, Clément, K, Stumvoll, M, Bork, P, The MetaCardis Consortium (Hoyles, L.), European Molecular Biology Laboratory [Heidelberg] (EMBL), Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Berlin Institute of Health (BIH), German Center for Cardiovascular Research (DZHK), Universität Leipzig, Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Copenhagen = Københavns Universitet (UCPH), University of New South Wales [Sydney] (UNSW), Paul Scherrer Institute (PSI), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Heidelberg University, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Henri Mondor [Créteil], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], University of Gothenburg (GU), Imperial College London, MetaGenoPolis (MGP (US 1367)), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris-Saclay, Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chalmers University of Technology [Gothenburg, Sweden], Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)-Sorbonne Université (SU)-Institut de Recherche pour le Développement (IRD [France-Nord]), Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière] (CIC Paris-Est), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Biobyte Solutions [Heidelberg, Germany] (BS), IT University of Copenhagen (ITU), Sahlgrenska University Hospital [Gothenburg], Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, McGill University and Genome Quebec Innovation Centre, Helmholtz Institute Ulm (HIU), Helmholtz Zentrum München = German Research Center for Environmental Health, University of Würzburg = Universität Würzburg, Yonsei University, MetaCardis Consortium*: Chloe Amouyal, Ehm Astrid Andersson Galijatovic, Fabrizio Andreelli, Olivier Barthelemy, Jean-Paul Batisse, Eugeni Belda, Magalie Berland, Randa Bittar, Hervé Blottière, Frederic Bosquet, Rachid Boubrit, Olivier Bourron, Mickael Camus, Dominique Cassuto, Cecile Ciangura, Jean-Philippe Collet, Maria-Carlota Dao, Morad Djebbar, Angélique Doré, Line Engelbrechtsen, Soraya Fellahi, Sebastien Fromentin, Pilar Galan, Dominique Gauguier, Philippe Giral, Agnes Hartemann, Bolette Hartmann, Jens Juul Holst, Malene Hornbak, Lesley Hoyles, Jean-Sebastien Hulot, Sophie Jaqueminet, Niklas Rye Jørgensen, Hanna Julienne, Johanne Justesen, Judith Kammer, Nikolaj Krarup, Mathieu Kerneis, Jean Khemis, Ruby Kozlowski, Véronique Lejard, Florence Levenez, Lea Lucas-Martini, Robin Massey, Laura Martinez-Gili, Nicolas Maziers, Jonathan Medina-Stamminger, Gilles Montalescot, Sandrine Moute, Ana Luisa Neves, Michael Olanipekun, Laetitia Pasero Le Pavin, Christine Poitou, Francoise Pousset, Laurence Pouzoulet, Andrea Rodriguez-Martinez, Christine Rouault, Johanne Silvain, Mathilde Svendstrup, Timothy Swartz, Thierry Vanduyvenboden, Camille Vatier, Stefanie Walther., ANR-16-IDEX-0004,ULNE,ULNE(2016), ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018), Dumas, Marc-Emmanuel, Universität Leipzig [Leipzig], Service de Nutrition [CHU Pitié-Salpétrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Henri Mondor, Centre d'investigation clinique pluridisciplinaire [CHU Pitié Salpêtrière] (CIC-1901(ex CIC-1421)), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Imperial College London - National Heart and Lung Institute, and Division of Computational and Systems Medicine, Imperial College London, London, SW7 2AZ, UK
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Clostridiales ,Science & Technology ,Multidisciplinary ,ANTIBIOTIC USE ,IMPACT ,Microbiota ,[SDV]Life Sciences [q-bio] ,HUMAN GUT MICROBIOME ,Atherosclerosis ,Gastrointestinal Microbiome ,[SDV] Life Sciences [q-bio] ,Multidisciplinary Sciences ,PROTON PUMP INHIBITORS ,Cardiovascular and Metabolic Diseases ,GUIDELINE ,Metabolome ,MANAGEMENT ,Humans ,Science & Technology - Other Topics ,ALTERS - Abstract
During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1-5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease. ispartof: NATURE vol:600 issue:7889 pages:500-+ ispartof: location:England status: published
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- 2021
4. A systems biology approach to understand gut microbiota and host metabolism in morbid obesity:design of the BARIA Longitudinal Cohort Study
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Van Olden, C. C., Van de Laar, A. W., Meijnikman, A. S., Aydin, O., Van Olst, N., Hoozemans, J. B., De Brauw, L. M., Bruin, S. C., Acherman, Y. I. Z., Verheij, J., Pyykko, J. E., Hagedoorn, M., Sanderman, R., Bosma, N. C., Tremaroli, V., Lundqvist, A., Olofsson, L. E., Herrema, H., Lappa, D., Hjorth, S., Nielsen, J., Schwartz, T., Groen, A. K., Nieuwdorp, M., Backhed, F., Gerdes, V. E. A., Van Olden, C. C., Van de Laar, A. W., Meijnikman, A. S., Aydin, O., Van Olst, N., Hoozemans, J. B., De Brauw, L. M., Bruin, S. C., Acherman, Y. I. Z., Verheij, J., Pyykko, J. E., Hagedoorn, M., Sanderman, R., Bosma, N. C., Tremaroli, V., Lundqvist, A., Olofsson, L. E., Herrema, H., Lappa, D., Hjorth, S., Nielsen, J., Schwartz, T., Groen, A. K., Nieuwdorp, M., Backhed, F., and Gerdes, V. E. A.
- Abstract
Introduction Prevalence of obesity and associated diseases, including type 2 diabetes mellitus, dyslipidaemia and non-alcoholic fatty liver disease (NAFLD), are increasing. Underlying mechanisms, especially in humans, are unclear. Bariatric surgery provides the unique opportunity to obtain biopsies and portal vein blood-samples. Methods The BARIA Study aims to assess how microbiota and their metabolites affect transcription in key tissues and clinical outcome in obese subjects and how baseline anthropometric and metabolic characteristics determine weight loss and glucose homeostasis after bariatric surgery. We phenotype patients undergoing bariatric surgery (predominantly laparoscopic Roux-en-Y gastric bypass), before weight loss, with biometrics, dietary and psychological questionnaires, mixed meal test (MMT) and collect fecal-samples and intra-operative biopsies from liver, adipose tissues and jejunum. We aim to include 1500 patients. A subset (approximately 25%) will undergo intra-operative portal vein blood-sampling. Fecal-samples are analyzed with shotgun metagenomics and targeted metabolomics, fasted and postprandial plasma-samples are subjected to metabolomics, and RNA is extracted from the tissues for RNAseq-analyses. Data will be integrated using state-of-the-art neuronal networks and metabolic modeling. Patient follow-up will be ten years. Results Preoperative MMT of 170 patients were analysed and clear differences were observed in glucose homeostasis between individuals. Repeated MMT in 10 patients showed satisfactory intra-individual reproducibility, with differences in plasma glucose, insulin and triglycerides within 20% of the mean difference. Conclusion The BARIA study can add more understanding in how gut-microbiota affect metabolism, especially with regard to obesity, glucose metabolism and NAFLD. Identification of key factors may provide diagnostic and therapeutic leads to control the obesity-associated disease epidemic.
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- 2021
5. SY39-1INCREASED INTESTINAL PERMEABILITY IS RELATED TO GUT BACTERIAL DYSBIOSIS AND BEHAVIORAL MARKERS OF ADDICTION SEVERITY IN ALCOHOL-DEPENDENT SUBJECTS
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Leclercq, S., Matamoros, S., Cani, P. D., Francois, J., Starkel, P., Windey, K., Tremaroli, V., Backhed, F., Verbeke, K., de Timary, P., and Delzenne, N. M.
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- 2014
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6. Statin therapy is associated with lower prevalence of gut microbiota dysbiosis [plus Methods, Extended data figures, Supplementary information, and Nature Research reporting summary]
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Vieira-Silva, S., Falony, G., Belda, E., Nielsen, T., Aron-Wisnewsky, J., Chakaroun, R., Forslund, S.F., Assmann, K., Valles-Colomer, M., Nguyen, T.T.D., Proost, S., Prifti, E., Tremaroli, V., Pons, N., Le Chatelier, E., Andreelli, F., Bastard, J.P., Coelho, L.P., Galleron, N., Hulot, J.S., Lewinter, C., Pedersen, H.K., Quinquis, B., Rouault, C., Roume, H., Salem, J.E., Søndertoft, N.B., Touch, S., Dumas, M.E., Ehrlich, S.D., Galan, P., Gøtze, J.P., Hansen, T.H., Holst, J.S., Køber, L., Letunic, I., Nielsen, J., Oppert, J.M., Stumvoll, M., Vestergaard, H., Zucker, Jean-Daniel, Bork, P., Pedersen, O., Bäckhed, F., Clément, K., Raes, J., Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université (SU), Service de nutrition [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Sorbonne Université (SU)-Universtié Yaoundé 1 [Cameroun]-Université Cadi Ayyad [Marrakech] (UCA)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de la francophonie pour l'informatique-Institut de Recherche pour le Développement (IRD [France-Nord]), Service de diabétologie [CHU Pitié-Salpétrière], Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Service de pharmacologie biologique [CHU Pitié-Salpêtrière], CIC Paris Est, Sorbonne Université - Faculté de Médecine (SU FM), and Sorbonne Université (SU)
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[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease. Reported changes in stool consistency and inflammation status during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics.
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- 2020
7. The effect of saccharin consumption on microbiota composition and insulin sensitivity : a clinical, experimental open label pilot study
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Kalin, Kenny, Radholm, K., Wennberg, Maria, Tremaroli, V., Brolin, H., Woodward, M., Bäckhed, F., Rolandsson, Olov, Kalin, Kenny, Radholm, K., Wennberg, Maria, Tremaroli, V., Brolin, H., Woodward, M., Bäckhed, F., and Rolandsson, Olov
- Abstract
Background and aims: In a previous study it was suggested that consumption of saccharin, a non-caloric artificial sweetener (NAS), often consumed by individuals with type 2 diabetes mellitus, increases the risk of developing glucose intolerance in rodents and humans through microbiota alterations. However, the study was small and did not use insulin clamp, the gold standard for measuring insulin sensitivity in humans. Thus, our aim was to further investigate whether NAS affect insulin sensitivity and gut microbiota in humans. Materials and methods: We recruited 14 participants (8 women and 6 men) who were non-diabetic, 60.0 (IQR 56.8-64.0) years of age with a body mass index of 27.9 (IQR 27.1-28.5). The study was an open label study where participants acted as their own control. Their insulin sensitivity was measured before and after exposure of 240 mg saccharin/day for three months. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp and the ‘M value’ was calculated by dividing the glucose infusion rate during the last 60 minutes of the clamp by body weight (mg/kg/min). Stool samples were collected before and after saccharin consumption. Microbiota was analyzed by sequencing of the 16S rRNA gene. Results: Thirteen of the 14 participants completed the study. There was no change in insulin resistance after exposure to saccharin (mean M value difference (ΔM) 0.0 (SD 1.6). ΔM was not related to age or sex . Individual M values from the first and second insulin clamp are shown in Figure 1 and indicate some individual responses. During the study 6 participants reduced their HbA1c ≥ 3 mmol/mol. Overall, there was no change in composition or richness of the gut microbiota as a result of saccharin consumption. Furthermore, there was no change in microbiota at end of follow-up for participants with a HbA1c reduction compared to participants without a HbA1c reduction of 3 mmol/mol or more. However, there were small differences in gut microbiota between HbA1c
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- 2020
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8. Distinct differences in gut microbial composition and functional potential from lean to morbidly obese subjects
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Meijnikman, A. S., Aydin, O., Prodan, A., Tremaroli, V., Herrema, H., Levin, E., Acherman, Y., Bruin, S., Gerdes, V. E., Backhed, F., Groen, A. K., Nieuwdorp, M., Meijnikman, A. S., Aydin, O., Prodan, A., Tremaroli, V., Herrema, H., Levin, E., Acherman, Y., Bruin, S., Gerdes, V. E., Backhed, F., Groen, A. K., and Nieuwdorp, M.
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- 2020
9. A systems biology approach to understand gut microbiota and host metabolism in morbid obesity: design of the BARIA Longitudinal Cohort Study
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Van Olden, C. C., primary, Van de Laar, A. W., additional, Meijnikman, A. S., additional, Aydin, O., additional, Van Olst, N., additional, Hoozemans, J. B., additional, De Brauw, L. M., additional, Bruin, S. C., additional, Acherman, Y. I. Z., additional, Verheij, J., additional, Pyykkö, J. E., additional, Hagedoorn, M., additional, Sanderman, R., additional, Bosma, N. C., additional, Tremaroli, V., additional, Lundqvist, A., additional, Olofsson, L. E., additional, Herrema, H., additional, Lappa, D., additional, Hjorth, S., additional, Nielsen, J., additional, Schwartz, T., additional, Groen, A. K., additional, Nieuwdorp, M., additional, Bäckhed, F., additional, and Gerdes, V. E. A., additional
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- 2020
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10. Mikrobielle Regulation von Hexokinase 2 koordiniert mitochondrialen Metabolismus und Zelltod bei akuter Colitis
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Hamm, J, additional, Hinrichsen, F, additional, Mishra, N, additional, Shima, K, additional, Sommer, N, additional, Klischies, K, additional, Prasse, D, additional, Tremaroli, V, additional, Basic, M, additional, Häsler, R, additional, Schröder, L, additional, Schmitz-Streit, R, additional, Stecher, B, additional, Rupp, J, additional, Bäckhed, F, additional, Rosenstiel, P, additional, and Sommer, F, additional
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- 2020
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11. Distinct differences in gut microbial composition and functional potential from lean to morbidly obese subjects
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Meijnikman, A. S., primary, Aydin, O., additional, Prodan, A., additional, Tremaroli, V., additional, Herrema, H., additional, Levin, E., additional, Acherman, Y., additional, Bruin, S., additional, Gerdes, V.E., additional, Backhed, F., additional, Groen, A.K., additional, and Nieuwdorp, M., additional
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- 2020
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12. VEgetaRian Diet in patients with Ischemic heart disease (VERDI) : an open-label, randomized, prospective, cross-over study
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Djekic, Demir, Carlsson, F., Landberg, R., Särnqvist, C., Cao, Yang, Tremaroli, V., Backhed, F., Fröbert, Ole, Djekic, Demir, Carlsson, F., Landberg, R., Särnqvist, C., Cao, Yang, Tremaroli, V., Backhed, F., and Fröbert, Ole
- Abstract
Background: A vegetarian diet (VD) in patients diagnosed with ischemic heart disease (IHD) may reduce future cardiovascular risk. Purpose: The study hypothesis was that patients diagnosed with IHD can benefit from a VD assessed by multiple risk markers for this type of disease. Methods: In a crossover study patients diagnosed with IHD, treated by percutaneous coronary intervention and on optimal medical therapy were randomly allocated to a 4-week intervention with ready-made (lunch and dinner) isocaloric VD or meat diet (MD). The primary outcome was change in oxidized low-density lipoprotein cholesterol (LDL-C) levels. Secondary outcomes were difference in changes of blood lipids, weight, body mass index (BMI), blood pressure, heart rate, glycated haemoglobin (HbA1c), number of participants reaching guideline target values, quality of life, gut microbiota, and trimethylamine N-oxide between the two interventions. Results: 31 participants were recruited (median age: 67 years, male sex: 93.5%). Significant between-intervention differences (VD vs MD) were found in oxidized LDL-C (-2.73 U/L; p=.015), total cholesterol (TC) (-0.13 mmol/L, p=.01), LDL-C (-0.10 mmol/L; p=.02), weight (-0.67 kg, p=.008) and BMI (-0.21 kg/m2, p=.009). After VD, numerically more subjects reached guideline LDL-C target values (87% vs 77%) but this did not reach statistical significance (p=.07). During VD intervention the diet led to a significant reduction in oxidized LDL-C, TC, LDL-C, HDL-C, ApoB, and ApoB/ApoA1 ratio. Conclusions: Our results suggest that in patients with IHD a VD compared to a MD, lowers oxidative stress, improves lipid profile and lowers BMI.
- Published
- 2019
13. P6208VEgetaRian Diet in patients with Ischemic heart disease (VERDI): an open-label, randomized, prospective, cross-over study
- Author
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Djekic, D, primary, Carlsson, F, additional, Landberg, R, additional, Sarnqvist, C, additional, Cao, Y, additional, Tremaroli, V, additional, Backhed, F, additional, and Frobert, O, additional
- Published
- 2019
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14. A systems biology approach to understand gut microbiota and host metabolism in morbid obesity: design of the BARIA Longitudinal Cohort Study.
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Van Olden, C. C., Van de Laar, A. W., Meijnikman, A. S., Aydin, O., Van Olst, N., Hoozemans, J. B., De Brauw, L. M., Bruin, S. C., Acherman, Y. I. Z., Verheij, J., Pyykkö, J. E., Hagedoorn, M., Sanderman, R., Bosma, N. C., Tremaroli, V., Lundqvist, A., Olofsson, L. E., Herrema, H., Lappa, D., and Hjorth, S.
- Subjects
GASTRIC bypass ,MORBID obesity ,SYSTEMS biology ,GUT microbiome ,FATTY liver ,TYPE 2 diabetes - Abstract
Introduction: Prevalence of obesity and associated diseases, including type 2 diabetes mellitus, dyslipidaemia and non‐alcoholic fatty liver disease (NAFLD), are increasing. Underlying mechanisms, especially in humans, are unclear. Bariatric surgery provides the unique opportunity to obtain biopsies and portal vein blood‐samples. Methods: The BARIA Study aims to assess how microbiota and their metabolites affect transcription in key tissues and clinical outcome in obese subjects and how baseline anthropometric and metabolic characteristics determine weight loss and glucose homeostasis after bariatric surgery. We phenotype patients undergoing bariatric surgery (predominantly laparoscopic Roux‐en‐Y gastric bypass), before weight loss, with biometrics, dietary and psychological questionnaires, mixed meal test (MMT) and collect fecal‐samples and intra‐operative biopsies from liver, adipose tissues and jejunum. We aim to include 1500 patients. A subset (approximately 25%) will undergo intra‐operative portal vein blood‐sampling. Fecal‐samples are analyzed with shotgun metagenomics and targeted metabolomics, fasted and postprandial plasma‐samples are subjected to metabolomics, and RNA is extracted from the tissues for RNAseq‐analyses. Data will be integrated using state‐of‐the‐art neuronal networks and metabolic modeling. Patient follow‐up will be ten years. Results: Preoperative MMT of 170 patients were analysed and clear differences were observed in glucose homeostasis between individuals. Repeated MMT in 10 patients showed satisfactory intra‐individual reproducibility, with differences in plasma glucose, insulin and triglycerides within 20% of the mean difference. Conclusion: The BARIA study can add more understanding in how gut‐microbiota affect metabolism, especially with regard to obesity, glucose metabolism and NAFLD. Identification of key factors may provide diagnostic and therapeutic leads to control the obesity‐associated disease epidemic. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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15. Differential metabolic effects of oral butyrate treatment in lean versus metabolic syndrome subjects
- Author
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Bouter, Kec, Bakker, G.J., Levin, E., Hartstra, A.V., Kootte, R.S., Udayappan, S.D., Katiraei, S., Bahler, L., Gilijamse, P.W., Tremaroli, V., Stahlman, M., Holleman, F., van Riel, N.A.W., Verberne, H.J., Romijn, J.A., Dallinga-Thie, G.M., Serlie, M.J., Ackermans, M.T., Kemper, E.M., Willems van Dijk, K., Backhed, F., Groen, A.K., Nieuwdorp, M., Bouter, Kec, Bakker, G.J., Levin, E., Hartstra, A.V., Kootte, R.S., Udayappan, S.D., Katiraei, S., Bahler, L., Gilijamse, P.W., Tremaroli, V., Stahlman, M., Holleman, F., van Riel, N.A.W., Verberne, H.J., Romijn, J.A., Dallinga-Thie, G.M., Serlie, M.J., Ackermans, M.T., Kemper, E.M., Willems van Dijk, K., Backhed, F., Groen, A.K., and Nieuwdorp, M.
- Abstract
Background: Gut microbiota-derived short-chain fatty acids (SCFAs) have been associated with beneficial metabolic effects. However, the direct effect of oral butyrate on metabolic parameters in humans has never been studied. In this first in men pilot study, we thus treated both lean and metabolic syndrome male subjects with oral sodium butyrate and investigated the effect on metabolism. Methods: Healthy lean males (n = 9) and metabolic syndrome males (n = 10) were treated with oral 4 g of sodium butyrate daily for 4 weeks. Before and after treatment, insulin sensitivity was determined by a two-step hyperinsulinemic euglycemic clamp using [6,6- 2 H 2 ]-glucose. Brown adipose tissue (BAT) uptake of glucose was visualized using 18 F-FDG PET-CT. Fecal SCFA and bile acid concentrations as well as microbiota composition were determined before and after treatment. Results: Oral butyrate had no effect on plasma and fecal butyrate levels after treatment, but did alter other SCFAs in both plasma and feces. Moreover, only in healthy lean subjects a significant improvement was observed in both peripheral (median Rd: from 71 to 82 μmol/kg min, p < 0.05) and hepatic insulin sensitivity (EGP suppression from 75 to 82% p < 0.05). Although BAT activity was significantly higher at baseline in lean (SUVmax: 12.4 ± 1.8) compared with metabolic syndrome subjects (SUVmax: 0.3 ± 0.8, p < 0.01), no significant effect following butyrate treatment on BAT was observed in either group (SUVmax lean to 13.3 ± 2.4 versus metabolic syndrome subjects to 1.2 ± 4.1). Conclusions: Oral butyrate treatment beneficially affects glucose metabolism in lean but not metabolic syndrome subjects, presumably due to an altered SCFA handling in insulin-resistant subjects. Although preliminary, these first in men findings argue against oral butyrate supplementation as treatment for glucose regulation in human subjects with type 2 diabetes mellitus.
- Published
- 2018
16. Tellurite reduction by cells of Rhodobacter capsulatus: transport, cell viability and oxidative stress
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Borsetti F., Michelacci F., Tremaroli V. ., ZANNONI, DAVIDE, BORGHESE, ROBERTO, Borsetti F., Michelacci F., Tremaroli V., Borghese R., and Zannoni D.
- Published
- 2004
17. SY19-2GUT BACTERIAL DYSBIOSIS IS RELATED TO THE SEVERITY OF ALCOHOL-DEPENDENCE
- Author
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Leclercq, S., primary, Matamoros, S., additional, Cani, P. D., additional, Stärkel, P., additional, Bäckhed, F., additional, Tremaroli, V., additional, Windey, K., additional, Verbeke, K., additional, Delzenne, N. M., additional, and de Timary, P., additional
- Published
- 2015
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18. INCREASED INTESTINAL PERMEABILITY IS RELATED TO GUT BACTERIAL DYSBIOSIS AND BEHAVIORAL MARKERS OF ADDICTION SEVERITY IN ALCOHOL-DEPENDENT SUBJECTS
- Author
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Leclercq, Sophie, primary, Matamoros, S., additional, Cani, P. D., additional, Francois, J., additional, Starkel, P., additional, Windey, K., additional, Tremaroli, V., additional, Backhed, F., additional, Verbeke, K., additional, de Timary, P., additional, and Delzenne, N. M., additional
- Published
- 2015
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19. SY39-1 * INCREASED INTESTINAL PERMEABILITY IS RELATED TO GUT BACTERIAL DYSBIOSIS AND BEHAVIORAL MARKERS OF ADDICTION SEVERITY IN ALCOHOL-DEPENDENT SUBJECTS
- Author
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Leclercq, S., primary, Matamoros, S., additional, Cani, P. D., additional, Francois, J., additional, Starkel, P., additional, Windey, K., additional, Tremaroli, V., additional, Backhed, F., additional, Verbeke, K., additional, de Timary, P., additional, and Delzenne, N. M., additional
- Published
- 2014
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20. The gut microbiota regulates bone mass in mice
- Author
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Sjogren⁎, K., primary, Engdahl, C., additional, Henning, P., additional, Lerner, U.H., additional, Tremaroli, V., additional, Lagerquist, M.K., additional, Bäckhed, F., additional, and Ohlsson, C., additional
- Published
- 2012
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21. A histidine-kinasecheAgene ofPseudomonas pseudoalcaligensKF707 not only has a key role in chemotaxis but also affects biofilm formation and cell metabolism
- Author
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Tremaroli, V., primary, Fedi, S., additional, Tamburini, S., additional, Viti, C., additional, Tatti, E., additional, Ceri, H., additional, Turner, R. J., additional, and Zannoni, D., additional
- Published
- 2010
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22. A histidine-kinase cheA gene of Pseudomonas pseudoalcaligens KF707 not only has a key role in chemotaxis but also affects biofilm formation and cell metabolism.
- Author
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Tremaroli, V., Fedi, S., Tamburini, S., Viti, C., Tatti, E., Ceri, H., Turner, R. J., and Zannoni, D.
- Subjects
HISTIDINE kinases ,CELL metabolism ,BIOFILMS ,CHEMOTAXIS ,PSEUDOMONAS metabolism ,GENES ,PHENOTYPES - Abstract
A histidine-kinase cheA gene in Pseudomonas pseudoalcaligenes KF707 plays a central role in the regulation of metabolic responses as well as in chemotaxis. Non-chemotactic mutants harboring insertions into the cheA gene were screened for their ability to form biofilms in the Calgary biofilm device. Notably, ≥95% decrease in the number of cells attached to the polystyrene surface was observed in cheA mutants compared to the KF707 wild-type biofilm phenotype. The ability to form mature biofilms was restored to wild-type levels, providing functional copies of the KF707 cheA gene to the mutants. In addition, phenotype micro-arrays and proteomic analyses revealed that several basic metabolic activities and a few periplasmic binding proteins of cheA mutant cells differed compared to those of wild-type cells. These results are interpreted as evidence of a strong integration between chemotactic and metabolic pathways in the process of biofilm development by P. pseudoalcaligenes KF707. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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- View/download PDF
23. Evidence for a tellurite-dependent generation of reactive oxygen species and absence of a tellurite-mediated adaptive response to oxidative stress in cells of Pseudomonas pseudoalcaligenes KF707
- Author
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Stefano Fedi, Valentina Tremaroli, Davide Zannoni, Tremaroli V, Fedi S, and Zannoni D.
- Subjects
Pseudomonas pseudoalcaligenes ,medicine.disease_cause ,Biochemistry ,Microbiology ,Superoxide dismutase ,chemistry.chemical_compound ,Tellurite ,Paraquat ,Genetics ,medicine ,Hydrogen peroxide ,Molecular Biology ,chemistry.chemical_classification ,Reactive oxygen species ,biology ,Superoxide ,General Medicine ,Obligate aerobe ,biology.organism_classification ,Adaptation, Physiological ,Oxidative Stress ,chemistry ,Pseudomonas pseudoalcaligenes KF707 ,biology.protein ,Oxidative stre ,Tellurium ,Reactive Oxygen Species ,Oxidative stress - Abstract
Tellurite (TeO3(2-)) is the most toxic and soluble oxyanion among tellurium (Te) compounds. The effects of the metalloid anion on the oxidative stress response of the obligate aerobe Pseudomonas pseudoalcaligenes KF707 were investigated. Cells treated with sub-lethal concentrations of TeO3(2-) showed neither adaptation to it nor cross-protection against oxidants such as 1,1'-4,4'-bipyridinium dichloride (paraquat, PQ2+), diazenedicarboxylic acid bis-N,N-dimethylamide (diamide), tert-butyl hydroperoxide (tBH) and hydrogen peroxide (H2O2). Notably, TeO3(2-) exerted a synergic effect on the toxicity of these latter oxidants. Tellurite was shown to decrease the cellular content of reduced thiols (RSH) with a consequent increase in the production of reactive oxygen species (ROS) and stimulation of the superoxide dismutase (SOD) activity. However, since the time course of ROS production by TeO3(2) (t1/2 > 30 min) was much slower than that with PQ2+ and/or diamide (t1/2
- Published
- 2006
24. A histidine-kinase cheA gene of Pseudomonas pseudoalcaligenes KF707 not only has a key role in chemotaxis but also affects biofilm formation and cell metabolism
- Author
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Stefano Fedi, Sabrina Tamburini, Enrico Tatti, Davide Zannoni, Carlo Viti, Valentina Tremaroli, Raymond J. Turner, Howard Ceri, Tremaroli V., Fedi S., Tamburini S., Viti C., Ceri H., Turner R.J., and Zannoni D.
- Subjects
BIOFILMS ,Molecular Sequence Data ,Pseudomonas pseudoalcaligenes ,Mutant ,Phenotype micro-arrays ,Proteomic analysis ,Methyl-Accepting Chemotaxis Proteins ,Aquatic Science ,Settore BIO/19 - Microbiologia Generale ,Applied Microbiology and Biotechnology ,Bacterial Proteins ,Tandem Mass Spectrometry ,Electrophoresis, Gel, Two-Dimensional ,Amino Acid Sequence ,Phylogeny ,Water Science and Technology ,P. PSEUDOALCALIGENES KF707 ,Microscopy, Confocal ,biology ,Biofilm ,cheA gene ,Chemotaxis ,Pseudomonas pseudoalcaligenes KF707 ,Methyl-accepting chemotaxis protein ,CHEA GENE ,Histidine kinase ,Pseudomonas ,Membrane Proteins ,biology.organism_classification ,CHEMOTAXIS ,HISTIDINE KINASE ,Biochemistry ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Mutation ,Periplasmic Binding Proteins ,bacteria ,biological phenomena, cell phenomena, and immunity ,Protein Kinases ,Signal Transduction - Abstract
A histidine-kinase cheA gene in Pseudomonas pseudoalcaligenes KF707 plays a central role in the regulation of metabolic responses as well as in chemotaxis. Non-chemotactic mutants harboring insertions into the cheA gene were screened for their ability to form biofilms in the Calgary biofilm device. Notably, ≥95% decrease in the number of cells attached to the polystyrene surface was observed in cheA mutants compared to the KF707 wild-type biofilm phenotype. The ability to form mature biofilms was restored to wild-type levels, providing functional copies of the KF707 cheA gene to the mutants. In addition, phenotype micro-arrays and proteomic analyses revealed that several basic metabolic activities and a few periplasmic binding proteins of cheA mutant cells differed compared to those of wild-type cells. These results are interpreted as evidence of a strong integration between chemotactic and metabolic pathways in the process of biofilm development by P. pseudoalcaligenes KF707.
- Published
- 2011
25. Pseudomonas pseudoalcaligenes KF707 upon biofilm formation on a polystyrene surface acquire a strong antibiotic resistance with minor changes in their tolerance to metal cations and metalloid oxyanions
- Author
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Stefano Fedi, Valentina Tremaroli, Raymond J. Turner, Howard Ceri, Davide Zannoni, Tremaroli V, Fedi S, Turner RJ, Ceri H, and Zannoni D.
- Subjects
Anions ,Multidrug tolerance ,Pseudomonas pseudoalcaligenes ,Microbial Sensitivity Tests ,Biochemistry ,Microbiology ,METAL AND METALLOID TOLERANCE ,Cations ,Drug Resistance, Bacterial ,Genetics ,Molecular Biology ,Amikacin ,Soil Microbiology ,Microscopy, Confocal ,biology ,Chemistry ,fungi ,BIOFILM FORMATION ,Biofilm ,General Medicine ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,Obligate aerobe ,POLYSTYRENE SURFACE ,Anti-Bacterial Agents ,Culture Media ,PSEUDOMONAS PSEUDOALCALIGENES KF707 ,Metals ,Biofilms ,Pseudomonadales ,Polystyrenes ,CALGARY DEVICE BIOFILM ,Metalloid ,Rifampin ,Bacteria ,Pseudomonadaceae - Abstract
The susceptibility to various biocides was examined in planktonic cells and biofilms of the obligate aerobe, PCBs degrader, Pseudomonas pseudoalcaligenes KF707. The toxicity of two antibiotics, amikacin and rifampicin, three metalloid oxyanions (AsO2 −, SeO3 2−, TeO3 2−) and three metal cations (Cd2+, Ni2+, Al3+) was tested at two stages of the biofilm-development (4 and 24 h) and compared to planktonic cells susceptibility. Mature biofilms formed in rich (LB, Luria–Bertani) medium were thicker (23 μm) than biofilms grown in minimal (SA saccarose-arginine) medium (13 μm). Early grown (4 h) SA-biofilms, which consisted of a few sparse/attached cells, were 50–100 times more resistant to antibiotics than planktonic cells. Conversely, minor changes in tolerance to metal(loid)s were seen in both SA- and LB-grown biofilms. In contrast to planktonic cells, no reduction of TeO3 2− to elemental Te(0) or SeO3 2− to elemental Se(0) was seen in KF707 biofilms. The data indicate that: (a) metal tolerance in KF707 biofilms, under the growth and exposure conditions described here, is different than antibiotic tolerance; (b) KF707 planktonic cells and biofilms, are almost equally susceptible to killing by metal cations and oxyanions, and (c) biofilm-tolerance to TeO3 2− and SeO3 2− is not linked to metalloid reduction; this means that KF707 planktonic cells and biofilms differ in their physiology and strategy to counteract metalloid toxicity.
- Published
- 2007
26. Tellurite effects on Rhodobacter capsulatus cell viability and superoxide dismutase (SOD) activity under oxidative stress conditions
- Author
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BORSETTI, FRANCESCA, TREMAROLI, VALENTINA, BORGHESE, ROBERTO, ZANNONI, DAVIDE, Michelacci F., Winterstein C., Daldal F., Borsetti F., Tremaroli V., Michelacci F., Borghese R., Winterstein C., Daldal F., and Zannoni D.
- Published
- 2005
27. T-RFLP analysis of bacterial communities in cyclodextrin-amended bioreactors developed for biodegradation of polychlorinated biphenyls
- Author
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David J. Scala, Valentina Tremaroli, Lily Y. Young, Fabio Fava, Davide Zannoni, José R. Pérez-Jiménez, Stefano Fedi, S. Fedi, Tremaroli V., Scala D., Perez-Jimenez J., Fava F., Young L., and Zannoni D.
- Subjects
Soil test ,Biology ,complex mixtures ,Microbiology ,DNA, Ribosomal ,Bioremediation ,Bioreactors ,RNA, Ribosomal, 16S ,Proteobacteria ,Bioreactor ,Soil Pollutants ,Molecular Biology ,Ecosystem ,Phylogeny ,chemistry.chemical_classification ,Cyclodextrin ,Ecology ,beta-Cyclodextrins ,General Medicine ,Sequence Analysis, DNA ,Biodegradation ,16S ribosomal RNA ,biology.organism_classification ,Polychlorinated Biphenyls ,Biodegradation, Environmental ,chemistry ,Environmental chemistry ,Restriction fragment length polymorphism ,Polymorphism, Restriction Fragment Length - Abstract
In this study, T-RFLP analysis was used to determine the structure and spatial distribution of the indigenous bacterial community of an actual-site PCB-contaminated soil treated in aerobic packed-bed loop reactors (PBLRs) in the absence or in the presence of a mixture of randomly methylated beta-cyclodextrins (RAMEB) at 0.5 or 1% w/w. RAMEB was found to significantly enhance the aerobic bioremediation of soil with effects that increased proportionally with the concentration at which it was applied. At the end of treatment (180 days), T-RFLP analysis of the soil samples collected from the top and bottom regions of the PBLRs showed a series of 50 single T-RFs. Remarkably, the number of T-RFs was significantly lower (13-22) in samples collected from different sections of the RAMEB-amended bioreactors with respect to equivalent samples collected from the RAMEB-free reactor. Cluster analysis based on the presence or the absence of T-RFs peaks revealed high similarity, inside each reactor, between the top and bottom parts of its soil bed. Soil samples collected at the top and bottom regions of the two bioreactors amended with RAMEB, clustered together while the equivalent samples of the bioreactor without RAMEB formed a separate cluster which was distantly related to the soil samples obtained from the parallel amended bioreactor. Notably, T-RFLP analyses combined with extensive sequencing of 16S rDNA allowed us to tentatively allocate a series of bacterial species corresponding to specific peaks of the T-RFLP profiles and to determine their phylogenetic affiliation.
- Published
- 2004
28. The gut microbiota regulates bone mass in mice
- Author
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⁎, K., Engdahl, C., Henning, P., Lerner, U.H., Tremaroli, V., Lagerquist, M.K., Bäckhed, F., and Ohlsson, C.
- Published
- 2012
- Full Text
- View/download PDF
29. The Gut Microbiota and Diabetes: Research, Translation, and Clinical Applications-2023 Diabetes, Diabetes Care, and Diabetologia Expert Forum.
- Author
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Byndloss M, Devkota S, Duca F, Hendrik Niess J, Nieuwdorp M, Orho-Melander M, Sanz Y, Tremaroli V, and Zhao L
- Subjects
- Humans, Diabetes Mellitus microbiology, Gastrointestinal Microbiome physiology, Diabetes Mellitus, Type 2 microbiology
- Abstract
This article summarizes the state of the science on the role of the gut microbiota (GM) in diabetes from a recent international expert forum organized by Diabetes, Diabetes Care, and Diabetologia, which was held at the European Association for the Study of Diabetes 2023 Annual Meeting in Hamburg, Germany. Forum participants included clinicians and basic scientists who are leading investigators in the field of the intestinal microbiome and metabolism. Their conclusions were as follows: 1) the GM may be involved in the pathophysiology of type 2 diabetes, as microbially produced metabolites associate both positively and negatively with the disease, and mechanistic links of GM functions (e.g., genes for butyrate production) with glucose metabolism have recently emerged through the use of Mendelian randomization in humans; 2) the highly individualized nature of the GM poses a major research obstacle, and large cohorts and a deep-sequencing metagenomic approach are required for robust assessments of associations and causation; 3) because single-time point sampling misses intraindividual GM dynamics, future studies with repeated measures within individuals are needed; and 4) much future research will be required to determine the applicability of this expanding knowledge to diabetes diagnosis and treatment, and novel technologies and improved computational tools will be important to achieve this goal., (© 2024 by the American Diabetes Association and the European Association for the Study of Diabetes.)
- Published
- 2024
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- View/download PDF
30. Tissue-resident bacteria in metabolic diseases: emerging evidence and challenges.
- Author
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Massier L, Musat N, Stumvoll M, Tremaroli V, Chakaroun R, and Kovacs P
- Subjects
- Humans, Animals, Inflammation microbiology, Microbiota, Metabolic Diseases microbiology, Metabolic Diseases metabolism, Gastrointestinal Microbiome, Bacteria metabolism
- Abstract
Although the impact of the gut microbiome on health and disease is well established, there is controversy regarding the presence of microorganisms such as bacteria and their products in organs and tissues. However, recent contamination-aware findings of tissue-resident microbial signatures provide accumulating evidence in support of bacterial translocation in cardiometabolic disease. The latter provides a distinct paradigm for the link between microbial colonizers of mucosal surfaces and host metabolism. In this Perspective, we re-evaluate the concept of tissue-resident bacteria including their role in metabolic low-grade tissue and systemic inflammation. We examine the limitations and challenges associated with studying low bacterial biomass samples and propose experimental and analytical strategies to overcome these issues. Our Perspective aims to encourage further investigation of the mechanisms linking tissue-resident bacteria to host metabolism and their potentially actionable health implications for prevention and treatment., (© 2024. Springer Nature Limited.)
- Published
- 2024
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31. ForePass endoscopic bypass device for obesity and insulin resistance-metabolic treatment in a swine model.
- Author
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Angelini G, Galvao Neto M, Boskoski I, Caristo ME, Russo S, Proto L, Previti E, Olsson L, Aggarwal H, Pezzica S, Ferrari E, Bove V, Genco A, Bornstein S, Tremaroli V, Gastaldelli A, and Mingrone G
- Subjects
- Swine, Animals, Obesity surgery, Endoscopes, Insulin Resistance, Bariatric Surgery, Gastric Bypass, Obesity, Morbid surgery
- Abstract
Competing Interests: Competing interests: GA reports consulting fees from Metadeq and GHP Scientific. IB reports consulting fees from Apollo, Endosurgery, AndoTools, Nitinotes, Erbe Elektromedizin, Boston Scientific, Cook Medical and Pentax Medical. MGN reports consulting fees from Apollo EndoSurgery, USGI and Keyron. He is also a Scientific Advisor of Keyron and Morphic Medical. VB reports consulting fees from Apollo EndoSurgery. GM reports consulting fees from Novo Nordisk, Fractyl, Recor. She is also Scientific Advisor of Keyron, Metadeq, GHP Scientific, and Jemyll. All other authors declare no competing interests.
- Published
- 2024
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32. The interplay between dietary fatty acids and gut microbiota influences host metabolism and hepatic steatosis.
- Author
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Schoeler M, Ellero-Simatos S, Birkner T, Mayneris-Perxachs J, Olsson L, Brolin H, Loeber U, Kraft JD, Polizzi A, Martí-Navas M, Puig J, Moschetta A, Montagner A, Gourdy P, Heymes C, Guillou H, Tremaroli V, Fernández-Real JM, Forslund SK, Burcelin R, and Caesar R
- Subjects
- Humans, Male, Animals, Mice, Fatty Acids, Bile Acids and Salts, Dietary Fats, Gastrointestinal Microbiome, Microbiota, Fatty Liver
- Abstract
Dietary lipids can affect metabolic health through gut microbiota-mediated mechanisms, but the influence of lipid-microbiota interaction on liver steatosis is largely unknown. We investigate the impact of dietary lipids on human gut microbiota composition and the effects of microbiota-lipid interactions on steatosis in male mice. In humans, low intake of saturated fatty acids (SFA) is associated with increased microbial diversity independent of fiber intake. In mice, poorly absorbed dietary long-chain SFA, particularly stearic acid, induce a shift in bile acid profile and improved metabolism and steatosis. These benefits are dependent on the gut microbiota, as they are transmitted by microbial transfer. Diets enriched in polyunsaturated fatty acids are protective against steatosis but have minor influence on the microbiota. In summary, we find that diets enriched in poorly absorbed long-chain SFA modulate gut microbiota profiles independent of fiber intake, and this interaction is relevant to improve metabolism and decrease liver steatosis., (© 2023. Springer Nature Limited.)
- Published
- 2023
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33. Synergy and oxygen adaptation for development of next-generation probiotics.
- Author
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Khan MT, Dwibedi C, Sundh D, Pradhan M, Kraft JD, Caesar R, Tremaroli V, Lorentzon M, and Bäckhed F
- Subjects
- Animals, Humans, Mice, Butyrates metabolism, Oxygen metabolism, Oxygen pharmacology, Aerobiosis, Faecalibacterium prausnitzii drug effects, Faecalibacterium prausnitzii metabolism, Symbiosis, Gastrointestinal Microbiome, Probiotics metabolism, Biotechnology methods
- Abstract
The human gut microbiota has gained interest as an environmental factor that may contribute to health or disease
1 . The development of next-generation probiotics is a promising strategy to modulate the gut microbiota and improve human health; however, several key candidate next-generation probiotics are strictly anaerobic2 and may require synergy with other bacteria for optimal growth. Faecalibacterium prausnitzii is a highly prevalent and abundant human gut bacterium associated with human health, but it has not yet been developed into probiotic formulations2 . Here we describe the co-isolation of F. prausnitzii and Desulfovibrio piger, a sulfate-reducing bacterium, and their cross-feeding for growth and butyrate production. To produce a next-generation probiotic formulation, we adapted F. prausnitzii to tolerate oxygen exposure, and, in proof-of-concept studies, we demonstrate that the symbiotic product is tolerated by mice and humans (ClinicalTrials.gov identifier: NCT03728868 ) and is detected in the human gut in a subset of study participants. Our study describes a technology for the production of next-generation probiotics based on the adaptation of strictly anaerobic bacteria to tolerate oxygen exposures without a reduction in potential beneficial properties. Our technology may be used for the development of other strictly anaerobic strains as next-generation probiotics., (© 2023. The Author(s).)- Published
- 2023
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34. Protein supplementation changes gut microbial diversity and derived metabolites in subjects with type 2 diabetes.
- Author
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Attaye I, Lassen PB, Adriouch S, Steinbach E, Patiño-Navarrete R, Davids M, Alili R, Jacques F, Benzeguir S, Belda E, Nemet I, Anderson JT, Alexandre-Heymann L, Greyling A, Larger E, Hazen SL, van Oppenraaij SL, Tremaroli V, Beck K, Bergh PO, Bäckhed F, Ten Brincke SPM, Herrema H, Groen AK, Pinto-Sietsma SJ, Clément K, and Nieuwdorp M
- Abstract
High-protein diets are promoted for individuals with type 2 diabetes (T2D). However, effects of dietary protein interventions on (gut-derived) metabolites in T2D remains understudied. We therefore performed a multi-center, randomized-controlled, isocaloric protein intervention with 151 participants following either 12-week high-protein (HP; 30Energy %, N = 78) vs. low-protein (LP; 10 Energy%, N = 73) diet. Primary objectives were dietary effects on glycemic control which were determined via glycemic excursions, continuous glucose monitors and HbA1c. Secondary objectives were impact of diet on gut microbiota composition and -derived metabolites which were determined by shotgun-metagenomics and mass spectrometry. Analyses were performed using delta changes adjusting for center, baseline, and kidney function when appropriate. This study found that a short-term 12-week isocaloric protein modulation does not affect glycemic parameters or weight in metformin-treated T2D. However, the HP diet slightly worsened kidney function, increased alpha-diversity, and production of potentially harmful microbiota-dependent metabolites, which may affect host metabolism upon prolonged exposure., Competing Interests: M.N. is in the SAB of Caelus health; however, this is not relevant for the current paper. S.L.H. reports being named as co-inventor on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics, being a paid consultant formerly for Procter & Gamble in the past, and currently with Zehna Therapeutics, and both receiving research funds from Procter & Gamble, Zehna Therapeutics, and Roche Diagnostics, and being eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Procter & Gamble, Zehna Therapeutics, and Cleveland HeartLab, a wholly owned subsidiary of Quest Diagnostics., (© 2023 The Author(s).)
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- 2023
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35. Self-organized metabotyping of obese individuals identifies clusters responding differently to bariatric surgery.
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Lappa D, Meijnikman AS, Krautkramer KA, Olsson LM, Aydin Ö, Van Rijswijk AS, Acherman YIZ, De Brauw ML, Tremaroli V, Olofsson LE, Lundqvist A, Hjorth SA, Ji B, Gerdes VEA, Groen AK, Schwartz TW, Nieuwdorp M, Bäckhed F, and Nielsen J
- Subjects
- Humans, Obesity surgery, Adipose Tissue, Algorithms, Diabetes Mellitus, Type 2 surgery, Bariatric Surgery
- Abstract
Weight loss through bariatric surgery is efficient for treatment or prevention of obesity related diseases such as type 2 diabetes and cardiovascular disease. Long term weight loss response does, however, vary among patients undergoing surgery. Thus, it is difficult to identify predictive markers while most obese individuals have one or more comorbidities. To overcome such challenges, an in-depth multiple omics analyses including fasting peripheral plasma metabolome, fecal metagenome as well as liver, jejunum, and adipose tissue transcriptome were performed for 106 individuals undergoing bariatric surgery. Machine leaning was applied to explore the metabolic differences in individuals and evaluate if metabolism-based patients' stratification is related to their weight loss responses to bariatric surgery. Using Self-Organizing Maps (SOMs) to analyze the plasma metabolome, we identified five distinct metabotypes, which were differentially enriched for KEGG pathways related to immune functions, fatty acid metabolism, protein-signaling, and obesity pathogenesis. The gut metagenome of the most heavily medicated metabotypes, treated simultaneously for multiple cardiometabolic comorbidities, was significantly enriched in Prevotella and Lactobacillus species. This unbiased stratification into SOM-defined metabotypes identified signatures for each metabolic phenotype and we found that the different metabotypes respond differently to bariatric surgery in terms of weight loss after 12 months. An integrative framework that utilizes SOMs and omics integration was developed for stratifying a heterogeneous bariatric surgery cohort. The multiple omics datasets described in this study reveal that the metabotypes are characterized by a concrete metabolic status and different responses in weight loss and adipose tissue reduction over time. Our study thus opens a path to enable patient stratification and hereby allow for improved clinical treatments., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Lappa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2023
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36. 6α-hydroxylated bile acids mediate TGR5 signalling to improve glucose metabolism upon dietary fiber supplementation in mice.
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Makki K, Brolin H, Petersen N, Henricsson M, Christensen DP, Khan MT, Wahlström A, Bergh PO, Tremaroli V, Schoonjans K, Marschall HU, and Bäckhed F
- Subjects
- Animals, Mice, Body Weight, Mice, Inbred C57BL, Mice, Knockout, Bile Acids and Salts metabolism, Dietary Supplements, Glucose metabolism, Receptors, G-Protein-Coupled genetics, Receptors, G-Protein-Coupled metabolism, Dietary Fiber administration & dosage, Gastrointestinal Microbiome, Diet, Western
- Abstract
Objective: Dietary fibres are essential for maintaining microbial diversity and the gut microbiota can modulate host physiology by metabolising the fibres. Here, we investigated whether the soluble dietary fibre oligofructose improves host metabolism by modulating bacterial transformation of secondary bile acids in mice fed western-style diet., Design: To assess the impact of dietary fibre supplementation on bile acid transformation by gut bacteria, we fed conventional wild-type and TGR5 knockout mice western-style diet enriched or not with cellulose or oligofructose. In addition, we used germ-free mice and in vitro cultures to evaluate the activity of bacteria to transform bile acids in the caecal content of mice fed with western-style diet enriched with oligofructose. Finally, we treated wild-type and TGR5 knockout mice orally with hyodeoxycholic acid to assess its antidiabetic effects., Results: We show that oligofructose sustains the production of 6α-hydroxylated bile acids from primary bile acids by gut bacteria when fed western-style diet. Mechanistically, we demonstrated that the effects of oligofructose on 6α-hydroxylated bile acids were microbiota dependent and specifically required functional TGR5 signalling to reduce body weight gain and improve glucose metabolism. Furthermore, we show that the 6α-hydroxylated bile acid hyodeoxycholic acid stimulates TGR5 signalling, in vitro and in vivo, and increases GLP-1R activity to improve host glucose metabolism., Conclusion: Modulation of the gut microbiota with oligofructose enriches bacteria involved in 6α-hydroxylated bile acid production and leads to TGR5-GLP1R axis activation to improve body weight and metabolism under western-style diet feeding in mice., Competing Interests: Competing interests: FB receives research funding from Biogaia AB and is founder and shareholder of Implexion AB, which are unrelated to this study., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)
- Published
- 2023
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37. Upper gut heat shock proteins HSP70 and GRP78 promote insulin resistance, hyperglycemia, and non-alcoholic steatohepatitis.
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Angelini G, Castagneto-Gissey L, Salinari S, Bertuzzi A, Anello D, Pradhan M, Zschätzsch M, Ritter P, Le Roux CW, Rubino F, Basso N, Casella G, Bornstein SR, Tremaroli V, and Mingrone G
- Subjects
- Rats, Animals, Endoplasmic Reticulum Chaperone BiP, Heat-Shock Proteins metabolism, Insulin metabolism, Diet, High-Fat adverse effects, HSP70 Heat-Shock Proteins metabolism, Liver metabolism, Glucose metabolism, Insulin Resistance genetics, Non-alcoholic Fatty Liver Disease metabolism, Hyperglycemia metabolism, Hepatitis
- Abstract
A high-fat diet increases the risk of insulin resistance, type-2 diabetes, and non-alcoholic steato-hepatitis. Here we identified two heat-shock proteins, Heat-Shock-Protein70 and Glucose-Regulated Protein78, which are increased in the jejunum of rats on a high-fat diet. We demonstrated a causal link between these proteins and hepatic and whole-body insulin-resistance, as well as the metabolic response to bariatric/metabolic surgery. Long-term continuous infusion of Heat-Shock-Protein70 and Glucose-Regulated Protein78 caused insulin-resistance, hyperglycemia, and non-alcoholic steato-hepatitis in rats on a chow diet, while in rats on a high-fat diet continuous infusion of monoclonal antibodies reversed these phenotypes, mimicking metabolic surgery. Infusion of these proteins or their antibodies was also associated with shifts in fecal microbiota composition. Serum levels of Heat-Shock-Protein70 and Glucose-Regulated Protein78were elevated in patients with non-alcoholic steato-hepatitis, but decreased following metabolic surgery. Understanding the intestinal regulation of metabolism may provide options to reverse metabolic diseases., (© 2022. The Author(s).)
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- 2022
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38. Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism.
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Belda E, Voland L, Tremaroli V, Falony G, Adriouch S, Assmann KE, Prifti E, Aron-Wisnewsky J, Debédat J, Le Roy T, Nielsen T, Amouyal C, André S, Andreelli F, Blüher M, Chakaroun R, Chilloux J, Coelho LP, Dao MC, Das P, Fellahi S, Forslund S, Galleron N, Hansen TH, Holmes B, Ji B, Krogh Pedersen H, Le P, Le Chatelier E, Lewinter C, Mannerås-Holm L, Marquet F, Myridakis A, Pelloux V, Pons N, Quinquis B, Rouault C, Roume H, Salem JE, Sokolovska N, Søndertoft NB, Touch S, Vieira-Silva S, Galan P, Holst J, Gøtze JP, Køber L, Vestergaard H, Hansen T, Hercberg S, Oppert JM, Nielsen J, Letunic I, Dumas ME, Stumvoll M, Pedersen OB, Bork P, Ehrlich SD, Zucker JD, Bäckhed F, Raes J, and Clément K
- Subjects
- Humans, Mice, Animals, Prebiotics, Biotin pharmacology, Mice, Inbred C57BL, Obesity metabolism, Inflammation, Gastrointestinal Microbiome, Obesity, Morbid surgery, Diabetes Mellitus, Type 2, Vitamin B Complex pharmacology
- Abstract
Objectives: Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome's functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation., Design: We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice., Results: Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration., Conclusion: Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity., Trial Registration Number: NCT02059538., Competing Interests: Competing interests: KC is a consultant for Danone Research, Ysopia and CONFO therapeutics for work not associated with this study. KC held a collaborative research contract with Danone Research in the context of MetaCardis project. FB is a shareholder of Implexion pharma AB. MB received lecture and/or consultancy fees from AstraZeneca, Boehringer-Ingelheim, Lilly, Novo Nordisk, Novartis and Sanofi., (© 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.)
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- 2022
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39. Microbiome-derived ethanol in nonalcoholic fatty liver disease.
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Meijnikman AS, Davids M, Herrema H, Aydin O, Tremaroli V, Rios-Morales M, Levels H, Bruin S, de Brauw M, Verheij J, Kemper M, Holleboom AG, Tushuizen ME, Schwartz TW, Nielsen J, Brandjes D, Dirinck E, Weyler J, Verrijken A, De Block CEM, Vonghia L, Francque S, Beuers U, Gerdes VEA, Bäckhed F, Groen AK, and Nieuwdorp M
- Subjects
- Alcohol Dehydrogenase, Anti-Bacterial Agents, Ethanol, Humans, Liver pathology, Prospective Studies, Microbiota, Non-alcoholic Fatty Liver Disease pathology
- Abstract
To test the hypothesis that the gut microbiota of individuals with nonalcoholic fatty liver disease (NAFLD) produce enough ethanol to be a driving force in the development and progression of this complex disease, we performed one prospective clinical study and one intervention study. Ethanol was measured while fasting and 120 min after a mixed meal test (MMT) in 146 individuals. In a subset of 37 individuals and in an external validation cohort, ethanol was measured in portal vein blood. In an intervention study, ten individuals with NAFLD and ten overweight but otherwise healthy controls were infused with a selective alcohol dehydrogenase (ADH) inhibitor before an MMT. When compared to fasted peripheral blood, median portal vein ethanol concentrations were 187 (interquartile range (IQR), 17-516) times higher and increased with disease progression from 2.1 mM in individuals without steatosis to 8.0 mM in NAFL 21.0 mM in nonalcoholic steatohepatitis. Inhibition of ADH induced a 15-fold (IQR,1.6- to 20-fold) increase in peripheral blood ethanol concentrations in individuals with NAFLD, although this effect was abolished after antibiotic treatment. Specifically, Lactobacillaceae correlated with postprandial peripheral ethanol concentrations (Spearman's rho, 0.42; P < 10
-5 ) in the prospective study. Our data show that the first-pass effect obscures the levels of endogenous ethanol production, suggesting that microbial ethanol could be considered in the pathogenesis of this highly prevalent liver disease., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)- Published
- 2022
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40. Hyperinsulinemia Is Highly Associated With Markers of Hepatocytic Senescence in Two Independent Cohorts.
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Meijnikman AS, van Olden CC, Aydin Ö, Herrema H, Kaminska D, Lappa D, Männistö V, Tremaroli V, Olofsson LE, de Brauw M, van de Laar A, Verheij J, Gerdes VEA, Schwartz TW, Nielsen J, Bäckhed F, Pajukanta P, Pihlajamäki J, Tchkonia T, Kirkland JL, Kuipers F, Nieuwdorp M, and Groen AK
- Subjects
- Biomarkers, Humans, Insulin, Liver, Diabetes Mellitus, Type 2 complications, Hyperinsulinism complications, Insulin Resistance, Non-alcoholic Fatty Liver Disease complications
- Abstract
Cellular senescence is an essentially irreversible growth arrest that occurs in response to various cellular stressors and may contribute to development of type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD). In this article, we investigated whether chronically elevated insulin levels are associated with cellular senescence in the human liver. In 107 individuals undergoing bariatric surgery, hepatic senescence markers were assessed by immunohistochemistry as well as transcriptomics. A subset of 180 participants from the ongoing Finnish Kuopio OBesity Surgery (KOBS) study was used as validation cohort. We found plasma insulin to be highly associated with various markers of cellular senescence in liver tissue. The liver transcriptome of individuals with high insulin revealed significant upregulation of several genes associated with senescence: p21, TGFβ, PI3K, HLA-G, IL8, p38, Ras, and E2F. Insulin associated with hepatic senescence independently of NAFLD and plasma glucose. By using transcriptomic data from the KOBS study, we could validate the association of insulin with p21 in the liver. Our results support a potential role for hyperinsulinemia in induction of cellular senescence in the liver. These findings suggest possible benefits of lowering insulin levels in obese individuals with insulin resistance., (© 2022 by the American Diabetes Association.)
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- 2022
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41. A systems biology approach to study non-alcoholic fatty liver (NAFL) in women with obesity.
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Meijnikman AS, Lappa D, Herrema H, Aydin O, Krautkramer KA, Tremaroli V, Olofsson LE, Lundqvist A, Bruin S, Acherman Y, Verheij J, Hjorth S, Gerdes VEA, Schwartz TW, Groen AK, Bäckhed F, Nielsen J, and Nieuwdorp M
- Abstract
Non-alcoholic fatty liver disease (NAFLD) is now the most frequent global chronic liver disease. Individuals with NAFLD exhibited an increased risk of all-cause mortality driven by extrahepatic cancers and liver and cardiovascular disease. Once the disease is established, women have a higher risk of disease progression and worse outcome. It is therefore critical to deepen the current knowledge on the pathophysiology of NAFLD in women. Here, we used a systems biology approach to investigate the contribution of different organs to this disease. We analyzed transcriptomics profiles of liver and adipose tissues, fecal metagenomes, and plasma metabolomes of 55 women with and without NAFLD. We observed differences in metabolites, expression of human genes, and gut microbial features between the groups and revealed that there is substantial crosstalk between these different omics sets. Multi-omics analysis of individuals with NAFLD may provide novel strategies to study the pathophysiology of NAFLD in humans., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)
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- 2022
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42. Gut microbial characteristics in poor appetite and undernutrition: a cohort of older adults and microbiota transfer in germ-free mice.
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Fluitman KS, Davids M, Olofsson LE, Wijdeveld M, Tremaroli V, Keijser BJF, Visser M, Bäckhed F, Nieuwdorp M, and IJzerman RG
- Subjects
- Animals, Appetite, Body Weight, Cohort Studies, Cross-Sectional Studies, Humans, Male, Mice, RNA, Ribosomal, 16S genetics, Weight Loss, Gastrointestinal Microbiome, Malnutrition, Microbiota
- Abstract
Background: Older adults are particularly prone to the development of poor appetite and undernutrition. Possibly, this is partly due to the aged gut microbiota. We aimed to evaluate the gut microbiota in relation to both poor appetite and undernutrition in community-dwelling older adults. Furthermore, we studied the causal effects of the microbiota on body weight and body composition by transferring faecal microbiota from cohort participants into germ-free mice., Methods: First, we conducted a cross-sectional cohort study of 358 well-phenotyped Dutch community-dwelling older adults from the Longitudinal Aging Study Amsterdam. Data collection included body measurements, a faecal and blood sample, as well as extensive questionnaires on appetite, dietary intake, and nutritional status. Appetite was assessed by the Council of Nutrition Appetite Questionnaire (CNAQ) and undernutrition was defined by either a low body mass index (BMI) (BMI < 20 kg/m
2 if <70 years or BMI < 22 kg/m2 if ≥70 years) or >5% body weight loss averaged over the last 2 years. Gut microbiota composition was determined with 16S rRNA sequencing. Next, we transferred faecal microbiota from 12 cohort participants with and without low BMI or recent weight loss into a total of 41 germ-free mice to study the potential causal effects of the gut microbiota on host BMI and body composition., Results: The mean age (range) of our cohort was 73 (65-93); 58.4% was male. Seventy-seven participants were undernourished and 21 participants had poor appetite (CNAQ < 28). A lower abundance of the genus Blautia was associated with undernutrition (log2 fold change = -0.57, Benjamini-Hochberg-adjusted P = 0.008), whereas higher abundances of taxa from Lachnospiraceae, Ruminococcaceae UCG-002, Parabacteroides merdae, and Dorea formicigenerans were associated with poor appetite. Furthermore, participants with poor appetite or undernutrition had reduced levels of faecal acetate (P = 0.006 and 0.026, respectively). Finally, there was a trend for the mice that received faecal microbiota from older adults with low BMI to weigh 1.26 g less after 3 weeks (P = 0.086) and have 6.13% more lean mass (in % body weight, P = 0.067) than the mice that received faecal microbiota from older adults without low BMI or recent weight loss., Conclusions: This study demonstrates several associations of the gut microbiota with both poor appetite and undernutrition in older adults. Moreover, it is the first to explore a causal relation between the aged gut microbiota and body weight and body composition in the host. Possibly, microbiota-manipulating strategies will benefit older adults prone to undernutrition., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)- Published
- 2022
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43. Dynamics of the normal gut microbiota: A longitudinal one-year population study in Sweden.
- Author
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Olsson LM, Boulund F, Nilsson S, Khan MT, Gummesson A, Fagerberg L, Engstrand L, Perkins R, Uhlén M, Bergström G, Tremaroli V, and Bäckhed F
- Subjects
- Bacteria genetics, Bifidobacterium genetics, Feces microbiology, RNA, Ribosomal, 16S genetics, Sweden, Gastrointestinal Microbiome genetics
- Abstract
Temporal dynamics of the gut microbiota potentially limit the identification of microbial features associated with health status. Here, we used whole-genome metagenomic and 16S rRNA gene sequencing to characterize the intra- and inter-individual variations of gut microbiota composition and functional potential of a disease-free Swedish population (n = 75) over one year. We found that 23% of the total compositional variance was explained by intra-individual variation. The degree of intra-individual compositional variability was negatively associated with the abundance of Faecalibacterium prausnitzii (a butyrate producer) and two Bifidobacterium species. By contrast, the abundance of facultative anaerobes and aerotolerant bacteria such as Escherichia coli and Lactobacillus acidophilus varied extensively, independent of compositional stability. The contribution of intra-individual variance to the total variance was greater for functional pathways than for microbial species. Thus, reliable quantification of microbial features requires repeated samples to address the issue of intra-individual variations of the gut microbiota., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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44. Propionate attenuates atherosclerosis by immune-dependent regulation of intestinal cholesterol metabolism.
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Haghikia A, Zimmermann F, Schumann P, Jasina A, Roessler J, Schmidt D, Heinze P, Kaisler J, Nageswaran V, Aigner A, Ceglarek U, Cineus R, Hegazy AN, van der Vorst EPC, Döring Y, Strauch CM, Nemet I, Tremaroli V, Dwibedi C, Kränkel N, Leistner DM, Heimesaat MM, Bereswill S, Rauch G, Seeland U, Soehnlein O, Müller DN, Gold R, Bäckhed F, Hazen SL, Haghikia A, and Landmesser U
- Subjects
- Animals, Apolipoproteins E metabolism, Cholesterol metabolism, Cholesterol, LDL metabolism, Humans, Intestinal Absorption, Mice, Mice, Inbred C57BL, Mice, Knockout, Atherosclerosis etiology, Propionates pharmacology, Propionates therapeutic use
- Abstract
Aims: Atherosclerotic cardiovascular disease (ACVD) is a major cause of mortality and morbidity worldwide, and increased low-density lipoproteins (LDLs) play a critical role in development and progression of atherosclerosis. Here, we examined for the first time gut immunomodulatory effects of the microbiota-derived metabolite propionic acid (PA) on intestinal cholesterol metabolism., Methods and Results: Using both human and animal model studies, we demonstrate that treatment with PA reduces blood total and LDL cholesterol levels. In apolipoprotein E-/- (Apoe-/-) mice fed a high-fat diet (HFD), PA reduced intestinal cholesterol absorption and aortic atherosclerotic lesion area. Further, PA increased regulatory T-cell numbers and interleukin (IL)-10 levels in the intestinal microenvironment, which in turn suppressed the expression of Niemann-Pick C1-like 1 (Npc1l1), a major intestinal cholesterol transporter. Blockade of IL-10 receptor signalling attenuated the PA-related reduction in total and LDL cholesterol and augmented atherosclerotic lesion severity in the HFD-fed Apoe-/- mice. To translate these preclinical findings to humans, we conducted a randomized, double-blinded, placebo-controlled human study (clinical trial no. NCT03590496). Oral supplementation with 500 mg of PA twice daily over the course of 8 weeks significantly reduced LDL [-15.9 mg/dL (-8.1%) vs. -1.6 mg/dL (-0.5%), P = 0.016], total [-19.6 mg/dL (-7.3%) vs. -5.3 mg/dL (-1.7%), P = 0.014] and non-high-density lipoprotein cholesterol levels [PA vs. placebo: -18.9 mg/dL (-9.1%) vs. -0.6 mg/dL (-0.5%), P = 0.002] in subjects with elevated baseline LDL cholesterol levels., Conclusion: Our findings reveal a novel immune-mediated pathway linking the gut microbiota-derived metabolite PA with intestinal Npc1l1 expression and cholesterol homeostasis. The results highlight the gut immune system as a potential therapeutic target to control dyslipidaemia that may introduce a new avenue for prevention of ACVDs., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2022
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45. Microbiome and metabolome features of the cardiometabolic disease spectrum.
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Fromentin S, Forslund SK, Chechi K, Aron-Wisnewsky J, Chakaroun R, Nielsen T, Tremaroli V, Ji B, Prifti E, Myridakis A, Chilloux J, Andrikopoulos P, Fan Y, Olanipekun MT, Alves R, Adiouch S, Bar N, Talmor-Barkan Y, Belda E, Caesar R, Coelho LP, Falony G, Fellahi S, Galan P, Galleron N, Helft G, Hoyles L, Isnard R, Le Chatelier E, Julienne H, Olsson L, Pedersen HK, Pons N, Quinquis B, Rouault C, Roume H, Salem JE, Schmidt TSB, Vieira-Silva S, Li P, Zimmermann-Kogadeeva M, Lewinter C, Søndertoft NB, Hansen TH, Gauguier D, Gøtze JP, Køber L, Kornowski R, Vestergaard H, Hansen T, Zucker JD, Hercberg S, Letunic I, Bäckhed F, Oppert JM, Nielsen J, Raes J, Bork P, Stumvoll M, Segal E, Clément K, Dumas ME, Ehrlich SD, and Pedersen O
- Subjects
- Humans, Longitudinal Studies, Metabolome, Middle Aged, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Microbiota
- Abstract
Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages-acute coronary syndrome, chronic IHD and IHD with heart failure-and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features., (© 2022. The Author(s).)
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- 2022
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46. Microbial regulation of hexokinase 2 links mitochondrial metabolism and cell death in colitis.
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Hinrichsen F, Hamm J, Westermann M, Schröder L, Shima K, Mishra N, Walker A, Sommer N, Klischies K, Prasse D, Zimmermann J, Kaiser S, Bordoni D, Fazio A, Marinos G, Laue G, Imm S, Tremaroli V, Basic M, Häsler R, Schmitz RA, Krautwald S, Wolf A, Stecher B, Schmitt-Kopplin P, Kaleta C, Rupp J, Bäckhed F, Rosenstiel P, and Sommer F
- Subjects
- Animals, Caco-2 Cells, Cell Death physiology, Epithelial Cells metabolism, Histone Deacetylases metabolism, Humans, Mice, Mitochondria metabolism, Repressor Proteins metabolism, Colitis metabolism, Colitis microbiology, Hexokinase metabolism
- Abstract
Hexokinases (HK) catalyze the first step of glycolysis limiting its pace. HK2 is highly expressed in gut epithelium, contributes to immune responses, and is upregulated during inflammation. We examined the microbial regulation of HK2 and its impact on inflammation using mice lacking HK2 in intestinal epithelial cells (Hk2
ΔIEC ). Hk2ΔIEC mice were less susceptible to acute colitis. Analyzing the epithelial transcriptome from Hk2ΔIEC mice during colitis and using HK2-deficient intestinal organoids and Caco-2 cells revealed reduced mitochondrial respiration and epithelial cell death in the absence of HK2. The microbiota strongly regulated HK2 expression and activity. The microbially derived short-chain fatty acid (SCFA) butyrate repressed HK2 expression via histone deacetylase 8 (HDAC8) and reduced mitochondrial respiration in wild-type but not in HK2-deficient Caco-2 cells. Butyrate supplementation protected wild-type but not Hk2ΔIEC mice from colitis. Our findings define a mechanism how butyrate promotes intestinal homeostasis and suggest targeted HK2-inhibition as therapeutic avenue for inflammation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)- Published
- 2021
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47. Combinatorial, additive and dose-dependent drug-microbiome associations.
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Forslund SK, Chakaroun R, Zimmermann-Kogadeeva M, Markó L, Aron-Wisnewsky J, Nielsen T, Moitinho-Silva L, Schmidt TSB, Falony G, Vieira-Silva S, Adriouch S, Alves RJ, Assmann K, Bastard JP, Birkner T, Caesar R, Chilloux J, Coelho LP, Fezeu L, Galleron N, Helft G, Isnard R, Ji B, Kuhn M, Le Chatelier E, Myridakis A, Olsson L, Pons N, Prifti E, Quinquis B, Roume H, Salem JE, Sokolovska N, Tremaroli V, Valles-Colomer M, Lewinter C, Søndertoft NB, Pedersen HK, Hansen TH, Gøtze JP, Køber L, Vestergaard H, Hansen T, Zucker JD, Hercberg S, Oppert JM, Letunic I, Nielsen J, Bäckhed F, Ehrlich SD, Dumas ME, Raes J, Pedersen O, Clément K, Stumvoll M, and Bork P
- Subjects
- Clostridiales, Humans, Metabolome, Atherosclerosis, Gastrointestinal Microbiome, Microbiota
- Abstract
During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery
1-5 . Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2021
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48. Therapeutic Potential of Butyrate for Treatment of Type 2 Diabetes.
- Author
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Arora T and Tremaroli V
- Subjects
- Animals, Bacteria metabolism, Feces microbiology, Gastrointestinal Microbiome drug effects, Humans, Butyrates pharmacology, Diabetes Mellitus, Type 2 drug therapy
- Abstract
Metagenomics studies have shown that type 2 diabetes (T2D) is associated with an altered gut microbiota. Whereas different microbiota patterns have been observed in independent human cohorts, reduction of butyrate-producing bacteria has consistently been found in individuals with T2D, as well as in those with prediabetes. Butyrate is produced in the large intestine by microbial fermentations, particularly of dietary fiber, and serves as primary fuel for colonocytes. It also acts as histone deacetylase inhibitor and ligand to G-protein coupled receptors, affecting cellular signaling in target cells, such as enteroendocrine cells. Therefore, butyrate has become an attractive drug target for T2D, and treatment strategies have been devised to increase its intestinal levels, for example by supplementation of butyrate-producing bacteria and dietary fiber, or through fecal microbiota transplant (FMT). In this review, we provide an overview of current literature indicating that these strategies have yielded encouraging results and short-term benefits in humans, but long-term improvements of glycemic control have not been reported so far. Further studies are required to find effective approaches to restore butyrate-producing bacteria and butyrate levels in the human gut, and to investigate their impact on glucose regulation in T2D., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Arora and Tremaroli.)
- Published
- 2021
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49. Anorexia and Fat Aversion Induced by Vertical Sleeve Gastrectomy Is Attenuated in Neurotensin Receptor 1-Deficient Mice.
- Author
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Ratner C, Shin JH, Dwibedi C, Tremaroli V, Bjerregaard A, Hartmann B, Bäckhed F, Leinninger G, Seeley RJ, and Holst B
- Subjects
- Animals, Anorexia genetics, Dietary Fats, Gastrectomy methods, Male, Mice, Mice, Knockout, Phobic Disorders etiology, Phobic Disorders genetics, Postoperative Complications psychology, Anorexia etiology, Avoidant Restrictive Food Intake Disorder, Gastrectomy adverse effects, Postoperative Complications genetics, Receptors, Neurotensin genetics
- Abstract
Neurotensin (NT) is an anorexic gut hormone and neuropeptide that increases in circulation following bariatric surgery in humans and rodents. We sought to determine the contribution of NT to the metabolic efficacy of vertical sleeve gastrectomy (VSG). To explore a potential mechanistic role of NT in VSG, we performed sham or VSG surgeries in diet-induced obese NT receptor 1 (NTSR1) wild-type and knockout (ko) mice and compared their weight and fat mass loss, glucose tolerance, food intake, and food preference after surgery. NTSR1 ko mice had reduced initial anorexia and body fat loss. Additionally, NTSR1 ko mice had an attenuated reduction in fat preference following VSG. Results from this study suggest that NTSR1 signaling contributes to the potent effect of VSG to initially reduce food intake following VSG surgeries and potentially also on the effects on macronutrient selection induced by VSG. However, maintenance of long-term weight loss after VSG requires signals in addition to NT., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2021
- Full Text
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50. Developmental trajectory of the healthy human gut microbiota during the first 5 years of life.
- Author
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Roswall J, Olsson LM, Kovatcheva-Datchary P, Nilsson S, Tremaroli V, Simon MC, Kiilerich P, Akrami R, Krämer M, Uhlén M, Gummesson A, Kristiansen K, Dahlgren J, and Bäckhed F
- Subjects
- Adult, Bacteria classification, Bacteria genetics, Child Development, Child, Preschool, Cohort Studies, Feces microbiology, Female, Humans, Infant, Male, Sweden, Young Adult, Bacteria growth & development, Bacteria isolation & purification, Gastrointestinal Microbiome
- Abstract
The gut is inhabited by a densely populated ecosystem, the gut microbiota, that is established at birth. However, the succession by which different bacteria are incorporated into the gut microbiota is still relatively unknown. Here, we analyze the microbiota from 471 Swedish children followed from birth to 5 years of age, collecting samples after 4 and 12 months and at 3 and 5 years of age as well as from their mothers at birth using 16S rRNA gene profiling. We also compare their microbiota to an adult Swedish population. Genera follow 4 different colonization patterns during establishment where Methanobrevibacter and Christensenellaceae colonize late and do not reached adult levels at 5 years. These late colonizers correlate with increased alpha diversity in both children and adults. By following the children through age-specific community types, we observe that children have individual dynamics in the gut microbiota development trajectory., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
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