Microbes dominate as the most abundant life form on our planet, occupying almost every terrestrial, aquatic and biological ecosystem. We are used to consider the immune system as a defense system developed to fight microorganisms only. However, thanks to the recent developments in the field of metagenomics, our understanding of entire living world has changed. Currently, we believe that entire life on earth depends on mutualistic partnerships (symbiosis) which improve their respective evolutionary fitness. This kind of relationships increases evolutionary fitness of all living beings to the environment. The microbial communities which colonize living organisms in the body or nature are collectively called as the ‘microbiota’. Based on this perspective, a human body can be regarded as a superorganism, as it contains 10-fold higher cells and 100 times more microbe DNA. Any host learns to recognize, restrain and tolerate its commensals, which encounters at birth from the mother and environment. Both the microbiota and the host use tools shaped by millions of years of coevolution to maintain a constant dialogue and a mutualistic conflict relationship. Under normal conditions, the commensal microbiota protects against colonization by pathogens. However, as seen in any relationship, things may go wrong. For instance, small imbalances introduced by the host, particularly in the immune system, or microbes can disturb the dynamic equilibrium between the host and commensals. In such circumstances (dysbiosis), several diseases such inflammatory diseases, obesity, diabetes may develop. Anatomical sites of a host other than the gut are also colonized by unique microbiota. The oral, vaginal, and airway mucosa microbiota play more local roles, such as tissue homeostasis. In this review, after summarizing novel information about the host-microbiota interactions brought by ”-omics”, and I will try to point how to translate these information to treat autoimmune diseases, obesity, diabetes, and perhaps cancer.

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