Focus on the role of antimicrobial peptides

Defensins play a major role in innate immunity. Ten defensins have been identified in humans: six α-defensins that are mainly secreted by Paneth cells, neutrophils and some populations of small intestine macrophages; and four β-defensins that are secreted by epithelial cells.⁵

Mechanisms of action

Mechanisms of action of antimicrobial peptides are variable:⁸ some puncture bacterial membranes and cause ion and nutrient efflux, loss of structure, or even bacterial lysis; other “bind” to bacteria and limit they passage through the gut epithelium without killing them; in other words, they reduce pathogen colonization and change the composition and density of bacterial communities in the intestinal lumen.

Crohn's disease and decrease in defensins

When CD affects the ileum, the production of some α-defensins decreases, which reduces antibacterial activity and promotes pathogenic bacteria penetration⁵. Among possible explanations there is NOD² gene mutation, involved in the recognition of bacterial surface and onset of defensin production; and impaired signaling pathways, whose dysregulation is involved in the development of many human cancers. Some researchers believe that the decrease in α defensin content is not the cause but the consequence of inflammation.⁴ In colonic CD, only β-defensin rates are disrupted5: increase in secretion of β-defensin type 2 and decrease in type 1. Some scientists believe that the smaller number of copies of the gene located on chromosome 8 in affected patients (3 instead of 4) is at fault.