Diet plays a major role in the composition of our gut microbiota. From what we consume, the gut bacteria produce organic compounds known as metabolites, which can affect our health. © Adobe Stock
An imbalanced diet has been linked to a disruption of the gut microbiota, which promotes metabolic diseases such as diabetes. Researchers from Inserm, Sorbonne Université, Paris hospitals group AP-HP and the French National Research Institute for Agriculture, Food and Environment (INRAE) in collaboration with a Swedish team have shown, in a large European cohort, that changes in the composition of the gut microbiota lead to increased blood levels of the molecule imidazole propionate. A molecule known to render the body’s cells resistant to insulin, thereby increasing the risk of developing type 2 diabetes. Their findings have been published in Nature Communications.
Diet plays a major role in the composition of our gut microbiota. From what we consume, the gut bacteria produce organic compounds known as metabolites, which can affect our health if they are present in too large or too small a quantity in our body.
Other recent research suggests that an alteration of the gut microbiota disrupts the metabolism of histidine, an amino acid found in many foods, leading to increased levels of the metabolite imidazole propionate. This molecule blocks the action of insulin, preventing it from lowering blood glucose levels.
The present study published in Nature Communications confirms these initial findings in a large European cohort of 1990 participants from France, Germany and Denmark, called METACARDIS. Coordinated by Inserm, the objective of this cohort is to study the impact of changes in the gut microbiota on the onset and progression of cardiometabolic diseases and associated pathologies. “METACARDIS is a unique and valuable database in that it allows us to access very detailed characteristics of each person enrolled in the cohort with large amounts of phenotypic, metabolic, and bacterial genetic data,” emphasizes the project’s coordinator, physician Karine Clément, teacher-researcher in nutrition at Sorbonne Université.
She and her colleagues show that in the cohort, subjects with prediabetes or type 2 diabetes do indeed have higher levels of imidazole propionate in their blood. The gut microbiota of these subjects is also characterized by a significant depletion of bacteria.
“Our study suggests that people with poor diets have increased levels of imidazole propionate and that there is a clear link between the depleted composition of the microbiota, diet and type 2 diabetes. Its aim is to convey a message of prevention, emphasizing that a more varied diet can enrich the microbiota. This study also has therapeutic implications since we could envisage the future development of drugs to modify the synthesis of certain metabolites such as imidazole propionate,” explains Clément.
A number of questions continue to be raised and are expected to be elucidated in future research based on METACARDIS. In particular, the researchers want to understand how the elevation of one or more metabolites can predict, in people with diabetes, the risk of developing other complications, such as those affecting the cardiovascular system. They also want to study how increased imidazole propionate levels in people with prediabetes could increase their risk of developing type 2 diabetes earlier on in their clinical course.
This large-scale research project, based on close collaboration between several European scientific teams, has received support from the European Community (7th Framework Programme FP7-Metacardis), as well as from the Leducq Foundation.
 Prediabetes is a blood glucose disorder at a less advanced stage than diabetes itself. It is characterized by fasting blood glucose levels of between 1.10 g/L and 1.25 g/L (normal fasting blood glucose is below 1.10 g/L). The risk of going on to develop type 2 diabetes is increased.
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Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
Antonio Molinaro 1 2*, Pierre Bel Lassen 3 4*, Marcus Henricsson 1, Hao Wu 1, Solia Adriouch 3, Eugeni Belda 3 5, Rima Chakaroun 6, Trine Nielsen 7, Per-Olof Bergh 1, Christine Rouault 3, Sébastien André 3, Florian Marquet 3, Fabrizio Andreelli 3, Joe-Elie Salem 8, Karen Assmann 3, Jean-Philippe Bastard 9, Sofia Forslund 10, Emmanuelle Le Chatelier 11, Gwen Falony 12 13, Nicolas Pons 11, Edi Prifti 5 14, Benoit Quinquis 11, Hugo Roume 11, Sara Vieira-Silva 12 13, Tue H Hansen 7, Helle Krogh Pedersen 7, Christian Lewinter 7, Nadja B Sønderskov 7, MetaCardis Consortium; Lars Køber 7, Henrik Vestergaard 7, Torben Hansen 7, Jean-Daniel Zucker 14, Pilar Galan 15, Marc-Emmanuel Dumas 16 17, Jeroen Raes 12, Jean-Michel Oppert 4, Ivica Letunic 18, Jens Nielsen 19, Peer Bork 20 21, S Dusko Ehrlich 11, Michael Stumvoll 6, Oluf Pedersen 7, Judith Aron-Wisneswky 3,4, Karine Clément 3,4*, Fredrik Bäckhed 1,2*
Nature Communications, Novembre 2020.