The mammalian intestine is colonized by trillions of microorganisms, most of which are bacteria that have co-evolved with the host in a symbiotic relationship. A principal function of the microbiota is to protect the intestine against colonization by exogenous pathogens and potentially harmful indigenous microorganisms via several mechanisms, which include direct competition for limited nutrients and the modulation of host immune responses. Understanding the interplay between the microbiota, pathogens and the host might provide new insights into the pathogenesis of disease, as well as novel avenues for preventing and treating intestinal and systemic disorders. In the intestine, the innate immune system evolved to tolerate commensal microorganisms while maintaining the capacity to trigger host defense responses to invading pathogens. Innate immunity senses the presence of pathogens via pattern recognition receptors (PRRs) like toll like receptors (TLRs) and NLRs receptors. Recent findings suggest that inflammasomes play a critical role in the intricate interplay between the local microbial community and the mucosal immune system by sensing commensal bacteria, regulating microbial ecology, establishing the host defense response that discriminates pathogenic from commensal microbes and preventing the emergence of pathobions. A better understanding of the relationship between PRRs signaling and the intestinal microbiota might provide insight into the complex interaction of the innate immune system with the intestinal environment, and identify new approaches for the treatment of inflammatory bowel disease and gastrointestinal cancer

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