Dietary L-Tryptophan consumption determines the number of colonic regulatory T cells and susceptibility to colitis via GPR15.

Environmental factors are the major contributor to the onset of immunological disorders such as ulcerative colitis. However, their identities remain unclear. Here, we discover that the amount of consumed L-Tryptophan (L-Trp), a ubiquitous dietary component, determines the transcription level of the colonic T cell homing receptor, GPR15, hence affecting the number of colonic FOXP3+ regulatory T (Treg) cells and local immune homeostasis. Ingested L-Trp is converted by host IDO1/2 enzymes, but not by gut microbiota, to compounds that induce GPR15 transcription preferentially in Treg cells via the aryl hydrocarbon receptor. Consequently, two weeks of dietary L-Trp supplementation nearly double the colonic GPR15+ Treg cells via GPR15-mediated homing and substantially reduce the future risk of colitis. In addition, humans consume 3-4 times less L-Trp per kilogram of body weight and have fewer colonic GPR15+ Treg cells than mice. Thus, we uncover a microbiota-independent mechanism linking dietary L-Trp and colonic Treg cells, that may have therapeutic potential.

Confirmation of direct epidural catheter placement using nerve stimulation in pediatric anesthesia.

UNLABELLED: We evaluated the success rate of using low current electrical stimulation (the Tsui test) to identify and confirm direct epidural catheter placement in a pediatric population. Thirty subjects received a standard anesthetic and administration of the Tsui test on epidural placement. The distribution of myotomal activity was recorded. The intended and actual level of the epidural catheter was compared. Myotomal activity was seen in all patients but one. The median current resulting in myotomal activity was 5.3 mA. The median difference between the intended and actual level as confirmed on radiograph was 1.8 levels. The clinical success rate was 93.9%. The positive predictive value of the Tsui test was 82%; i.e., in 23 of 28 cases, the Tsui test correctly identified the position of the epidural catheter tip within 2 vertebral levels. The test did not offer any added advantage when used in the setting of directly placed epidural catheters in our institution over "blind" methods already used to confirm catheter position when using cutaneous landmarks and test dosing. IMPLICATIONS: A new technique to confirm epidural catheter position uses low current electrical stimulation in pediatric patients. This study evaluated the use of electrical stimulation in 30 pediatric patients for directly placed catheters. Electrical stimulation did not provide any advantage over conventional methods (e.g., cutaneous landmarks) for confirmation of catheter position.