Nearly 500 million people worldwide have diabetes and around 90% of all cases are type 2 diabetes (T2D). Physical inactivity, obesity, and poor diet are risk factors for T2D. Interestingly, obesity and insulin resistance has been associated with the kynurenine pathway. Suggesting downstream metabolites may play a role in T2D. It is becoming increasing clear that changes in the microbiome can contribute to many diseases. In mice lacking IDO, microbial breakdown of tryptophan is observed, likely due to the increased availability of tryptophan. Therefore, the competition between host and microbiota for tryptophan might underpin the risk for diseases via shifts in downstream metabolites.
A recent study published by Dr. Qibin Qi et al. in Gut investigated host- and microbial-derived metabolites generated by the breakdown of tryptophan and the risk for T2D. T2D risk was associated with four host-derived metabolites (kynurenine, kynurenate, xanthurenate, and quinolinate) and one microbial-derived metabolite (indoleactate). Indolepropionate, a microbial-derived metabolite, has been associated with a reduced risk of T2D in other studies, and the authors of this study suggest that changes in the level of this metabolite underlies T2D. Not all bacterial species generate indole derivates however, 21 bacterial genera were associated with indolepropionate levels and of those, all but 5 were also associated dietary fiber intake. These bacteria were mostly Firmicutes, but also included some Actinobacteria and Bacteroides. These findings demonstrate the importance of diet and highlights why a poor diet (usually consisting of low fiber intake) is a risk factor for T2D. Furthermore, genetics plays a role in metabolism. Here, the authors show genetic variants that are associated with tryptophan metabolites, not surprisingly many were in genes involved in the metabolism or transport of TRP. Taken together, serum tryptophan metabolite levels may be used to identify individuals with an increased risk of T2D and it seems that targeting the microbiome through dietary changes has the potential to circumvent that risk.