Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Pierre Bel Lassen (1, 2) , Trine Nielsen (3) , Per-Olof Bergh (4) , Christine Rouault (1) , Sébastien André (1) , Florian Marquet (1) , Fabrizio Andreelli (1) , Joe-Elie Salem (5) , Karen Assmann (1) , Jean-Philippe Bastard (6) , Sofia Forslund (7, 8, 9) , Emmanuelle Le Chatelier (10) , Gwen Falony (11) , Nicolas Pons (10) , Edi Prifti (12, 13) , Benoit Quinquis (10) , Hugo Roume (10) , Sara Vieira-Silva (11) , Tue Hansen (3) , Helle Krogh Pedersen (3) , Christian Lewinter (3) , Nadja Sønderskov (3) , Henrik Vestergaard (3) , Jeroen Raes (10, 11) , Jens Nielsen (14) , Peer Bork (15) , S. Dusko Ehrlich (10) , Oluf Pedersen (3) , Judith Aron-Wisneswky (1, 2) , Karine Clément (1, 2) , Fredrik Bäckhed (3, 4) , Antonio Molinaro (4) , Pierre Bel Lassen , Marcus Henricsson (4) , Hao Wu (4) , Solia Adriouch (1) , Eugeni Belda (1, 12) , Rima Chakaroun (16) , Trine Nielse (3) , Christine Bergh , Sébastien Rouault , Florian Andr , Fabrizio Marquet , Joe-Elie Andreelli , Karen Salem , Jean-Philippe Assmann , Sofia Bastard , Emmanuelle Forslund , Gwen Le Chatelier , Nicolas Falon , Edi Pons , Benoit Prift , Hugo Quinquis , Sara Roume , Tue H Vieira-Silv , Krogh Hansen , Christian Pedersen , Nadja B Lewinter , Metacardis The , Lars Køber (3) , Henrik Vestergaar , Torben Hansen (3) , Jean-Daniel Zucker (13) , Pilar Galan (17) , Marc-Emmanuel Dumas (18, 19) , Jeroen Rae (10) , Jean-Michel Oppert (20) , Ivica Letunic (21) , Jens Nielse , S Dusko Ehrlic (10) , Michael Stumvoll (16) , Oluf Pederse , Judith Aron-Wisnewsky , Karine Clément , Fredrik Bäckhe

1 Nutriomics - Nutrition et obésités: approches systémiques (UMR-S 1269)
2 CRNH-IDF - Centre de Recherche en Nutrition Humaine d'Ile-de-France
3 CBMR - Novo Nordisk Foundation Center for Basic Metabolic Research
4 Sahlgrenska Academy at University of Gothenburg [Göteborg]
5 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
6 CHU Tenon [AP-HP]
7 Experimental and Clinical Research Center [Berlin, Germany]
8 MDC - Max Delbrück Center for Molecular Medicine [Berlin]
9 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
10 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
11 Rega Institute for Medical Research [Leuven, België]
12 Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN]
13 UMMISCO - Unité de modélisation mathématique et informatique des systèmes complexes [Bondy]
14 Chalmers University of Technology [Göteborg]
15 EMBL - European Molecular Biology Laboratory [Heidelberg]
16 Universität Leipzig [Leipzig]
17 CRESS - U1153 - Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle
18 NHLI - National Heart and Lung Institute [London]
19 Imperial College London
20 Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF)
21 Biobyte Solutions GMBH

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.

Domains: Chemical Sciences; Life Sciences [q-bio]

Pierre Bel Lassen, Trine Nielsen, Per-Olof Bergh, Christine Rouault, Sébastien André, et al.. Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology. Nature Communications, 2020, 11 (1), ⟨10.1038/s41467-020-19589-w⟩. ⟨hal-03041270v2⟩