a study of Hypervirulent Clostridioides difficile TcdB disrupts colic enteric nervous system function and structure via TFPI. Kai Zhang et al

The hypervirulent Clostridioides difficile (CD) is linked to severe clinical symptoms. The TcdB variant (TcdB2) produced by this strain causes significant damage to the colonic epithelium, but its effects on the enteric nervous system (ENS), which plays a key role in intestinal tract musculature control and content movement, are unknown. In this study, we assessed the effects of C. difficile TcdB2 on the structure and function of the ENS in mice. Adult mice treated with TcdB2 from C. difficile exhibited a reduction in colon motility and a loss of enteric neurons. Moreover, neural cells isolated from the intestine exhibited cytopathic effects in a time- and dose-dependent manner via the tissue factor pathway inhibitor (TFPI) receptor. These in vivo and in vitro findings together underscore the direct influence of TcdB on the structure and function of the ENS in Clostridioides difficile infection (CDI), providing novel insights into the mechanism of CDI.