Imidazole propionate- a novel link between the human gut microbiota and development of insulin resistance in adipose tissue.

The gut microbiota affects numerous biological functions in the human body, and this has become an important field of research in biomedicine. Gut bacteria play a fundamental role in obesity, diabetes and cardiovascular disease.

Dysregulation of microbially derived metabolite production, in particular the production of imidazole propionate (ImP) was recently associated with metabolic disorders.

Specifically, ImP was shown to be increased in subjects with type 2 diabetes, and ImP was shown to impair glucose tolerance and reduce insulin signaling.

ImP is produced by a specific bacterial enzyme, called urocanate reductase (UrdA), which was recently structurally characterized by us.

Type 2 diabetes associated bacteria such as Streptococcus mutants and Eggerthella lentha has been verified to express UrdA and hence produce ImP. Thus, a direct link between the microbiota and type 2 diabetes has been established.

Thus, there is an urgent need to clarify the molecular mechanisms behind the production of ImP and to unravel the full mechanism of action of ImP in humans.

Hence, we are now setting out to perform a detailed structural and functional approach to disclose the molecular mechanisms behind the production of ImP as well as its consequences for human adipose tissue.

The good prospects for success are based on preliminary data already available in Lindkvist lab on the structure of UrdA, in combination with expertise and availability of human adipose tissue.