Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism
Eugeni Belda
(1)
,
Lise Voland
(2)
,
Valentina Tremaroli
(3)
,
Gwen Falony
(4)
,
Solia Adriouch
(5, 2)
,
Karen Assmann
(5, 2)
,
Edi Prifti
(6)
,
Judith Aron-Wisnewsky
(7, 2)
,
Jean Debédat
(2)
,
Tiphaine Le Roy
(1, 2)
,
Trine Nielsen
(8)
,
Chloé Amouyal
(7)
,
Sébastien André
(2)
,
Fabrizio Andreelli
(2)
,
Matthias Blüher
(9)
,
Rima Chakaroun
,
Julien Chilloux
(10)
,
Luis Pedro Coelho
(11)
,
Maria Carlota Dao
(2)
,
Promi Das
(12)
,
Soraya Fellahi
(13, 14)
,
Sofia Forslund
(15)
,
Nathalie Galleron
(16)
,
Tue Hansen
(8)
,
Bridget Holmes
(17)
,
Boyang Ji
(12)
,
Helle Krogh Pedersen
(8)
,
Phuong Le
(2)
,
Emmanuelle Le Chatelier
(16)
,
Christian Lewinter
(18)
,
Louise Mannerås-Holm
(19)
,
Florian Marquet
(2)
,
Antonis Myridakis
(20)
,
Veronique Pelloux
(2)
,
Nicolas Pons
(16)
,
Benoit Quinquis
(16)
,
Christine Rouault
(2)
,
Hugo Roume
(16)
,
Joe-Elie Salem
(21)
,
Nataliya Sokolovska
(2)
,
Nadja Søndertoft
(8)
,
Sothea Touch
(2)
,
Sara Vieira-Silva
(22)
,
Pilar Galan
(23, 24)
,
Jens Holst
(8)
,
Jens Peter Gøtze
(18)
,
Lars Køber
(18)
,
Henrik Vestergaard
(8)
,
Torben Hansen
(8)
,
Serge Hercberg
(23, 24)
,
Jean-Michel Oppert
(7)
,
Jens Nielsen
(12)
,
Ivica Letunic
(25)
,
Marc-Emmanuel M.-E. Dumas
(20)
,
Michael Stumvoll
(26)
,
Oluf Borbye Pedersen
(8)
,
Peer Bork
(11)
,
Stanislav Dusko Ehrlich
(16)
,
Jean-Daniel Zucker
(6, 2)
,
Fredrik Bäckhed
(27)
,
Jeroen Raes
(22)
,
Karine Clément
(2)
1
ICAN -
Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
2 Nutriomics - Nutrition et obésités: approches systémiques (UMR-S 1269)
3 GU - Göteborgs Universitet = University of Gothenburg
4 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
5 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
6 UMMISCO - Unité de modélisation mathématique et informatique des systèmes complexes [Bondy]
7 CHU Pitié-Salpêtrière [AP-HP]
8 CBMR - Novo Nordisk Foundation Center for Basic Metabolic Research
9 Leipzig University / Universität Leipzig
10 Nutrition et cerveau (U1213, U855)
11 EMBL - European Molecular Biology Laboratory [Heidelberg]
12 Chalmers University of Technology [Göteborg]
13 CRSA - Centre de Recherche Saint-Antoine
14 CHU Tenon [AP-HP]
15 MDC - Max Delbrück Center for Molecular Medicine [Berlin]
16 MGP (US 1367) - MetaGenoPolis
17 Danone Nutricia Research [Utrecht]
18 Rigshospitalet [Copenhagen]
19 Sahlgrenska University Hospital [Gothenburg]
20 Imperial College London
21 CIC Paris-Est - Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière]
22 VIB - Vlaams Instituut voor Biotechnologie [Ghent, Belgique]
23 UREN - Unité de Recherche en Epidémiologie Nutritionnelle
24 EREN [CRESS - U1153 / UMR_A 1125] - Nutritional Epidemiology Research Team | Equipe de Recherche en Epidémiologie Nutritionnelle
25 Biobyte Solutions GMBH
26 HMGU - Helmholtz Zentrum München = German Research Center for Environmental Health
27 Sahlgrenska Academy at University of Gothenburg [Göteborg]
2 Nutriomics - Nutrition et obésités: approches systémiques (UMR-S 1269)
3 GU - Göteborgs Universitet = University of Gothenburg
4 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
5 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
6 UMMISCO - Unité de modélisation mathématique et informatique des systèmes complexes [Bondy]
7 CHU Pitié-Salpêtrière [AP-HP]
8 CBMR - Novo Nordisk Foundation Center for Basic Metabolic Research
9 Leipzig University / Universität Leipzig
10 Nutrition et cerveau (U1213, U855)
11 EMBL - European Molecular Biology Laboratory [Heidelberg]
12 Chalmers University of Technology [Göteborg]
13 CRSA - Centre de Recherche Saint-Antoine
14 CHU Tenon [AP-HP]
15 MDC - Max Delbrück Center for Molecular Medicine [Berlin]
16 MGP (US 1367) - MetaGenoPolis
17 Danone Nutricia Research [Utrecht]
18 Rigshospitalet [Copenhagen]
19 Sahlgrenska University Hospital [Gothenburg]
20 Imperial College London
21 CIC Paris-Est - Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière]
22 VIB - Vlaams Instituut voor Biotechnologie [Ghent, Belgique]
23 UREN - Unité de Recherche en Epidémiologie Nutritionnelle
24 EREN [CRESS - U1153 / UMR_A 1125] - Nutritional Epidemiology Research Team | Equipe de Recherche en Epidémiologie Nutritionnelle
25 Biobyte Solutions GMBH
26 HMGU - Helmholtz Zentrum München = German Research Center for Environmental Health
27 Sahlgrenska Academy at University of Gothenburg [Göteborg]
Gwen Falony
- Fonction : Auteur
- PersonId : 1194648
- ORCID : 0000-0003-2450-0782
Edi Prifti
- Fonction : Auteur
- PersonId : 1151183
- IdHAL : edi-prifti
- ORCID : 0000-0001-8861-1305
- IdRef : 155572822
Jean Debédat
- Fonction : Auteur
- PersonId : 793950
- ORCID : 0000-0002-8377-5965
Trine Nielsen
- Fonction : Auteur
- PersonId : 770024
- ORCID : 0000-0002-2066-7895
Sébastien André
- Fonction : Auteur
- PersonId : 1222777
- ORCID : 0000-0002-7543-153X
Rima Chakaroun
- Fonction : Auteur
- PersonId : 1194628
- ORCID : 0000-0001-9901-1815
Soraya Fellahi
- Fonction : Auteur
- PersonId : 1223960
- IdHAL : soraya-fellahi
- ORCID : 0000-0003-0086-4821
Joe-Elie Salem
- Fonction : Auteur
- PersonId : 777251
- IdHAL : joe-elie-salem
- ORCID : 0000-0002-0331-3307
- IdRef : 160947227
Torben Hansen
- Fonction : Auteur
- PersonId : 758676
- ORCID : 0000-0001-8748-3831
Serge Hercberg
- Fonction : Auteur
- PersonId : 1136672
- ORCID : 0000-0002-3168-1350
- IdRef : 02858709X
Marc-Emmanuel M.-E. Dumas
- Fonction : Auteur
- PersonId : 750569
- IdHAL : marc-emmanuel-dumas
- ORCID : 0000-0001-9523-7024
Fredrik Bäckhed
- Fonction : Auteur
- PersonId : 1194649
- ORCID : 0000-0002-4871-8818
Karine Clément
- Fonction : Auteur
- PersonId : 756892
- ORCID : 0000-0002-2489-3355
- IdRef : 07341512X
Résumé
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 .
| Origine | Publication financée par une institution |
|---|