If asked how we currently treat a bacterial infection such as Shigella dysentery, most informed individuals would offer that we administer antibiotics. Our informed individual would add that we must also restore the losses of water and salts leaving the body as diarrhea, most likely with an appropriately designed ‘‘oral rehydration’’solution. But to halt the infection itself, surely we must either treat shigellosis with antibiotics or let the infection run its course. By ‘‘run its course,’’we mean simply that if we can hold off giving antibiotics long enough, the adaptive immune system will eventually assemble the macrophages, lymphocytes, and antibodies capable of fighting off this organism. Unfortunately, many children die waiting for the ‘‘sluggish’’adaptive immune system to do its thing. Furthermore, overuse of antibiotics has resulted in the emergence of drug-resistant strains of Shigella in countries besieged with dysentery (1).

In this issue of PNAS, Raqib et al.(2) offer a radical and revolutionary alternative to our conventional way of thinking about the treatment of acute infectious diseases. They suggest that a disease such as shigellosis can be treated by stimulating the epithelial lining of the colon and rectum to produce an endogenous antimicrobial peptide (AMP) that kills Shigella. The ‘‘therapeutic’’-inducing substance is sodium butyrate, the salt of a short-chain fatty acid normally produced in the colon, itself hardly antibacterial, and a substance that appears to be effective when administered by mouth.