Editors' ChoiceENTERIC INFECTIONS

Gut Pathogens: Freeloading Dinner Guests?

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Science Translational Medicine  25 Sep 2013:
Vol. 5, Issue 204, pp. 204ec159
DOI: 10.1126/scitranslmed.3007630

The human intestine is colonized by a complex community of microbes (the microbiota) that feed on its nutrients and ultimately protect it from infection by harmful bacteria. Antibiotic treatment, which alters the intestinal microbiota, is a main risk factor for development of intestinal infections due to these harmful bacteria. Ng and colleagues recently used a mouse model to explore how antibiotics alter the intestinal environment to allow harmful bacteria to establish infection.

The authors colonized “germ-free” mice (those without intestinal microbes) with a single strain of Bacteroides, a species of bacteria that normally colonizes the human intestine. They then infected these mice with two harmful bacterial pathogens that can cause severe intestinal infections, Salmonella enterica serovar Typhimurium (S. typhimurium) and C. difficile. Using a series of experiments comparing gene expression and growth of the harmful bacteria in colonized versus “germ-free” mice, the authors found that the harmful bacteria used the sugar sialic acid as an energy source for growth. This sugar is released from the gut by Bacteroides and is used by some intestinal microbes for energy. When the harmful bacteria were mutated so that they could not use sialic acid, or Bacteroides was mutated so that it could not release sialic acid, the harmful bacteria did not grow well. Last, when mice with normal intestinal microbiota were given antibiotics, gut sialic acid levels spiked within 1 day, which is coincident with harmful bacterial growth. Mutant S. typhimurium and C. difficile strains that could not use sialic acid did not grow well in antibiotic-treated mice, confirming the importance of sialic acid utilization for growth of harmful bacteria after antibiotic treatment.

This study demonstrates that intestinal microbes—the good bacteria—are able to prevent infections by certain harmful bacteria by competing with them for carbohydrate nutrients. After antibiotic treatment, harmful bacteria take advantage of gut nutrients released by the good bacteria in order to establish infection. By providing a mechanism by which antibiotics have this effect, this work may pave the way for new strategies to reduce gut sialic acid and prevent antibiotic-associated enteric infections.

K. M. Ng et al., Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens. Nature, published online 1 September 2013 (10.1038/nature12503). [Abstract]

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