The ingestion of germs which take part in the constitution of the intestinal flora is well documented in human history; in fact, as shown in several cave paintings, since the Neolithic Age, the changes in human habits to a lifestyle based on farming and breeding led many populations to the consumption of aliments containing fermented milk. The use of dairy products is also confirmed in the Holy Bible, in the Book of Genesis, and in the discovery of a mummy dating 1615 B.C., which was found in the Chinese desert of Taklamakan with some cheese in its mouth. In ancient Greece, Hippocrates described the nutritional importance of cheese for the athletes. Many years later, according to the legend, the prophet Muhammad donated to the ancestors of the mountaineers of Caucasus Kefir, a drink rich in lactic acid, bacteria, and probiotics which is obtained from the fermentation of milk. Marco Polo reported the use of a comparable drink, “Chemmisi”, during his journey to China. All these historical evidence suggests that the benefits derived from the consumption of probiotics were somehow noted to our ancestors, but the first scientific studies regarding this issue have been conducted by l’ja Il’ič Mečnikov (Charkiv, 05/16/1845 – Paris, 07/16/1916), who speculated a link between the longevity of the Bulgarian shepherds and the large consumption of yogurt, which contributed to the maintenance of balance in the intestinal flora and the inhibition of pathogen bacteria. It is nowadays documented that the benefits on health determined by probiotics consumption can be partly ascribed to their action on the Gut Microbiota, which also plays a major role in gastrointestinal, metabolic and neurodegenerative pathologies, in different ages and environmental conditions.