FIG 1.

Possible scenario for impacts of the NSAID indomethacin on the up-modulation of 15-hydroxyprostaglandin dehydrogenase (Hpgd, 15-PGDH) expression and alteration of the gut microbiota, which disrupt the tight junctions (TJs) of intestinal epithelial cells to allow the translocation of bacteria and their metabolites into the bloodstream. In parallel, Clostridium difficile and its TcdA and TcdB toxins can induce the proinflammatory response that triggers the induction of inducible cyclooxygenase 2 (COX-2), leading to enhancement of prostaglandin E2 (PGE2) production.