Microbiota and innate immunity in intestinal inflammation and neoplasia

Abstract

This review focuses on recent advances and novel insights into the mechanistic events that may link commensal microbiota and host innate immunity in the pathophysiology of intestinal inflammation and neoplasia. Unanswered questions are discussed and future perspectives in the field are highlighted. Commensal microbiota, host innate immunity, and genetics form a multidimensional network that controls homeostasis of the mucosal barrier in the intestine. Large-scale sequencing projects have begun to catalog the healthy human microbiome. Converging evidence suggests that alterations in the regulation of the complex host environment [e.g., dysbiosis and overgrowth of select commensal bacterial species, dietary factors, copresence of facultative pathogens (including viruses), and changes in mucus characteristics] may trigger aberrant innate immune signaling, thereby contributing to the development of intestinal inflammation and associated colon cancer in the susceptible individual. Genetically determined innate immune malfunction may create an inflammatory environment that promotes tumor progression (such as the TLR4-D299G mutation). The next challenging steps to be taken are to decipher changes in the human microbiome (and virome) during well defined diseased states, and relate them to intestinal mucosal immune functions and host genotypes.