The word probiotic (from the latin pro and the greek βιοσ literally meaning “for life”) was introduced by the German scientist Werner Kollath in 1953 to designate “active substances that are essential for a healthy development of life.” In 1965, this term was used by Lilly and Stillwell in a different context to represent “substances secreted by one organism which stimulate the growth of another.” More specifically, Fuller in 1992 defined probiotics as “a live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance.”1
The modern history of probiotics starts at the beginning of 1900s with the pioneering studies of the future Nobel laureate Elie Metchnikoff, a Russian scientist working at the Pasteur Institute in Paris. Louis Pasteur identified the microorganisms responsible for the process of fermentation, whereas Metchnikoff tried first to find out the possible effect of these microbes on human health. He associated the enhanced longevity of Bulgarian rural people to the regular consumption of fermented dairy products such as yogurt. He linked this to the Bulgarian bacillus which was discovered by a 27-year-old Bulgarian physician Stamen Grigorov, and he later suggested that lactobacilli might counteract the putrefactive effects of gastrointestinal metabolism that contributed to illness and aging. Hippocrates, moreover, declared, 2000 years earlier, that “death sits in the bowels,” and that “bad digestion is the root of all evil.” Metchnikoff also claimed that toxins originated from bacterial putrefaction in the large intestine, and from there released into the circulation are the cause of aging. He termed these bacteria as putrefying bacteria, which is now recognized as proteolytic clostridia. Metchnikoff also stated that “the dependence of the intestinal microbes on the food makes it possible to adopt measures to modify the flora in our bodies and to replace the harmful microbes by useful microbes.” This sentence describes in a clear way the “probiotic concept.” Metchnikoff considered the lactobacilli as probiotics (“pro-bios,” conducive to life of the host as opposed to antibiotics); probiotics could have a positive influence on health and prevent aging. The scientific hypothesis of Metchnikoff favored the creation and development of the dairy industry in France, the first in Europe, thanks to the use of a fermented milk obtained from Bacillus bulgaricus. In 20132 an expert consensus document had been published on the scope and appropriate use of the term probiotic: live microorganisms which when administered in adequate amounts confer a health benefit on the host. Modern technology has also selected those strains producing a fermented milk with good organoleptic and nutritional qualities, more than other strains do. Yogurt and other foods made from fermented milk can be considered the first functional foods, according to a consensus document.3
Nevertheless, the history of probiotics is as old as the human history,4 as it is closely related to the use of fermented food. It should be hypothesized that as farming started to replace hunting and gathering around 10,000 years ago, man began to produce fermented food and beverages. In fact during the neolitic period of the age of the stone, the domestication of animals occurred. Sumerians were the first people to settle and to develop animal husbandry. In the ancient Indian Ayurvedic texts consumption of milk and dairy products is associated with a long and healthy life. Nevertheless, the first pictorial evidence on the practice of milking (whose technique has remained unchanged until the early 1900s when they invented the first milking machines) emerged during excavations of the city of Ur—the ancient center of Mesopotamia, birthplace of Abraham—and dated back to 3100 bc. A man sitting on a stool is depicted; he squeezes the long nipples of a cow and collects milk in a bucket. About 9 centuries earlier, a farmer cut open his accounts in Sumerian cuneiform alphabet on clay tablets that are now preserved in the State Museum of the Middle East Berlin. He posted excellent returns in milk, butter, and cheese from his rich herd of cattle. Are roughly contemporary both the seal exposed to the Museum of Natural History in Chicago in which a goat that, under the watchful eye of a goddess of fertility, offers her own milk to the pastor, and a polychrome Sumerian fresco by 2500 bc, kept in the museum of Baghdad; it shows large cows like Aurochs with their young; near them, large jars collect milk, while the cream poured into a churn from a orciolino becomes butter. In the so-called “frieze of the dairy” Sumerian priests carry the milking. The origin of fermented milk goes back to the ancient Egyptians and Phoenicians and Eastern cultures. The ancient Oriental peoples, white, Phrygian, Sarmatian, and Macedonians nomadic shepherds kept milk from cows, sheep, goat, horse, and camel in bottles made from the skin or from the stomach of the same animal where milk came into contact with the bacteria, probably the ancestors of the acidophilus and bulgaricus that today have become so famous. Legend tells that one of these shepherd travelling in the hot sun of Turkish desert forgot milk in a goatskin bag for some time and whereupon found it transformed into a thick, creamy, and tasty custard. This new product was referred to as “yogurt.” Whatever the origin, the beneficial health properties and therapeutic use of yogurt and other fermented milks has been known since time immemorial, long before the existence of bacteria was recognized. For the Turks yogurt was the elixir of life. They believed that yogurt might give physical and inner well-being and prolong lifespan.
Yogurt was easily carried by nomads as it is easily storable and nonperishable; thus fermentation, from latin fervere (to boil), is the older form of food preservation as well as a way to increase taste and digestibility of food.
Nobody knows exactly when man began to get fermented food and probably serendipitous contaminations in favorable environments played a major role. The introduction of dairying was a major innovation in prehistoric agriculture, with milk and fermented product of milk such as cheese and yogurt being rapidly introduced as major components of diets of our ancestors.
Nearly every civilization has developed food fermentation of some type. Archeologists have found evidence for the production of a fermented beverage as early as 7000 bc in the Neolithic village of Jiahu in China and 5000 bc in Mesopotamia. In Asia fermented beverages were mainly made from rice, whereas in ancient Egypt and Mesopotamia were made from fruits (wine), from honey (mead), and from malted cereals (beer) (Table 1).
Iconographic and written evidence from 3000 and 2000 bc indicated that Hindu, Egyptians, Greeks, and Romans used fermented milk products, although its origins probably lie much earlier. Indeed they are mentioned in the early sacred books of Hinduism and in the Holy Bible. In the Bible one of the first references is found in Genesis (18: 1-8) where it is said that Abraham offered to the Lord “veal, buns and sour milk.”
According to legend the Prophet Muhammad gave as a gift the first kefir grains to the ancestors of the mountaineers of Caucasus. Kefir is a drink rich in lactic acid bacteria and probiotics from the fermentation of milk.
In Odyssey by Homer the Cyclops Polyphemus prepares the cheese in the cave.
Plinio in his Naturalis Historia says he tasted a thick and deliciously acid milk for which the barbarians were going crazy. He recommended the use of fermented milk for treating gastrointestinal infections.
The concept of functional food can be traced back even to Hippocrates IV century who wrote: “let the food be your medicine and medicine be your food.” He supported the nutritional value of cheese which was given to Olympic athletes.
Marco Polo reported a comparable drink named Chemmisi in China.
Tibetan nomads used fermented yak milk.
The cheese was neglected in the high middle age and recovered in the late middle age when it was mostly produced in monasteries.
In the XVI century, Suleiman the Magnificent sent a physician from his Turkish court to prescribe yogurt and successfully treat the severe diarrhea suffered by Francis I of France.
The health properties of these dairy products were a part of folklore until the concept of probiotics emerged, and the study of fermented milks and yogurt containing probiotic bacteria has become more systematic. Functional foods have thus developed as a food, or food ingredient, with positive effects on host health and/or well-being beyond their nutritional value, and fermented milk with probiotic bacteria has again become the prominent representative of this new category of food. In the words of Hippocrates: “Let food be your medicine and medicine be your food.” Yet, according to ancient physicians, animal milk is not appropriate food for man: Hippocrates and Galeno, while recognizing the high nutritional value, advised only for medicinal use, emphasizing the many dangers in terms of food. These beliefs perhaps were based even on grounds of environment and climate: Mediterranean climate was not fit for consumption of a delicate product such as milk, at a time when instruments were missing for the hygienic control of the product and effective techniques for its conservation. The Romans were the first to use milk of cattle, which had been considered harmful, instead of milk of sheep. Marco Terenzio Varrone classified the different types of cheese.
The oldest cheese in the world was found on a mummy of 1615 bc in the Chinese desert of Taklamakan; it was probably part of the food left in the grave.
In past centuries in Italy, at the time of threshing, women were used to bring workers a drink made with water, milk, and lemon which produced milk coagulation. It was believed that this preparation would prevent intestinal infections in people who struggled hard in the heat and dust. This custom continues even in our times in memory of the past.
In the 17th century in some Italian regions there was also a belief that other beverages prevented intestinal infection. We became aware of an ancient custom after having found an old cup named gamelio. Gamelio was a wedding gift (Fig. 1). It was used for washing after intercourse. The derived liquid washing was then drunk. This practice could represent a kind of germ planting.
A special form of probiotic therapy is fecal bacteriotherapy or stool transplant or fecal microbiota transplantation in which a bolus of washed suspended feces obtained from a healthy donor is directly infused into a patient’s colon either as an enema or via endoscopy. Its use as therapy in humans was first reported by Eiseman et al,5 a team of surgeons from Colorado, who successfully treated 4 patients with fulminant pseudomembranous enterocolitis in the late 1950s. However, the first known account of fecal transplantation dates to a fourth-century Chinese handbook by the physician Ge Hong, who prescribed a human fecal suspension by mouth as a remedy for food poisoning or severe diarrhea. Later in the Ming dynasty, the influential XVI-century Chinese physician used “yellow soup,” “golden syrup,” and other remedies containing fresh, dried, or fermented stool to treat abdominal diseases.
Remarkably, the concept of transferring intestinal samples in veterinary practice was in use around the same time in Europe where the Italian anatomist Fabricius Aquapendente (1533-1619) described the practice known as “transfaunation” consisting of inoculating rumen fluid presumably into cows that had lost the capacity to ruminate. It is still used to treat ruminating animals, like cows and sheep, by feeding rumen of a healthy animal to another individual of the same species to colonize its gastrointestinal tract with normal bacteria. In addition, in the second part of last century, the fecal transplantation was extended to avian species to protect the chicken from infections, notably from Salmonella spp.
During World War II, German soldiers in Africa, upon observation of the native Bedouins, used fresh camel feces as treatment for dysentery. The dung consumption only worked if fresh because the active “ingredient” was later identified as Bacillus subtilis.
A recent editorial paper reports: fecal microbiota transplantation—an old therapy comes of age.6 After the first report in the literature by Eiseman, fecal transplant has increased in popularity due to its efficacy and ease of use for the treatment of patients with Clostridium difficile infections. In January 2013, the New England Journal of Medicine7 published the results of the first randomized controlled trial involving fecal transplant, comparing the therapy to treatment with vancomycin for patients with recurrent disease. The trial was ended early as it would be unethical to continue: less than one-third of the patients given vancomycin recovered, compared with 94% of those who underwent fecal transplants, the vast majority after a single treatment.
Historical perspectives provide a very meaningful context to the current state of the contemporary research on the intestinal microbiota and its manipulation to treat human diseases.8–10 Today the interaction of the gut flora with its host and mutual regulation has become one of the important topics of biomedical research even though its relevance and exact role require much more research.
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2. Hill C, Guarner F, Reid G, et al. The International Scientific Association for Probiotics and Prebiotics consensus on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014;11:506–514.
3. Diplock AT, Aggett PJ, Ashwell M, et al. Scientific concepts of functional foods in Europe consensus document. Br J Nutr. 1999;81:S1–S27.
4. Ozen M, Dinleyici EC. The history of probiotics: the untold story. Benef Microbes. 2015;6:159–165.
5. Eiseman B, Silen W, Bascom GS, et al. Fecal enema as an adjunct in the treatment of pseudomembranous enterocolitis. Surgery. 1958;44:854–859.
6. Kelly CP. Fecal microbiota transplantation—an old therapy comes of age. N Engl J Med. 2013;368:474–475.
7. Van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile
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9. Zhang F, Luo W, Shi Y, et al. Should we standardize the 1,700-year-old fecal microbiota transplantation? Am J Gastroenterol. 2012;107:1755–1756.
10. Cammarota G, Masucci L, Gasbarrini A, et al. Randomised clinical trial: faecal microbiota transplantation by colonoscopy vs. vancomycin for the treatment of recurrent Clostridium difficile
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