Gastrointestinal (GI) tract seems to be the organ in the body; however, its lumen is external environment because opening to the external environment from mouth and anus. Moreover, it cannot be thought of the place where there are more than 1,000 species and 100-trillion numbers of microorganisms as an internal environment. Many multicellular animals including humans’ separates between internal environment and external environment by special tissues called epithelia. Barrier functions of epithelia prevent invading of luminal antigens, harmful substances, and microorganisms, etc, so that all the other cells excepting epithelial cells can leave from expose of them. However, on the ground of function of nutrient ingestion, the structure of the epithelium lining the lumen of the GI tract can strengthen not so much and consists of only one-layer of epithelial cells called simple columnar epithelium, different from the epidermis consisting of a strong barrier called stratified squamous epithelia. Therefore, the GI tract must have special host-defense functions making up for the weak barrier simultaneously to conduct the contradictory functions of nutrient ingestion and prevention from invasion of harmful substances and microorganisms.