Infectious diarrhea: Cellular and molecular mechanisms.

Diarrhea caused by enteric infections is a major factor in morbidity and mortality worldwide. An estimated 2-4 billion episodes of infectious diarrhea occur each year and are especially prevalent in infants. This review highlights the cellular and molecular mechanisms underlying diarrhea associated with the three classes of infectious agents, i.e., bacteria, viruses and parasites. Several bacterial pathogens have been chosen as model organisms, including Vibrio cholerae as a classical example of secretory diarrhea, Clostridium difficile and Shigella species as agents of inflammatory diarrhea and selected strains of pathogenic Escherichia coli (E. coli) to discuss the recent advances in alteration of epithelial ion absorption. Many of the recent studies addressing epithelial ion transport and barrier function have been carried out using viruses and parasites. Here, we focus on the rapidly developing field of viral diarrhea including rotavirus, norovirus and astrovirus infections. Finally we discuss Giardia lamblia and Entamoeba histolytica as examples of parasitic diarrhea. Parasites have a greater complexity than the other pathogens and are capable of creating molecules similar to those produced by the host, such as serotonin and PGE(2). The underlying mechanisms of infectious diarrhea discussed include alterations in ion transport and tight junctions as well as the virulence factors, which alter these processes either through direct effects or indirectly through inflammation and neurotransmitters.