Thus, disruptions of L-arg metabolism have been associated with a variety of disorders affecting intestinal permeability and the outgrowth of pathogenic/pathobiontic microorganisms, including IBD, NEC, severe infections, or sepsis (Table 1).13,26−28,43−56,68−71 However, L-arg is not only an integral component of the host defense and a crucial modulator of immune responses, but also directly affects bacterial virulence and pathogenesis.94 Not only free L-arg, but also arginine-residues in proteins play fundamental roles in these latter processes. Here, ARHGEF12 is linked to necrotizing enterocolitis.