Psychological Stressinduced Systemic Corticosterone Directly Sabotages Intestinal Stem Cells And Exacerbates Colitis Xiaole Sheng Lanfei Jin Zhengrong Yao Jiaji Gu Longtao Zhu Andi Huang Junxuan Peng Xin Xu Xiaolong Ge Wei Zhou Jinghao Sheng Zhengping Xu Rongpan Bai by Xiaole Sheng & Lanfei Jin & Zhengrong Yao & Jiaji Gu & Longtao Zhu & Andi Huang & Junxuan Peng & Xin Xu & Xiaolong Ge & Wei Zhou & Jinghao Sheng & Zhengping Xu & Rongpan Bai instant download after payment.

Psychological stress has profound impacts on the gastrointestinal tract via the brain‒gut axis. However, its effects on intestinal stemcells (ISCs) and the resulting implication for intestinal homeostasis remain poorly understood. Here, we observed a notablereduction in both the quantity and proliferative capacity of ISCs under chronic stress conditions, driven by elevated levels ofcorticosterone resulting from activation of the hypothalamic‒pituitary‒adrenal (HPA) axis. Mechanistically, corticosterone directlyinteracts with its receptor, nuclear receptor subfamily 3 group c member 1 (NR3C1), leading to increased expression of FKBP prolylisomerase 5 (FKBP5) in ISCs. Subsequently, FKBP5 negatively regulates AKT activation by facilitating its dephosphorylation atSer473, ultimately enhancing nuclear translocation of forkhead box O (FoxO) and inhibiting ISC proliferative activity. Consequently,1234567890();,:ISC dysfunction contributes to the stress-driven exacerbation of DSS-induced colitis. Collectively, these findings reveal an intrinsicbrain-to-gut regulatory pathway whereby psychological stress impairs ISC activity via corticosterone elevation, providing amechanistic explanation for stress-enhanced susceptibility to colitis.Cell Discovery;