Fettucciari et al. also showed that pro-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) plus interferon-gamma (IFN-γ) (CKs) strongly enhanced TcdB-induced apoptosis [10,23] by increasing the activation of the three apoptotic pathways each mediated by calpains, caspases, and cathepsins (Figure 1) [23] and this phenomenon could have an important implication on CDI pathogenesis, CDI relapses, IBS and IBD [72,73,74,125,126]. This evidence concerns the gene TNF and irritable bowel syndrome.