 In 2001, researchers from ICDDRB and Karolinska Institute BA reported in Nature Medicine a down regulation of LL-37 and human Beta-defensin-1 HBD-1 in the epithelial cells in diarrhoea caused by Shigella dysenteriae type I and other enteric bacteria 21. This down regulation could be reproduced in vitro by using the cell lines U937 of monocyte origin and HT-29 of colonic epithelial origin, when infected with Shigella or plasmid DNA derived from Shigella. The down regulation can be an important immune escape mechanism for pathogens to avoid potent mucosal effector molecules such as antimicrobial peptides. Since antimicrobial factors drench the mucosal surfaces, it is conceivable that pathogenic bacteria down-regulate the front line defenses of humans as a part of their invasive process. Therefore, a novel approach will be to block this down-regulation or to take a therapeutic approach to up-regulate the production of endogenous antimicrobials. Recent studies have shown that short chain fatty acids SCFA can up-regulate expression of LL-37 in colonic epithelial cells, and among them sodium butyrate was the best inducer 22, 23. Moreover, butyrate induces colonic cell differentiation that has been reported to be a key determinant of LL-37 expression in human colon epithelium 22. However, it was shown that pathways other than those involved in cell differentiation are involved in the up-regulation of LL-37 with butyrate 23. Butyrate is produced in the colon by fermentation of dietary fibre. Thus, there is a link between the normal gut flora and the expression of endogenous antibiotics. Additionally, SCFAs including butyrate has been shown to reduce clinical symptoms, and alter microbiological and pathological features in experimental Shigella infections in rabbit models 24. Thus, a relationship between the severity of Shigella infections and mucosal levels of antimicrobial peptides is conceivable. Oral administration of sodium butyrate to rabbits infected with Shigella showed up-regulation of CAP-18 rabbit homologue of LL-37 in the colonic epithelial cells with a concomitant reduction in shigella load in stool and clinical recovery Raqib et al, manuscript accepted. Preventing down-regulation or enhancing antimicrobial peptide expression could provide an alternative treatment in protecting humans and animal livestock against bacterial pathogens. These studies may provide a basis for therapeutic manipulation of endogenous antimicrobial peptides including LL-37 expression in vivo using dietary substances or butyrate to strengthen the epithelial defense barrier. Therefore, we have initiated a clinical study in ICDDRB to evaluate the efficacy of butyrate enema in the treatment of shigellosis. 