Microbial toxins and diarrhoeal diseases: introduction and overview

Without question, diarrhoeal diseases constitute one of the greatest causes of morbidity and death on a global scale. To an increasingly recognized extent, they are caused by an expanding array of microbial products or "toxins'. The symposium focuses on microbial products that alter normal bowel function either by augmenting secretory pathways or by selectively destroying mucosal cells or pathways, thus leading to an imbalance in the concert of normal absorptive function that results in diarrhoea. An understanding of normal intestinal physiology is thus the key to unraveling the specific actions of microbial toxins. In many instances, the microbial toxins are themselves providing unique pharmacological tools with which to dissect normal intestinal function. Specifically, families of enterotoxins are reviewed that appear to cause secretion through the recognized second messengers of cyclic AMP and cyclic GMP as well as cyclic nucleotide-independent and calcium-dependent pathways. Potential "third messengers' such as the protein kinases, through which one or more of the second messengers may act, are also considered. We examine cytotoxins that alter the orchestrated function of specialized regions of intact intestinal mucosa by selectively impeding or killing certain cells, so leading to small intestinal or colonic pathology and contributing to diarrhoea. We also consider a wide range of recognized bacterial and parasitic agents and their enterotoxic products. In some instances, these toxins may strikingly resemble our own endogenous humoral regulators or hormones. At this point, the possible roles of viruses or other transmissible genome products in this area await further clarification. Finally, we examine pharmacological and immunological approaches to attacking the toxins themselves or the deranged physiology they cause, in order to approach the control of the potentially devastating diseases of diarrhoea.