Infective and inflammatory diarrhoea: mechanisms and opportunities for novel therapies

There have been significant advances in unravelling the cellular mechanisms of diarrhoea in common gut infections and colonic inflammation, as well as in the identification of targets for potential antidiarrhoeal drugs. Infective diarrhoea reflects activation of electrogenic Cl− secretion, inhibition of electroneutral NaCl absorption and in some cases, downregulation of tight junctional proteins and increased apoptosis. In colonic inflammation, diarrhoea mainly reflects impairment of colonic Na+ and Cl− absorption by inflammatory cytokines, leading to decreased water absorption. Stimulation of endogenous opiate-dependent pathways, manipulation of epithelial ion (Na+, K+ and Cl−) channels and suppression of proinflammatory cytokine production by a variety of drugs and novel molecules, offer opportunities to move evaluation of these potential antisecretory and anti-inflammatory agents from the laboratory into clinical trials.

► Infective diarrhoea reflects enhanced intestinal Cl− secretion across a ‘leakier’ gut.
► Inflammatory diarrhoea reflects cytokine-related impairment of colonic Na+, Cl− and water absorption.
► Endogenous opiates, ion channels and cytokines are targets for novel antidiarrhoeal drugs.