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  • Review Article
  • Published:

Enteric infection meets intestinal function: how bacterial pathogens cause diarrhoea

Nature Reviews Microbiology volume 7, pages 110–119 (2009)Cite this article

Key Points

  • Great advances have been made in understanding the adherence and virulence factors of enteric pathogens, the basic physiology of the intestine and the role of innate immunity in health and disease. This Review focuses on the primary links between enteric bacterial pathogens and diarrhoea.

  • Whereas the effect of cholera toxin on cystic fibrosis transmembrane regulator-dependent chloride and fluid secretion is well established, recent studies have uncovered the mechanisms by which the toxin finds its way from the bacterium into the host cell cytosol.

  • Bacteria that do not typically produce toxins can also alter various ion transporters on intestinal epithelial cells. The majority of work in this regard pertains to enteropathogenic Escherichia coli. The effect of enteropathogenic E. coli effector molecules (secreted through its type III secretion system) on specific epithelial cell ion transporters is discussed.

  • Tight junctions are composed of several proteins that together form a regulatable paracellular barrier to fluid and electrolytes, and also facilitate vectorial transport by maintaining distinction between the apical and basolateral sides of the epithelial monolayer (fence function). Several enteric pathogens disrupt tight junctions, and perturb barrier and fence functions. The relationship between these effects and diarrhoea is explored.

  • Intestinal pathogens encounter, and often manipulate, the innate immune system. This is an active area of investigation and is providing fundamental insights about the mammalian innate immune system. The relationship between bacterium-induced inflammation and diarrhoea is not clear; nevertheless, some speculations can be made on the basis of recent studies.

  • The ancient art of using bacteria to fight bacteria, namely the use of probiotic organisms for therapeutic interventions, is being actively explored. Moreover, advances in related areas are allowing the exploration of the scientific basis for the beneficial effects of probiotic organisms. Some current Phase III clinical trials are exploring the applicability of these approaches to combat diarrhoeal illnesses worldwide.

Abstract

Infectious diarrhoea is a significant contributor to morbidity and mortality worldwide. In bacterium-induced diarrhoea, rapid loss of fluids and electrolytes results from inhibition of the normal absorptive function of the intestine as well as the activation of secretory processes. Advances in the past 10 years in the fields of gastrointestinal physiology, innate immunity and enteric bacterial virulence mechanisms highlight the multifactorial nature of infectious diarrhoea. This Review explores the various mechanisms that contribute to loss of fluids and electrolytes following bacterial infections, and attempts to link these events to specific virulence factors and toxins.

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Figure 1: The 7 metre-long human intestine absorbs nutrients and forms a barrier to luminal contents.
Figure 2: Mechanisms by which enteric pathogens cause diarrhoea.
Figure 3: Cl− secretion by intestinal epithelial cells is stimulated through the activation of cyclic AMP or Ca2+.
Figure 4: Enteropathogenic Escherichia coli (EPEC) alter apical Na+, Cl− and glucose absorption.

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Acknowledgements

These studies were supported by the AGA bridging award and the University of Illinois at Chicago gastrointestinal and liver disease (GILD) council (to V.K.V.), grants DK-50694, DK-58964 and DK067887 from the National Institutes of Health, and the Veterans Affairs Merit Review (G.H.).

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Author notes

  1. V. K. Viswanathan, Kim Hodges and Gail Hecht: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Veterinary Science & Microbiology, University of Arizona, Tucson, 85721, Arizona, USA

    V. K. Viswanathan

  2. Department of Medicine, Section of Digestive Diseases and Nutrition, University of Illinois and Jesse Brown Veterans Affairs Medical Center, Chicago, 60612, Illinois, USA

    Kim Hodges & Gail Hecht

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  1. V. K. Viswanathan
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Correspondence to Gail Hecht.

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DATABASES

Entrez Genome Project

Citrobacter rodentium

Salmonella enterica serovar Typhimurium

Shigella flexneri

Vibrio parahaemolyticus

OMIM

congenital chloride diarrhoea

FURTHER INFORMATION

Gail Hecht's homepage

Glossary

Diarrhoea

A disorder manifested by frequent evacuation of excessively fluid faeces.

Enteric pathogen

A pathogen whose primary target is the gastrointestinal tissue.

Commensal

An organism that derives food or other benefits from another organism without harming it.

Lamina propria

The layer of mucosal tissue directly below the epithelial cell monolayer; various cell types including those involved in immunity reside here.

Tight junctions

Also known as kissing junctions, these lipid–protein complexes at the apical junctions of epithelial cells form a regulatable barrier, selectively allowing the passage of ions and electrolytes.

Adherens junctions

Present at the contact point between epithelial cells, these serve as anchor points for cytoskeletal filaments made of actin (microfilaments).

Desmosomes

Intercellular junctions typically present in tissues subject to mechanical stress. The adhesion molecules in this region serve as a tether for cytoskeletal filaments known as intermediate filaments (for example, cytokeratins).

Microbiome

The totality of microbial species living in a specific organism.

AB5 toxins

Bacterial toxins that have the structural composition of a single catalytically active A subunit and a pentamer of B subunits. The B subunits are involved in receptor binding and deliver the A subunit to the target cells.

Attaching and effacing

Attaching and effacing pathogens are a group of enteric pathogens that includes enteropathogenic Escherichia coli, enterohaemorrhagic E. coli and the mouse pathogen Citrobacter rodentium. These bacteria attach intimately to intestinal epithelial cells and cause the effacement of the brush border microvilli. Brush border microvilli are finger-like projections on epithelial cells that facilitate nutrient absorption.

Colitis

Inflammation of the colon observed in various disease states

Runting

The birth or development of animals that are smaller than the average size for the species or strain.

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Viswanathan, V., Hodges, K. & Hecht, G. Enteric infection meets intestinal function: how bacterial pathogens cause diarrhoea. Nat Rev Microbiol 7, 110–119 (2009). https://doi.org/10.1038/nrmicro2053

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