Editors' ChoiceMICROBIOTA

Good and Bad Bacteria Fight for Iron in the Gut

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Science Translational Medicine  21 Aug 2013:
Vol. 5, Issue 199, pp. 199ec140
DOI: 10.1126/scitranslmed.3007256

Parents with multiple children can attest that there’s always a fight for the last piece of candy or serving of a favorite dessert. Just like human siblings, bacteria fight for coveted nutrients too. Iron—an essential nutrient for most living organisms—is often at the center of fights between humans and pathogenic bacteria and, now, between individual bacteria in the iron-limited environment of the inflamed intestine.

Bacteria in the Enterobacteriaceae family are particularly good at circumventing host factors that limit access to iron during inflammation, and many strains have accumulated iron acquisition proteins in an “arms race” against other bacteria and the host. The pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) uses virulence factors to trigger inflammation and has iron acquisition and metabolic capabilities that give it a growth advantage in the inflamed gut. The probiotic Escherichia coli Nissle 1917 strain does not trigger inflammation, but also has an arsenal of iron acquisition elements that is comparable with or superior to many pathogens.

Deriu and colleagues hypothesized that E. coli Nissle might protect hosts by competing with pathogens for limiting micronutrients such as iron. To test this hypothesis, they evaluated the effect of wild-type E. coli Nissle and E. coli Nissle mutants with deficient iron uptake on S. Typhimurium colonization and mucosal inflammation in acute and chronic mouse models of colitis. Wild-type E. coli Nissle decreased S. Typhimurium colonization regardless of whether it was administered before, during, or after S. Typhimurium inoculation, whereas iron-uptake mutants had no effect on S. Typhimurium levels. Restoration of iron uptake in a mutant E. coli Nissle strain renewed the probiotic’s competitive advantage. Last, in an interesting twist, the authors showed that both wild-type E. coli Nissle and iron-uptake mutant Nissle strains have anti-inflammatory effects on the intestinal mucosa that appeared to be unrelated to their effect on S. Typhimurium.

This study provides compelling evidence that probiotics can benefit their host by engaging in direct competition with harmful bacteria for limiting micronutrients such as iron. At the same time, the study adds to existing research showing that E. coli Nissle and other probiotics likely affect hosts by more than one mechanism. Additional studies are needed to clarify the relative importance of interbacterial competition for micronutrients versus host immune modulation in determining overall probiotic efficacy. It may also be time to reexamine the effect of chronic oral iron supplementation on gut microbial communities and the risk of intestinal disease.

E. Deriu et al., Probiotic bacteria reduce Salmonella Typhimurium intestinal colonization by competing for iron. Cell Host & Microbe 14, 26–37 (2013). [Abstract]

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