Élie Metchnikoff first suggested the possibility of colonizing the gut with beneficial flora in the early 20th century.

Probiotics are

  • Francisco Guarner, Gabriela Perdigon, Ge ́rard Corthier, Seppo Salminen, Berthold Koletzko & Lorenzo Morelli, 2005, "Should yoghurt cultures be considered probiotic?," British Journal of Nutrition 93:783–786, DOI 10.1079/BJN20051428, see [8], accessed 11 June 2015.

Further reading

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  2. ^ a b Magdalena Araya, Catherine Stanton, Lorenzo Morelli, Gregor Reid, Maya Pineiro, et al., 2006, "Probiotics in food: health and nutritional properties and guidelines for evaluation," Combined Report of a Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria, Cordoba, Arentina, 1–4 October 2001, and Report of a Joint FAO/WHO Working Group on Drafting Guidelines for the Evaluation of Probiotics in Food, London, Ontario, Canada, 30 April–1 May 2002 [FAO Food and Nutrition paper 85], pp. 1–50, Rome, Italy:World Health Organization (WHO), Food and Agricultural Organization (FAO) [of the United Nations], ISBN 9251055130, see [5], accessed 11 June 2015.
  3. ^ a b Élie [Ilya Ilyich] Metchnikoff, 2004 [1907], The prolongation of life: Optimistic studies, Springer Classics in Longevity and Aging, New York, NY:Springer, ISBN 0826118771, reprint of 1908 English edition by É.M., same title (P. Chalmers Mitchell, Ed.), New York, NY:Putnam, ISBN 0826118763, itself a translation of 1907 French edition by I.I.M., Essais optimistes, Paris:Heinemann, see [6], accessed 11 June 2015.
  4. ^ Starling S (10 November 2011). "EFSA calls for characterisation work as probiotic resubmissions loom". William Reed Business Media. Retrieved 6 January 2015. 
  5. ^ a b Slashinski MJ, McCurdy SA, Achenbaum LS, Whitney SN, McGuire AL; McCurdy; Achenbaum; Whitney; McGuire (2012). Snake-oil," "quack medicine," and "industrially cultured organisms:" biovalue and the commercialization of human microbiome research""". BMC Medical Ethics 13: 28.  
  6. ^ Fuller, R., ed. (1992) Probiotics. The Scieniific Basis. Chapman & Hall, London, U.K
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  8. ^ Hamilton-Miller JM, Gibson GR, Bruck W; Gibson; Bruck (October 2003). "'"Some insights into the derivation and early uses of the word 'probiotic (PDF). Br. J. Nutr. 90 (4): 845.  
  9. ^ Schlundt, Jorgen. "Health and Nutritional Properties of Probiotics in Food including Powder Milk with Live Lactic Acid Bacteria" (PDF). Report of a Joint  
  10. ^ a b c Rijkers GT, Bengmark S, Enck P, Haller D, Herz U, Kalliomaki M, Kudo S, Lenoir-Wijnkoop I, Mercenier A, Myllyluoma E, Rabot S, Rafter J, Szajewska H, Watzl B, Wells J, Wolvers D, Antoine JM; Bengmark; Enck; Haller; Herz; Kalliomaki; Kudo; Lenoir-Wijnkoop; Mercenier; Myllyluoma; Rabot; Rafter; Szajewska; Watzl; Wells; Wolvers; Antoine (2010). "Guidance for substantiating the evidence for beneficial effects of probiotics: current status and recommendations for future research". J. Nutr. 140 (3): 671S–6S.  
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See also

Preliminary research is evaluating the potential physiological effects of multiple probiotic strains, as opposed to a single strain.[114][115] As the human gut may contain several hundred microbial species, one theory indicates that this diverse environment may benefit from consuming multiple probiotic strains, an effect that remains scientifically unconfirmed.

Multiple probiotics

The European Food Safety Authority has so far rejected 260 claims[113] on probiotics in Europe due to insufficient research and thus inconclusive proof. The review did not refute the potential for effectiveness, but rather that a cause-effect relationship had not been sufficiently established in studies to date.

EFSA scientific review of probiotics

Sales of probiotic products have a rising trend from 2010 to 2014, increasing globally by 35% from US$23.1 billion to $31.3 billion.[112] Some regions have increased their use by even more than the average, including Eastern Europe (67%), Asia Pacific (67%), and Latin America (47%), comprising nearly half of probiotics sold globally in 2014.[112] By geographic region, the leading consumers of probiotics in 2014 were Western Europe ($8.3 billion), Asia Pacific ($7 billion), Japan ($5.4 billion), Latin America ($4.8 billion), North America ($3.5 billion), and Eastern Europe ($2.3 billion).[112]

Global consumption

The first commercially sold dairy-based probiotic was Yakult, a fermented milk with added Lactobacillus casei Shirota, in 1935. Since then, many more probiotic foods have come on the market, mostly in the form of dairy products. Recently, nondairy and unfermented probiotics have been produced, including breakfast cereal and snack bars, whereas other probiotic products include kefir, yogurt, kombucha, kimchi, sauerkraut, and other fermented foods and beverages.[110][111]

History and modern products

[109][108] 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.[107] placed a ban on putting the word “probiotic” on the packaging of productsEuropean Commission Because of variability in storage conditions and time before eating, it is difficult to tell exactly how much active culture remains at the time of consumption. Due to these ambiguities, in 2012, the [106] but most companies that give a number report the viable cell count at the date of manufacture, a number probably much higher than existing at the moment of consumption.[105] In 2002, the US [104] CFU/mL cultures per gram (at the time of manufacture).8 The National Yogurt Association gives a Live & Active Cultures seal to yogurt products which contain 10

Labeling ambiguities

Commercial probiotics

Some fermented products are reported to contain similar lactic acid bacteria, including pickled vegetables,[92][93][94][95] fermented bean paste such as tempeh,[96] miso,[97] and doenjang, kefir,[98] buttermilk or karnemelk,[99] kimchi [93][100] pao cai,[95][101] sauerkraut,[102] soy sauce,[103] and zha cai.[95]

For the variety of strains with imputed potential health benefits, see the research section above. Some additional forms of lactic acid bacteria include Lactobacillus bulgaricus, Streptococcus thermophilus, and "Lactobacillus bifidus".

Only preliminary evidence exists for most probiotic health claims. Even for the most studied strains, few have been sufficiently developed in basic and clinical research to warrant approval for health claim status to a regulatory agency such as the Food and Drug Administration or European Food Safety Authority, and to date, no claims have been approved by those two agencies.

Live probiotic cultures are available in fermented dairy products and probiotic fortified foods. However, tablets, capsules, powders, and sachets containing the bacteria in freeze-dried form are also available.


Some experts are skeptical on the efficacy of many strains and believe not all subjects will benefit from the use of probiotics.[91]

One 2009 paper cited a 2007 study in chickens [87] as a support for causally linked probiotic products such as yogurts with obesity trends.[88] However, this is contested as the link to obesity, and other health-related issues with yogurt may link to its dairy and calorie attributes.[89][90]

Probiotics taken orally can be destroyed by the acidic conditions of the stomach. A number of microencapsulation techniques are being developed to address this problem.[86]

Some hospitals have reported treating Lactobacillus septicaemia, which is a potentially fatal disease caused by the consumption of probiotics by people with lowered immune systems or who are already very ill.[84][85]

In a clinical trial aimed at showing the effectiveness of probiotics in reducing childhood allergies, researchers gave 178 children either a probiotic or a placebo for the first six months of their lives. Those given the probiotic were more likely to develop a sensitivity to allergens.[84]

In some situations, such as where the person consuming probiotics is critically ill, probiotics could be harmful. In a therapeutic clinical trial conducted by the Dutch Pancreatitis Study Group, the consumption of a mixture of six probiotic bacteria increased the death rate of patients with predicted severe acute pancreatitis.[83]

Side effects

[82], preventing and alleviating bacterial vaginosis.vaginal flora and rebalance pH, were able to normalize vaginal L. rhamnosus and L. acidophilus producing strains, such as hydrogen peroxide In 2013, researchers found that administration of [81] Probiotic treatment of bacterial vaginosis is the application or ingestion of

Bacterial Vaginosis

Probiotics are commonly given to breast-feeding mothers and their young children to prevent eczema, but some doubt exists over the strength of evidence supporting this practice.[51]


Probiotic treatment has been studied as a means of addressing maladies associated with vitamin deficiency, e.g., of vitamin K,[78] folic acid,[79] and vitamin B12.[80]

Vitamin production

Several clinical studies provide evidence for the potential of probiotics to lower the risk of necrotizing enterocolitis (NEC) and mortality in premature infants. One meta-analysis indicated that probiotics reduce all-cause mortality and risk of having NEC by more than 50% compared with controls.[77]

Necrotizing enterocolitis

No good evidence indicates taking probiotics helps maintain remission from ulcerative colitis.[76]

Probiotics may help people with irritable bowel syndrome, although uncertainty remains around which type of probiotic works best, and around the size of the effect.[75]

Irritable bowel syndrome and colitis

Some strains of LAB may modulate inflammatory and hypersensitivity responses, an observation thought to be at least in part due to the regulation of cytokine function.[68] Clinical studies suggest they can prevent reoccurrences of inflammatory bowel disease in adults,[68] as well as improve milk allergies.[73] How probiotics may influence the immune system remains unclear, but a potential mechanism under research concerns the response of T lymphocytes to proinflammatory stimuli.[74]


Some strains of LAB may affect Helicobacter pylori infections (which may cause peptic ulcers) in adults when used in combination with standard medical treatments, but no standard in medical practice or regulatory approval exists for such treatment.[72]

Helicobacter pylori

Some strains of LAB may affect pathogens by means of competitive inhibition (i.e., by competing for growth) and some evidence suggests they may improve immune function by increasing the number of IgA-producing plasma cells and increasing or improving phagocytosis, as well as increasing the proportion of T lymphocytes and natural killer cells.[68][69] Clinical trials have demonstrated that probiotics may decrease the incidence of respiratory-tract infections[70] and dental caries in children.[71] LAB products might aid in the treatment of acute diarrhea, and possibly affect rotavirus infections in children and travelers' diarrhea in adults,[68][69] but no products are approved for such indications.

Immune function and infections

The consumption of probiotics may effect a modest benefit in helping to control high blood pressure.[67]

Blood pressure

Studies specifically on hyperlipidemic subjects are still needed.

A slightly longer study evaluating the effect of a yogurt with probiotic strains on 29 subjects over six months found no statistically significant differences in total serum cholesterol or LDL values. However, the study did note a significant increase in serum HDL from, 50 to 62 mg/dL (1.28 to 1.6 mmol/L) following treatment. This corresponds to a possible improvement of LDL/HDL ratio.[66]

A meta-analysis that included five double-blind trials examining the short-term (2–8 weeks) effects of a yogurt with probiotic strains on serum cholesterol levels found a minor change of 8.5 mg/dL (0.22 mmol/L) (4% decrease) in total cholesterol concentration, and a decrease of 7.7 mg/dL (0.2 mmol/L) (5% decrease) in serum LDL concentration.[65]

Preliminary human and animal studies have demonstrated the efficacy of some strains of lactic acid bacteria (LAB) for reducing serum cholesterol levels, presumably by breaking down bile in the gut, thus inhibiting its reabsorption (where it enters the blood as cholesterol).[63][64]


Ingestion of certain active strains may help lactose-intolerant individuals tolerate more lactose than they would otherwise have tolerated.[63]

Lactose intolerance

The potential efficacy of probiotic AAD prevention is dependent on the probiotic strain(s) used and on the dosage.[61][62] A Cochrane Collaboration systematic review, in which 16 randomized clinical trials (n=3432 participants) were analyzed, concluded that treatments with less than 5000 million CFUs/day did not show a significant decrease of AAD. However, patients treated with ≥5000 million CFUs/day (including L. rhamnosus and Saccharomyces boulardii) had 60% lower relative risk (95%CI: 44–71%) of experiencing AAD than untreated patients.[55]

Probiotic treatment might reduce the incidence and severity of AAD as indicated in several meta-analyses.[59] For example, treatment with probiotic formulations including L. rhamnosus may reduce the risk of AAD, improve stool consistency during antibiotic therapy, and enhance the immune response after vaccination.[60] However, further documentation of these findings through randomized, double-blind, placebo-controlled trials is required to confirm specific effects and obtain regulatory approval, which currently does not exist.

Some of the best evidence in support of probiotic health benefits is in the treatment of Clostridium difficile.[58]

Antibiotic-associated diarrhea

Some probiotics are suggested as a possible treatment for various forms of gastroenteritis,[52] and a Cochrane Collaboration meta-analysis on the use of probiotics to treat acute infectious diarrhea based on a comprehensive review of medical literature through 2010 (35 relevant studies, >4500 participants) reported that use of any of the various tested probiotic formulations appeared to reduce the duration of diarrhea by a mean of 25 hours (vs. control groups, 95% confidence interval, 16–34 hours), also noting, however, that "the differences between the studies may be related to other unmeasured and unexplored environmental and host factors" and that further research was needed to confirm reported benefits.[53][54]


Probiotics are ineffective in preventing allergies in children, with the possible exception of eczema.[51]


Claims that some lactobacilli may contribute to weight gain in some humans[48][49] remain controversial.[50]

In a 2009 blog post, one expert reasoned that preliminary clinical results exist for some applications, such as treating diarrhea, but wider health benefits claimed by probiotic proponents lack plausibility since the body's "ecosystem" is sufficiently complex that adding a few bacteria is unlikely to have the claimed effect. Accordingly, he reasoned, "the alleged health benefits of probiotics are often an example of spin".[47] Since then, there has been an increase in the body of scientific evidence supporting the use of specific probiotics to improve health. Although the body's complex microbial community is incompletely understood at present, there is strong scientific consensus on the benefits of using of probiotics to address certain medical states or conditions.[13]

Although research does suggest that the relationship between gut flora and humans is a mutualistic relationship,[45] very little evidence supports claims that probiotic dietary supplements have any health benefits.[5] Improved health through gut flora modulation appears to be directly related to long-term dietary changes.[46]

Research into the potential health effects of supplemental probiotics has included the molecular biology and genomics of Lactobacillus in immune function, cancer, and antibiotic-associated diarrhea, travellers' diarrhea, pediatric diarrhea, inflammatory bowel disease, and irritable bowel syndrome.[41] Testing of a probiotic applies to a specific strain under study.[42] The scientific community cautions against extrapolating an effect from a tested strain to an untested strain.[43][44]

Studies are examining whether probiotics affect mechanisms of intestinal inflammation,[37] diarrhea,[38] or urogenital infections.[39] Through 2012, however, in all cases proposed as health claims to the European Food Safety Authority, the scientific evidence remains insufficient to prove a cause-and-effect relationship between consumption of probiotic products and any health benefit.[1][40]

Probiotics are under considerable research, as the concept holds promise for human health and well-being, and corresponding commercial opportunities. Protection of consumers requires health claims to be confirmed with sufficient scientific evidence. Overall scientific demonstration of probiotic effects requires defining a healthy microbiota and interactions between microbiota and host, and the difficulty to characterize probiotic effectiveness in health and disease. Recent developments of high-throughput sequencing technology and the consequent progresses of metagenomics represent a new approach for the future of probiotics research.[36]


In the following decades, intestinal lactic acid bacterial species with alleged health beneficial properties have been introduced as probiotics, including Lactobacillus rhamnosus, Lactobacillus casei, and Lactobacillus johnsonii.[35]

The term "probiotic" originally referred to microorganisms that have effects on other microorganisms.[32] The conception of probiotics involved the notion that substances secreted by one microorganism stimulated the growth of another microorganism. The term was used again[33] to describe tissue extracts which stimulated microbial growth. The term probiotics was taken up by Parker,[34] 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,[14] whose explanation was very close to the definition used today. Fuller 89 described probiotics as a "live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance". He stressed two important facts of probiotics: the viable nature of probiotics and the capacity to help with intestinal balance.

According to Hamilton-Miller et al.,[31] in a letter in which they call for the oldest known citation of the word, the term "probiotics" was first introduced in 1953 by A live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance".[14] Fuller's definition emphasizes the requirement of viability for probiotics and introduces the aspect of a beneficial effect on the host.

In 1920, Rettger and Cheplin reported that Metchnikoff's "Bulgarian Bacillus", later called constipation.

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.[28] 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.

Bifidobacteria were first isolated from a breast-fed infant by Henry Tissier, who also worked at the Pasteur Institute. The isolated bacterium named Bacillus bifidus communis[27] was later renamed to the genus Bifidobacterium. Tissier found that bifidobacteria are dominant in the gut flora of breast-fed babies and he observed clinical benefits from treating diarrhea in infants with bifidobacteria. The claimed effect was bifidobacterial displacement of proteolytic bacteria causing the disease.

It was at that time known that milk fermented with lactic-acid bacteria inhibits 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 found his health benefited. Friends in Paris soon followed his example and physicians began prescribing the sour-milk diet for their patients.[26]

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 flora and to replace harmful microbes with useful microbes.[3] 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 flora, 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.[25]

Probiotics have received renewed attention recently from product manufacturers, research studies, and consumers. The history of probiotics can be traced to the first use of cheese and fermented products, that were well known to the Greeks and Romans who recommended their consumption.[23] The fermentation of dairy foods represents one of the oldest techniques for food preservation.[24]


Finally, probiotics must be supplied in adequate numbers, which may be defined as the number able to trigger the targeted effect on the host. It depends on strain specificity, process, and matrix, as well as the targeted effect. Most of reported benefits demonstrated with the traditional probiotics have been observed after ingestion of a concentration around 107 to 108 probiotic cells per gram, with a serving size around 100 to 200 mg per day.[10]

In Europe, EFSA has adopted a premarket system for safety assessment of microbial species used in food and feed productions, to set priorities for the need of risk assessment. The assessment is made for a selected group of microorganisms, which if favorable, leads to the “Qualified Presumption of Safety” status.[22]

  • Determination of antibiotic resistance patterns
  • Assessment of certain metabolic activities (e.g., D-lactate production, bile salt deconjugation)
  • Assessment of side effects during human studies
  • Epidemiological surveillance of adverse incidents in consumers (after market)
  • If the strain under evaluation belongs to a species that is a known mammalian toxin producer, it must be tested for toxin production. One possible scheme for testing toxin production has been recommended by the EU Scientific Committee on Animal Nutrition[21]
  • If the strain under evaluation belongs to a species with known hemolytic potential, determination of hemolytic activity is required

Probiotics must be safe for their intended use. The 2002 FAO/WHO guidelines recommend that, though bacteria may be generally recognized as safe (GRAS), the safety of the potential probiotic should be assessed by the minimum required tests:

[10] The probiotic candidate must be a taxonomically defined microbe or combination of microbes (

Probiotics have to be alive when administered.[14][15][16] One of the concerns throughout the scientific literature resides in the viability and reproducibility on a large scale of the observed results, as well as the viability and stability during use and storage, and finally the ability to survive in stomach acids and then in the intestinal ecosystem.[17] Probiotics must have undergone controlled evaluation to document health benefits in the target host. Only products containing live organisms shown in reproducible human studies to confer a health benefit can actually claim to be a probiotic.[18][19][20] The correct definition of health benefit, backed with solid scientific evidence, is a strong element for the proper identification and assessment of the effect of a probiotic. This aspect represents a major challenge for scientific and industrial investigations because several difficulties arise, such as variability in the site for probiotic use (oral, vaginal, intestinal) and mode of application.[14]

A group of scientific experts assembled in London, UK, on October 23, 2013, to discuss the scope and appropriate use of the term probiotic. The meeting was motivated by developments in the field since 2001. The panel's conclusions were published in June, 2014.[13]

This effort is accompanied by local governmental and supra-governmental regulatory bodies requirements to better characterize health claims substantiations. [12] The FAO/WHO consultation was also a first effort towards the assessment of probiotics efficacy and resulted in May 2002 in a document named “Guidelines for the Evaluation of Probiotics in Food”.[2] A consensus definition of the term “probiotics”, based on the available information and scientific evidence, was adopted after a joint

The [9] Following this definition, a working group convened by the FAO/WHO in May 2002 issued the “Guidelines for the Evaluation of Probiotics in Food”. This 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 claim.[10][11] The same principles emerged from those groups as the ones expressed in the Guidelines of FAO/WHO in 2002. This definition, although widely adopted, is not acceptable to the European Food Safety Authority because it embeds a health claim which is not measurable.[1]


Some literature gives it a full Greek etymology,[6][7] but the term appears to be a composite of the Latin preposition pro ("for") and the Greek adjective βιωτικός (biotic), the latter deriving from the noun βίος (bios, "life").[8]



  • Etymology 1
  • Definition 2
  • History 3
  • Research 4
    • Allergies 4.1
    • Diarrhea 4.2
      • Antibiotic-associated diarrhea 4.2.1
    • Lactose intolerance 4.3
    • Cholesterol 4.4
    • Blood pressure 4.5
    • Immune function and infections 4.6
    • Helicobacter pylori 4.7
    • Inflammation 4.8
    • Irritable bowel syndrome and colitis 4.9
    • Necrotizing enterocolitis 4.10
    • Vitamin production 4.11
    • Eczema 4.12
    • Bacterial Vaginosis 4.13
  • Side effects 5
  • Strains 6
  • Commercial probiotics 7
    • Labeling ambiguities 7.1
    • History and modern products 7.2
    • Global consumption 7.3
  • EFSA scientific review of probiotics 8
  • Multiple probiotics 9
  • See also 10
  • References 11
  • Further reading 12

Scientific evidence to date has been insufficient to substantiate any antidisease claims or health benefits from consuming probiotics.[1][4][5]

Commonly claimed benefits of probiotics include the decrease of potentially pathogenic gastrointestinal microorganisms, the reduction of gastrointestinal discomfort, the strengthening of the immune system, the improvement of the skin's function, the improvement of bowel regularity, the strengthening of the resistance to cedar pollen allergens, the decrease in body pathogens, the reduction of flatulence and bloating, the protection of DNA, the protection of proteins and lipids from oxidative damage, and the maintaining of individual intestinal microbiota in subjects receiving antibiotic treatment.

Studies on the medical benefits of probiotics have yet to reveal a cause-effect relationship, and their medical effectiveness has yet to be conclusively proven for most of the studies conducted thus far. [1]