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Mechanisms of infectious diarrhea

Abstract

Infectious diarrhea is an important public health problem worldwide. Research has provided new insights into the mechanisms of diarrhea caused by various pathogens that are classified as noninflammatory, inflammatory or invasive. These three groups of organisms cause two diarrheal syndromes—noninflammatory diarrhea and inflammatory diarrhea. The noninflammatory diarrheas are caused by enterotoxin-producing organisms such as Vibrio cholerae and enterotoxigenic Escherichia coli, or by viruses that adhere to the mucosa and disrupt the absorptive and/or secretory processes of the enterocyte without causing acute inflammation or mucosal destruction. Inflammatory diarrhea is caused by two groups of organisms—cytotoxin-producing, noninvasive bacteria (e.g. enteroaggregative Escherichia coli, enterohemorrhagic Escherichia coli and Clostridium difficile), or by invasive organisms (e.g. Salmonella spp., Shigella spp., Campylobacter spp., Entamoeba histolytica). The cytotoxin-producing organisms adhere to the mucosa, activate cytokines and stimulate the intestinal mucosa to release inflammatory mediators. Invasive organisms, which can also produce cytotoxins, invade the intestinal mucosa to induce an acute inflammatory reaction, involving the activation of cytokines and inflammatory mediators. Regardless of the underlying mechanism they use, these various types of pathogen have all successfully evolved to evade and modulate the host defense systems. The mechanisms by which the different pathogens invade the host and cause infectious diarrhea are the topic of this Review.

Key Points

  • Infectious diarrhea is a global health problem and can be classified, based on the pathogenesis and clinical presentation, as noninflammatory diarrhea or inflammatory diarrhea

  • Various host factors protect against enteric infection, and enteropathogens must overcome these to cause disease

  • Common microbial causes of noninflammatory diarrhea are viruses, enterotoxin-producing organisms, Giardia lamblia and Cryptosporidium parvum

  • Enterotoxigenic Escherichia coli and Vibrio cholerae infections cause ADP ribosylation of Gs protein, whereas heat-stable enterotoxin-producing E. coli stimulate cGMP production; both E. coli and V. cholerae increase chloride secretion by crypt cells to produce watery diarrhea

  • Inflammatory diarrhea is caused by two groups of organisms: cytotoxin-producing, noninvasive bacteria (enteroaggregative E. coli, enterohemorrhagic E. coli, and Clostridium difficile); and invasive organisms (e.g. Salmonella spp., Shigella spp., Campylobacter jejuni)

  • Cytotoxin-producing organisms adhere to the mucosa, activate cytokines and stimulate the intestinal mucosa to release inflammatory mediators; invasive organisms, which can also secrete cytotoxins, invade the intestinal mucosa to induce an acute inflammatory reaction and activate cytokines and inflammatory mediators

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Figure 1: Schema illustrating mechanisms of pathogenesis for enterotoxin-mediated bacterial diarrheas.
Figure 2: Schema illustrating mechanisms of pathogenesis for invasive and cytotoxin-mediated bacterial inflammatory diarrheas.

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Navaneethan, U., Giannella, R. Mechanisms of infectious diarrhea. Nat Rev Gastroenterol Hepatol 5, 637–647 (2008). https://doi.org/10.1038/ncpgasthep1264

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