Enteric infections, diarrhea, and their impact on function and development
William A. Petri Jr., Mark Miller, Henry J. Binder, Myron M. Levine, Rebecca Dillingham, Richard L. Guerrant
William A. Petri Jr., Mark Miller, Henry J. Binder, Myron M. Levine, Rebecca Dillingham, Richard L. Guerrant
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Review Series

Enteric infections, diarrhea, and their impact on function and development

Abstract

Enteric infections, with or without overt diarrhea, have profound effects on intestinal absorption, nutrition, and childhood development as well as on global mortality. Oral rehydration therapy has reduced the number of deaths from dehydration caused by infection with an enteric pathogen, but it has not changed the morbidity caused by such infections. This Review focuses on the interactions between enteric pathogens and human genetic determinants that alter intestinal function and inflammation and profoundly impair human health and development. We also discuss specific implications for novel approaches to interventions that are now opened by our rapidly growing molecular understanding.

Authors

William A. Petri Jr., Mark Miller, Henry J. Binder, Myron M. Levine, Rebecca Dillingham, Richard L. Guerrant

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Figure 3

Movement of Na+ and Cl– in the small intestine.

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Movement of Na+ and Cl– in the small intestine. (A) Move...
(A) Movement in normal subjects. Na+ is absorbed by two different mechanisms in absorptive cells from villi: glucose-stimulated absorption and electroneutral absorption (which represents the coupling of Na/H and Cl/HCO3 exchanges). (B) Movement during diarrhea caused by a toxin and inflammation. In toxigenic diarrhea (caused, for example, by the enterotoxin produced by V. cholerae), increased mucosal levels of cAMP inhibit electroneutral NaCl absorption but have no effect on glucose-stimulated Na+ absorption. In inflammatory diarrhea (e.g., following infection with Shigella spp. or Salmonella spp.) there is extensive histological damage, resulting in altered cell morphology and reduced glucose-stimulated Na+ and electroneutral NaCl absorption. The role of one or more cytokines in this inflammatory response is critical. In secretory cells from crypts, Cl– secretion is minimal in normal subjects and is activated by cAMP in toxigenic and inflammatory diarrhea.