If, on one side, anti-TNFα agents represent the mainstay in IBD therapy, also paradoxical GI adverse events for drugs neutralizing TNFα as well as the improvement of mucosal healing by TNFα during colitis have been reported over the past years (Bradford et al., 2017), reinforcing the notion of the Janus-faced role of this cytokine in intestinal inflammation (Dubé et al., 2015). This evidence concerns the gene TNF and inflammatory bowel disease.