Probiotic strain released-carbamoyl phosphates modify corticosterone metabolism on colonic epithelial cells by elevating 11-beta-hydroxysteroid dehydrogenase isozyme 2

Chronic psychological stress contributes to functional disorder development, including irritable bowel syndrome (IBS). Although probiotics have shown potential in ameliorating these disorders, the precise mechanisms remain incompletely understood. The aim of this study was to elucidate the mechanism underlying the effect of Lacticaseibacillus paracasei strain Shirota (LcS) on the host anti-stress response in a colonic epithelial cell line. The expression of the stress hormone-degrading enzyme, 11 β-hydroxysteroid dehydrogenase type 2 ( Hsd11b2 ), was suppressed by corticosterone and restored by LcS treatment. Fractionation of the LcS culture supernatant revealed a derivative of carbamoyl phosphate as the key factor responsible for inducing Hsd11b2 . Moreover, activation of acetylcholine receptor and inhibition of NF-κB p50 homodimer nuclear translocation were required to induce Hsd11b2 in colonic epithelial cells. These findings reveal a novel probiotic mechanism whereby an LcS metabolite triggers anti-stress responses, including Hsd11b2 induction, by modulating the acetylcholine and NF-κB pathways. This new mechanism by which probiotics can stimulate anti-stress effects in the colonic mucosa may contribute to IBS treatment.