IDO inhibitors to treat metabolic disorders: a new gut microbiota-mediated potential therapy
Studies published in Nature Medicine propose indoleamine 2,3-dioxygenase (IDO) as a potential therapeutic target. IDO influences the tryptophan metabolism exercing a microbiota-dependent control with major consequences on the metabolic disease:
Obesity is associated with an increase of intestinal indoleamine 2,3-dioxygenase activity, which shifts tryptophan metabolism from indole derivative and interleukin-22 production toward kynurenine production. Indoleamine 2,3-dioxygenase deletion or inhibition improves insulin sensitivity, preserves the gut mucosal barrier, decreases endotoxemia and chronic inflammation, and regulates lipid metabolism in liver and adipose tissues.
The studies in mice described in this work demonstrate these effects of the IDO inhibition and, moreover, the authors also observe a similar shift of tryptophan metabolism in obese or diabetic patients comparing with non-obese subjects. This suggests a specific microenvironmental regulation of IDO in intestine of subjects with obesity that indicates that high levels of kynurenine in plasma and feces are associated with a pathologic metabolic profile.
These findings open a new research line focused in the possible use of IDO inhibitors in patients with cardiometabolic diseases.