probiotic probiotic probiotics are live microorganisms promoted with claims that they provide health benefits when consumed, generally by improving or restoring the gut microbiota. probiotics are considered generally safe to consume, but may cause bacteria-host interactions and unwanted side effects in rare cases. there is some evidence that probiotics are beneficial for some conditions, but there is little evidence for many of the health benefits claimed for them. not to be confused with prebiotics, food compounds that induce the growth or activity of microorganisms. a bottle of yakult, a probiotic drink containing lactobacillus paracasei the first discovered probiotic was a certain strain of bacillus in bulgarian yoghurt, called lactobacillus bulgaricus. the discovery was made in 1905 by bulgarian physician and microbiologist stamen grigorov. the modern-day theory is generally attributed to russian nobel laureate élie metchnikoff, who postulated around 1907 that yoghurt-consuming bulgarian peasants lived longer. a growing probiotics market has led to the need for stricter requirements for scientific substantiation of putative benefits conferred by microorganisms claimed to be probiotic. although numerous claimed benefits are marketed towards using consumer probiotic products, such as reducing gastrointestinal discomfort, improving immune health, relieving constipation, or avoiding the common cold, such claims are not supported by scientific evidence, and are prohibited as deceptive advertising in the united states by the federal trade commission. as of 2019, numerous applications for approval of health claims by european manufacturers of probiotic dietary supplements have been rejected by the european food safety authority for insufficient evidence of beneficial mechanism or efficacy. definition an october 2001 report by the world health organization (who) defines probiotics as "live microorganisms which when administered in adequate amounts confer a health benefit on the host." following this definition, a working group convened by the food and agriculture organization (fao)/who in may 2002 issued the guidelines for the evaluation of probiotics in food. a consensus definition of the term probiotics, based on available information and scientific evidence, was adopted after the aforementioned joint expert consultation between the fao of the united nations and the who. this effort was accompanied by local governmental and supra-governmental regulatory bodies' requirements to better characterize health claims substantiations. that first global effort was further developed in 2010; two expert groups of academic scientists and industry representatives made recommendations for the evaluation and validation of probiotic health claims. the same principles emerged from those two groups as were expressed in the "guidelines" of fao/who in 2002. this definition, though widely adopted, is not acceptable to the european food safety authority because it embeds a health claim that is not measurable. a group of scientific experts assembled in canada in october 2013 to discuss the scope and appropriate use of the term "probiotic", adjusting the definition to be "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host." in food live probiotic cultures are part of fermented dairy products, other fermented foods, and probiotic-fortified foods. additionally, lactic acid bacteria (labs), which are food fermenting bacteria, have the ability to prevent food spoilage and can improve the nutritive value of the foods they inhabit. also due to its low cost and low energy requirements when processing and preparing foods, acid fermentation, combined with salting, remains one of the most practical methods of preservation of fresh vegetables, cereal gruels, and milk-cereal mixtures. some fermented products that contain lactic acid bacteria include: vegetables such as pickled vegetables, kimchi, pao cai, and sauerkraut; sourdough bread or bread-like products made without wheat or rye flour, amino acid/peptide meat-flavored sauces and pastes produced by fermentation of cereals and legumes; fermented cereal-fish-shrimp mixtures and fermented meats; soy products such as tempeh, miso, and soy sauce; dairy products such as yogurt, kefir, buttermilk; and non-dairy products such as bee pollen. more precisely, sauerkraut contains the bacteria leuconostoc mesenteroides, lactobacillus plantarum, pediococcus pentosaceus, lactobacillus brevis, leuconostoc citreum, leuconostoc argentinum, lactobacillus paraplantarum, lactobacillus coryniformis, and weissella spp. kimchi contains the bacteria leuconostoc spp., weissella spp., and lactobacillus spp. pao cai contains l. pentosus, l. plantarum , leuconostoc mesenteroides , l. brevis, l. lactis, and l. fermentum. a list of many other bacteria found in several asian fermented fruits and vegetables also is available. kefir contains lactobacillus acidophilus, bifidobacterium bifidum, streptococcus thermophilus, lactobacillus delbrueckii subsp. bulgaricus, lactobacillus helveticus, lactobacillus kefiranofaciens, lactococcus lactis, and leuconostoc species. buttermilk contains either lactococcus lactis or l. bulgaricus. other acidic bacteria, said to be probiotic, also can be found in kombucha. this drink contains gluconacetobacter xylinus. it also contains zygosaccharomyces sp., acetobacter pasteurianus, acetobacter aceti, and gluconobacter oxydans. side effects the manipulation of the gut microbiota is complex and may cause bacteria-host interactions. though probiotics are considered safe, some have concerns about their safety in certain cases. some people, such as those with immunodeficiency, short bowel syndrome, central venous catheters, and cardiac valve disease, and premature infants, may be at higher risk for adverse events. in severely ill people with inflammatory bowel disease, a risk exists for the passage of viable bacteria from the gastrointestinal tract to the internal organs (bacterial translocation) as a consequence of bacteremia, which can cause adverse health consequences. rarely, consumption of probiotics by children with lowered immune system function or who are already critically ill may result in bacteremia or fungemia (i.e., bacteria or fungi in the blood), which can lead to sepsis, a potentially fatal disease. lactobacillus species have been suggested to contribute to obesity in humans, but no evidence of this relationship has been found. consumption in 2015, the global retail market value for probiotics was us$41 billion, including sales of probiotic supplements, fermented milk products, and yogurt, which alone accounted for 75% of total consumption. innovation in probiotic products in 2015 was mainly from supplements, which produced us$4 billion and was projected to grow 37% globally by 2020. consumption of yogurt products in china has increased by 20% per year since 2014. regulation as of 2019, the european food safety authority has rejected all petitions by commercial manufacturers for health claims on probiotic products in europe due to insufficient evidence for a cause-and-effect mechanism for benefit, thus inconclusive proof of effectiveness. the european commission placed a ban on putting the word "probiotic" on the packaging of products because such labeling misleads consumers to believe a health benefit is provided by the product when no scientific proof exists to demonstrate that health effect. in the united states, the food and drug administration (fda) and federal trade commission (ftc) have issued warning letters and imposed punishment on various manufacturers of probiotic products whose labels claim to treat a disease or condition. food product labeling requires language approved by the fda, so probiotic manufacturers have received warning letters for making disease or treatment claims. the ftc has taken punitive actions, including a us$21 million fine coordinated by 39 different state governments against a major probiotic manufacturer for deceptive advertising and exaggerated claims of health benefits for yogurt and probiotic dairy drink. yogurt labeling the national yogurt association (nya) of the united states gives a "live & active cultures seal" to refrigerated yogurt products that contain 100 million cells per gram, or frozen yogurt products that contain 10 million cells per gram at the time of manufacture. in 2002, the fda and who recommended that "the minimum viable numbers of each probiotic strain at the end of the shelf-life" be reported on labeling, but most companies that give a number report the viable cell count at the date of manufacture, a number that could be much higher than that which exists at consumption. because of the variability in storage conditions and time before eating, exactly how many active culture cells remain at the time of consumption is difficult to determine. the survival of probiotics was strongly dependent on the storage temperature and remarkable viability loss occurred in room temperature compared to refrigerated storage. history probiotics have received renewed attention in the 21st century from product manufacturers, research studies, and consumers. their history can be traced to the first use of cheese and fermented products, which were well-known to the greeks and romans who recommended their consumption. the fermentation of dairy foods represents one of the oldest techniques for food preservation. élie metchnikoff first suggested the possibility of colonizing the gut with beneficial bacteria in the early 20th century. the original modern hypothesis of the positive role played by certain bacteria was first introduced by russian scientist and nobel laureate élie metchnikoff, who in 1907 suggested that it would be possible to modify the gut microbiota and to replace harmful microbes with useful microbes. metchnikoff, at that time a professor at the pasteur institute in paris, proposed the hypothesis that the aging process results from the activity of putrefactive (proteolytic) microbes producing toxic substances in the large bowel. proteolytic bacteria such as clostridia, which are part of the normal gut microbiota, produce toxic substances including phenols, indols, and ammonia from the digestion of proteins. according to metchnikoff, these compounds were responsible for what he called "intestinal autointoxication", which would cause the physical changes associated with old age. at that time, milk fermented with lactobacillales were known to inhibit the growth of proteolytic bacteria because of the low ph produced by the fermentation of lactose. metchnikoff had also observed that certain rural populations in europe, for example in bulgaria and the russian steppes, who lived largely on milk fermented by lactic-acid bacteria, were exceptionally long-lived. based on these observations, metchnikoff proposed that consumption of fermented milk would "seed" the intestine with harmless lactic-acid bacteria and decrease the intestinal ph, and that this would suppress the growth of proteolytic bacteria. metchnikoff himself introduced in his diet sour milk fermented with the bacteria he called "bulgarian bacillus" and believed his health benefited. friends in paris soon followed his example and physicians began prescribing the sour-milk diet for their patients. bifidobacteria was first isolated from a breastfed infant by henry tissier, who also worked at the pasteur institute. the isolated bacterium named bacillus bifidus communis was later renamed to the genus bifidobacterium. tissier found that bifidobacteria are dominant in the gut microbiota of breast-fed babies and he observed clinical benefits from treating infant diarrhea with bifidobacteria. during an outbreak of shigellosis in 1917, german professor alfred nissle isolated a strain of escherichia coli from the feces of a soldier who was not affected by the disease. methods of treating infectious diseases were needed at that time when antibiotics were not yet available, and nissle used the e. coli nissle 1917 strain in acute gastrointestinal infectious salmonellosis and shigellosis. in 1920, rettger and cheplin reported that metchnikoff's "bulgarian bacillus", later called lactobacillus delbrueckii subsp. bulgaricus, could not live in the human intestine. they conducted experiments involving rats and humans volunteers, feeding them with lactobacillus acidophilus. they observed the disappearance of the pathogenic protist balantidium coli as well as of other gas-producing bacteria. rettger further explored the possibilities of l. acidophilus, and reasoned that bacteria originating from the gut were more likely to produce the desired effect in this environment. in 1935, certain strains of l. acidophilus were found very active when implanted in the human digestive tract. contrasting antibiotics, probiotics were defined as microbially derived factors that stimulate the growth of other microorganisms. in 1989, roy fuller suggested a definition of probiotics that have been widely used: "a live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance." fuller's definition emphasizes the requirement of viability for probiotics and introduces the aspect of a beneficial effect on the host. the term "probiotic" originally referred to microorganisms that have effects on other microorganisms. the concept of probiotics involved the notion that substances secreted by one microorganism stimulated the growth of another microorganism. the term was used again to describe tissue extracts that stimulated microbial growth. the term probiotics was taken up by parker, who defined the concept as, "organisms and substances that have a beneficial effect on the host animal by contributing to its intestinal microbial balance." later, the definition was greatly improved by fuller, whose explanation was very close to the definition used today. fuller described probiotics as a "live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance." he stressed two important claims for probiotics: the viable nature of probiotics