Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
Authors: Molinaro Antonio , Bel Lassen Pierre , Henricsson Marcus , Wu Hao , Adriouch Solia , Belda Eugeni , Chakaroun Rima , Nielsen Trine , Bergh Per-Olof , Rouault Christine , André Sébastien , Marquet Florian , Andreelli Fabrizio , Salem Joe-Elie , Assmann Karen , Bastard Jean-Philippe , Forslund Sofia , Le Chatelier Emmanuelle , Falony Gwen , Pons Nicolas , Prifti Edi , Quinquis Benoit , Roume Hugo , Vieira-Silva Sara , Hansen Tue H. , Pedersen Helle Krogh , Lewinter Christian , Sønderskov Nadja B. ,   The MetaCardis Consortium, Alves Renato , Amouyal Chloe , Galijatovic Ehm Astrid Andersson , Barthelemy Olivier , Batisse Jean-Paul , Berland Magalie , Bittar Randa , Blottière Hervé , Bosquet Frederic , Boubrit Rachid , Bourron Olivier , Camus Mickael , Cassuto Dominique , Chilloux Julien , Ciangura Cecile , Coelho Luis Pedro , Collet Jean-Philippe , Dao Maria-Carlota , Djebbar Morad , Doré Angélique , Engelbrechtsen Line , Fellahi Soraya , Fezeu Leopold , Fromentin Sebastien , Giral Philippe , Gøtze Jens Peter , Hartemann Agnes , Holst Jens Juul , Hercberg Serge , Helft Gerard , Hornbak Malene , Hulot Jean-Sebastien , Isnard Richard , Jaqueminet Sophie , Jørgensen Niklas Rye , Julienne Hanna , Justesen Johanne , Kammer Judith , Krarup Nikolaj , Kerneis Mathieu , Khemis Jean , Kristensen Nadja Buus , Kuhn Michael , Lejard Véronique , Levenez Florence , Lucas-Martini Lea , Massey Robin , Maziers Nicolas , Medina-Stamminger Jonathan , Montalescot Gilles , Moutel Sandrine , Le Pavin Laetitia Pasero , Poitou Christine , Pousset Francoise , Pouzoulet Laurence , Schmidt Sebastien , Moitinho-Silva Lucas , Silvain Johanne , Sokolovska Nataliya , Touch Sothea , Svendstrup Mathilde , Swartz Timothy , Vanduyvenboden Thierry , Vatier Camille , Walther Stefanie , Køber Lars , Vestergaard Henrik , Hansen Torben , Zucker Jean-Daniel , Galan Pilar , Dumas Marc-Emmanuel , Raes Jeroen , Oppert Jean-Michel , Letunic Ivica , Nielsen Jens , Bork Peer , Ehrlich S. Dusko , Stumvoll Michael , Pedersen Oluf , Aron-Wisnewsky Judith , Clément Karine , Bäckhed Fredrik 
Published: November 2020

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.