Microbiota: relevant player in thiopurine metabolisation?

In this issue, Oancea et al1 demonstrate for the first time that gut microbiota is able to convert the thiopurine drug thioguanine into therapeutically active thiopurine nucleotides (TGN). They thereby open new perspectives for an optimised use of thiopurines in the treatment of patients with IBD and inspire the vision of topical thiopurine delivery to the inflamed gut. During the last years, our understanding of the molecular mechanisms, which underlie the well-known efficacy of thiopurines in IBD therapy, has been improved significantly. In order to allow potent therapeutic effects, classic thiopurine drugs including azathiopurine, mercaptopurine and thioguanine have to undergo metabolisation towards TGN. In particular, 6-thioguanine triphosphate (6-thio-GTP) could be identified as a crucial mediator of azathioprine-induced immunosuppressive effects in activated T cells and also in innate immune cells.2–4 Through its capacity to compete with endogenous GTP for the binding to...

Source: Gut - December 6, 2016 Category: Gastroenterology Authors: Atreya, I., Neurath, M. F. Tags: Commentaries Source Type: research