Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism

Eugeni Belda, Lise Voland, Valentina Tremaroli, Gwen Falony, Solia Adriouch, Karen E Assmann, Edi Prifti, Judith Aron-Wisnewsky, Jean Debédat, Tiphaine Le Roy, Trine Nielsen, Chloé Amouyal, Sébastien André, Fabrizio Andreelli, Matthias Blüher, Rima Chakaroun, Julien Chilloux, Luis Pedro Coelho, Maria Carlota Dao, Promi DasSoraya Fellahi, Sofia Forslund, Nathalie Galleron, Tue H Hansen, Bridget Holmes, Boyang Ji, Helle Krogh Pedersen, Phuong Le, Emmanuelle Le Chatelier, Christian Lewinter, Louise Mannerås-Holm, Florian Marquet, Antonis Myridakis, Veronique Pelloux, Nicolas Pons, Benoit Quinquis, Christine Rouault, Hugo Roume, Joe-Elie Salem, Nataliya Sokolovska, Nadja B Søndertoft, Sothea Touch, Sara Vieira-Silva, Pilar Galan, Jens Holst, Jens Peter Gøtze, Lars Køber, Henrik Vestergaard, Torben Hansen, Jens Nielsen, MetaCardis Consortium

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.

Original languageEnglish
Article number325753
JournalGut
Volume71
Issue number12
Pages (from-to)2463-2480
Number of pages18
ISSN0017-5749
DOIs
Publication statusPublished - Dec 2022

Keywords

  • Animals
  • Biotin/pharmacology
  • Diabetes Mellitus, Type 2
  • Gastrointestinal Microbiome
  • Humans
  • Inflammation
  • Mice
  • Mice, Inbred C57BL
  • Obesity, Morbid/surgery
  • Obesity/metabolism
  • Prebiotics
  • Vitamin B Complex/pharmacology

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