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

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

1 Sahlgrenska Academy at University of Gothenburg [Göteborg]
2 Nutriomics - Nutrition et obésités: approches systémiques (UMR-S 1269)
3 CRNH-IDF - Centre de Recherche en Nutrition Humaine d'Ile-de-France
4 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
5 Leipzig University / Universität Leipzig
6 CBMR - Novo Nordisk Foundation Center for Basic Metabolic Research
7 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
8 CHU Tenon [AP-HP]
9 Experimental and Clinical Research Center [Berlin, Germany]
10 MDC - Max Delbrück Center for Molecular Medicine [Berlin]
11 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
12 MICALIS - MICrobiologie de l'ALImentation au Service de la Santé
13 Rega Institute for Medical Research [Leuven, België]
14 UMMISCO - Unité de modélisation mathématique et informatique des systèmes complexes [Bondy]
15 EREN [CRESS - U1153 / UMR_A 1125] - Nutritional Epidemiology Research Team | Equipe de Recherche en Epidémiologie Nutritionnelle
16 NHLI - National Heart and Lung Institute [London]
17 Imperial College London
18 Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF)
19 Auteur indépendant
20 Chalmers University of Technology [Göteborg]
21 EMBL - European Molecular Biology Laboratory [Heidelberg]

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.

Domaines: Chimie; Sciences du Vivant [q-bio]

Antonio Molinaro, Pierre Bel Lassen, Marcus Henricsson, Hao Wu, Solia Adriouch, 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-03041270v1⟩