ER stress was reported to be regulated by three canonical signaling pathways: PERK‐eIF2α‐ATF4‐CHOP, IRE1‐XBP1, and ATF6‐ERAD, in various issues.34 Further, several studies have reported that the PERK‐eIF2α‐ATF4‐CHOP signaling pathway plays an essential role in ER stress‐induced apoptosis, especially in neuronal issues including spinal cord injury, subarachnoid hemorrhage injury, and cerebral ischemia injury.35, 36 In the present study, our data indicated consistent involvement of PERK‐eIF2α‐ATF4‐CHOP in ER stress‐induced apoptosis in CDI generated by PEL surgery. Here, XBP1 is linked to clostridium difficile infection.