The kynurenine pathway is the major

The kynurenine pathway is the major route for TRP me- tabolism, in which indoleamine 2,3-dioxygenase (IDO) converts TRP to KYN [46]. In the current study, the rise in the KYN/TRP ratio in HA rats treated with probiotics may indicate that probiotics enhance IDO activity. IDO is ex- pressed in various cell types, and is widely involved in im- munomodulatory activity [47], such as anti-inflammatory effect and protective role in a mouse model of colitis [48]. Therefore, in the present study, improved anxiety-like be- havior in probiotic treatment of HA rats may be a result of an immunomodulatory effect of this treatment through en- hanced IDO activity, the promotion of TRP depletion, and reduction of 5-HT metabolism. Similarly in another study, attenuation of the allergic airway response was found to be due to an increase in systemic IDO activity induced by administration of live Lactobacillus reuteri [49]. However, our results are contradicted by other studies that have shown suppression of IDO production in response to treatment of the probiotic Bifidobacterium species or Lactobacillus johnsonii in a rat model of depression [25,50]. In the mouse model of allergic airway inflammation, it is important to note that the IDO activity was enhanced only following the administration of Lactobacillus reuteri but not Lactobacil- lus salivarius [49]. These data suggest that different probi- otic species or strains may have different effects on IDO activity. Furthermore, KA produced from KYN has been shown to enhance anxiety because it can decrease the ex- tracellular level of glutamate [51,52]. Results from our study show an increase in the KA/KYN ratio in HA rats but a decrease of that following probiotic treatment, thus providing further evidence for the potential anxiolytic prop- erties of the probiotic L. helveticus strain NS8.