Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
Antonio Molinaro, Pierre Bel Lassen, Marcus Henricsson, Hao Wu, Solia Adriouch, Eugeni Belda, Rima Chakaroun, Trine Nielsen, Per-Olof Bergh, Christine Rouault, Sébastien André, Florian Marquet, Fabrizio Andreelli, Joe‐Elie Salem, Karen E. Assmann, Jean‐Philippe Bastard, Sofia K. Forslund, Emmanuelle Le Chatelier, Gwen Falony, Nicolas Pons, Edi Prifti, Benoît Quinquis, Hugo Roume, Sara Vieira‐Silva, Tue H. Hansen, Helle Pedersen, Christian Lewinter, Nadja B. Sønderskov, Renato Alves, Chloé Amouyal, Ehm Astrid Andersson Galijatovic, Olivier Barthélemy, Jean-Paul Batisse, Magali Berland, Randa Bittar, Hervé M. Blottière, F Bosquet, Rachid Boubrit, Olivier Bourron, Mickaël Camus, Dominique Adèle Cassuto, Julien Chilloux, Cécile Ciangura, Luís Pedro Coelho, Jean‐Philippe Collet, Maria Carlota Dao, Morad Djebbar, Angélique Doré, Line Engelbrechtsen, Soraya Fellahi, Léopold Fezeu, Sébastien Fromentin, Philippe Giral, Jens Peter Gøtze, A. Hartemann, Jens J. Holst, Serge Herçberg, Gérard Helft, Malene Hornbak, Jean‐Sébastien Hulot, Richard Isnard, Sophie Jaqueminet, Niklas Rye Jørgensen, Hanna Julienne, Johanne Justesen, Judith Kammer, Nikolaj T. Krarup, Mathieu Kernéis, Jean Khémis, Nadja Buus Kristensen, Michael Kuhn, Véronique Lejard, Florence Levenez, Lea Lucas-Martini, Robin Massey, Nicolas Maziers, Jonathan Medina-Stamminger, Gilles Montalescot, Sandrine Moutel, Laetitia Pasero Le Pavin, Christine Poitou, Françoise Pousset, Laurence Pouzoulet, Sebastien Schmidt, Lucas Moitinho‐Silva, Johanne Silvain, Nataliya Sokolovska, Sothea Touch, Mathilde Svendstrup, T.D. Swartz, Thierry Vanduyvenboden, Camille Vatier, Stefanie Walther, Lars Køber, Henrik Vestergaard, Torben Hansen, Jean‐Daniel Zucker, Pilar Galán, Marc‐Emmanuel Dumas, Jeroen Raes
Abstract
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.