Gut microbiota are permanent residents of humans with the highest concentrations being found in human colon. Humans get the first contact with bacteria at delivery, and microbiota are subject of permanent change during the life. The individual microbiota pattern is highly variable and varying environmental conditions, e.g., diets, antigen exposure, infections, or medication, as well as genetics, age, or hygiene factors, strongly influence the bacterial community. A fine interaction between the host and microbiota determines the outcome of health or disease. The gut immune system is constantly challenged to distinguish between commensal non-invasive bacteria and potential pathogens. Goblet cells produce mucins that prevent most gut bacteria from penetrating through intestinal epithelial barrier, and Paneth cells are the main supplier of anti-microbial defensins. Gut epithelial and immune cells recognize bacteria via surface markers and they initiate an adequate immune answer. A dysbiosis is noticed in several diseases, but the crucial role in pathogenesis has to be proven. Prebiotics or probiotics are discussed as valuable tools to preserve or restore a healthy gut community.