One of the clearest functions of the gut microbiota in humans is resistance to colonization by enteric bacterial pathogens. Reconstitution of the microbiota offers an exciting therapeutic approach, but great challenges must be overcome.

Main Text

We are all covered by and filled with bacteria. The first decade of sequence-based exploration of the human microbiome has established the importance of this dense and diverse ecosystem that we all carry. Entire fields of biology, such as physiology, immunology, and behavior, are in the process of realigning to account for the effects of the microbiota within their existing intellectual frameworks. In enteric infectious diseases, where the microbiota was generally believed to serve as a physical barrier to pathogens, our understanding of microbiota-mediated resistance has evolved considerably. It is now clear that the microbiota are active participants in preventing and sometimes in driving disease, depending on the state of the system. Work in the field has been driven by the idea that, if beneficial missing microbes are added back to the intestine, it may force out the offending microbes, rebalance the system, and prevent disease. Targeted approaches to rehabilitating the intestinal ecosystem, with fully defined indications, therapeutics, and diagnostics, may still be years away, but the remarkable success of early trials treating recurrent Clostridium difficile infection by reconstitution of the gut microbiota is cause for measured but realistic hope. Here, we will survey the known functions of the gut microbiota in defense against enteric infectious diseases with a focus on C. difficile, and we will address some of the major challenges facing those who hope to target the gut microbiota for therapy.

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