Probiotic

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Probiotics are defined as microorganisms that are believed to provide health benefits when consumed.[1][2] The term probiotic is currently used to name ingested microorganisms associated with benefits for humans and animals.[3] The term came into more common use after 1980. The introduction of the concept (but not the term) is generally attributed to Nobel laureate Élie Metchnikoff, who postulated that yogurt-consuming Bulgarian peasants lived longer lives because of this custom.[4] He suggested in 1907 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".[5] A significant expansion of the potential market for probiotics has led to higher requirements for scientific substantiation of putative benefits conferred by the microorganisms.[2]

Although there are numerous claimed benefits of using commercial probiotics, such as reducing gastrointestinal discomfort, improving immune health, relieving constipation, or avoiding the common cold, such claims are not backed by scientific evidence[2][6][7] and are prevented as deceptive advertisements in the United States by the Federal Trade Commission.[8]

Probiotics are considered to be generally safe, but they may cause bacteria-host interactions and unwanted side effects in rare cases.[9][10][11]

Etymology[edit]

Some literature gives the word a full Greek etymology,[12][13] but it appears to be a composite of the Latin preposition pro ("for") and the Greek adjective βιωτικός (biōtikos), "fit for life, lively",[14] the latter deriving from the noun βίος (bios, "life").[15] The term contrasts etymologically with the term antibiotic.

Definition[edit]

The World Health Organization's (WHO) 2001 definition of probiotics is "live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host".[16] 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 claims.[17][18] 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.[2]

A consensus definition of the term “probiotics”, based on the available information and scientific evidence, was adopted after a joint Food and Agricultural Organization (FAO) of the United Nations and World Health Organization (WHO) expert consultation. In October 2001 this expert consultation defined probiotics as: “live micro-organisms which, when administered in adequate amounts, confer a health benefit on the host”.[3] 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".[19] This effort was accompanied by local governmental and supra-governmental regulatory bodies requirements to better characterize health claims substantiations.

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.[1]

Probiotics have to be alive when administered.[20][21][22] 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.[2] 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.[2][23][24] 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.[20]

The probiotic candidate must be a taxonomically defined microbe or combination of microbes (genus, species, and strain level). It is commonly admitted that most effects of probiotics are strain-specific and cannot be extended to other probiotics of the same genus or species.[21] This calls for a precise identification of the strain, i.e. genotypic and phenotypic characterization of the tested microorganism.[17]

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:[25]

  • 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[26]
  • If the strain under evaluation belongs to a species with known hemolytic potential, determination of hemolytic activity is required

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.[27]

Finally, probiotics must be supplied in adequate numbers, which may be defined as the number able to trigger the targeted effect on the host.[citation needed] 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.[17][not in citation given]

History[edit]

Probiotics have received renewed attention in the 21st century 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.[28] The fermentation of dairy foods represents one of the oldest techniques for food preservation.[29]

Élie Metchnikoff first suggested the possibility of colonizing the gut with beneficial flora 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 flora and to replace harmful microbes with useful microbes.[5] 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.[30]

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 believed his health benefited. Friends in Paris soon followed his example and physicians began prescribing the sour-milk diet for their patients.[31]

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[32] 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.[citation needed]

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.[33] 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.[citation needed]

In 1920, Rettger and Cheplin reported that Metchnikoff's "Bulgarian Bacillus", later called Lactobacillus delbrueckii subsp. bulgaricus, could not live in the human intestine.[34] They conducted experiments involving rats and humans volunteers, feeding them with Lactobacillus acidophilus. They observed changes in composition of fecal microbiota, which they described as "transformation of the intestinal flora".[34] 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 to be very active when implanted in the human digestive tract.[35] Trials were carried out using this organism, and encouraging results were obtained, especially in the relief of chronic constipation.[citation needed]

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 has been widely used: "A live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance".[20] 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.[36] The conception of probiotics involved the notion that substances secreted by one microorganism stimulated the growth of another microorganism. The term was used again[37] to describe tissue extracts which stimulated microbial growth. The term probiotics was taken up by Parker,[38] 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,[20] 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 facts of probiotics: the viable nature of probiotics and the capacity to help with intestinal balance.

In the following decades, intestinal lactic acid bacterial species with alleged health beneficial properties were introduced as probiotics, including Lactobacillus rhamnosus, Lactobacillus casei, and Lactobacillus johnsonii.[39]

Scientific reviews and regulatory actions[edit]

The European Food Safety Authority has rejected all petitions by commercial manufacturers for health claims on probiotic products in Europe due to insufficient research, and thus inconclusive proof of effectiveness.[2][40] Occurring over many years, the scientific reviews established that a cause-and-effect relationship had not been sufficiently proven in the products submitted.[40]

In the United States, where food product labeling requires language approval by the FDA, probiotic manufacturers have received warning letters of impending legal actions for using exaggerated claims of health benefits not supported by clinical evidence of efficacy.[7][41] The Federal Trade Commission has taken punitive actions, including a US$21 million fine coordinated across 39 state governments against a major probiotic manufacturer, for deceptive advertising and exaggerated claims of health benefits for a yogurt and probiotic dairy drink.[8]

Research[edit]

Four different mechanisms under research by which probiotics may defend against pathogens in the intestine. Probiotics may compete against pathogens for the same essential nutrients, leaving less available for the pathogen to utilize (A). They may bind to adhesion sites, preventing pathogen attachment by reducing the surface area available for pathogen colonization (B). Signaling of immune cells by probiotics may result in the secretion of cytokines, targeting the pathogen for destruction (C). Finally, probiotics may attack pathogenic organisms by releasing bacteriocins, killing them directly (D).[42]

Probiotics have been the subject of research to see whether the health claims made for them have any supporting evidence.[2][43] Scientific demonstration of probiotic effects on health and disease first requires a definition of healthy microbiota as well as an understanding of the complex interactions between microbiota and host, which are not yet well-understood. Recent developments of high-throughput sequencing technology and the consequent progresses of metagenomics represent a new approach for the future of probiotics research.[44]

Studies are examining whether probiotics affect mechanisms of intestinal inflammation,[45] diarrhea,[46] or urogenital infections.[47] As of 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.[2][40]

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.[48] Testing of a probiotic applies to a specific strain under study.[49] The scientific community cautions against extrapolating an effect from a tested strain to an untested strain.[50][51]

Although research does suggest that the relationship between gut flora and humans is a mutualistic relationship,[52] very little evidence supports claims that probiotic dietary supplements have any health benefits.[6] Improved health through gut flora modulation appears to be directly related to long-term dietary changes.[53]

Claims that some lactobacilli may contribute to weight gain in some humans[54][55] remain controversial.[56]

According to the National Center for Complementary and Integrative Health, "Although some probiotics have shown promise in research studies, strong scientific evidence to support specific uses of probiotics for most health conditions is lacking." [57]

Allergies[edit]

Probiotics are ineffective in preventing allergies in children, with the possible exception of eczema.[58]

Antibiotic-associated diarrhea (AAD)[edit]

Antibiotics are a common treatment for children, and 20% of antibiotic-treated children develop diarrhea. Antibiotic-associated diarrhea results from an imbalance in the colonic microbiota caused by antibiotic therapy. Microbiota alteration changes carbohydrate metabolism, with decreased short-chain fatty acid absorption and osmotic diarrhea as a result. The Cochrane review (2015) concluded that the evidence gathered suggested a protective effect of some probiotics in this condition in children.[59] In adults, some probiotics showed a beneficial role in reducing the occurrence of AAD.[60]

Probiotic treatment might reduce the incidence and severity of AAD as indicated in several meta-analyses.[61][62][63] 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.[64]

The potential efficacy of probiotic AAD prevention is dependent on the probiotic strain(s) used and on the dosage.[65][66] The Cochrane review (2015) recommends for children Lactobacillus rhamnosus or Saccharomyces boulardii at 5 to 40 billion colony forming units/day, given the modest number need to treat and the likelihood that adverse events are very rare.[59] The same review states that probiotic use should be avoided in pediatric populations at risk for adverse events, for example severely debilitated or immuno-compromised children.

Bacterial vaginosis[edit]

Probiotic treatment of bacterial vaginosis is the application or ingestion of bacterial species found in the healthy vagina to cure the infection of bacteria causing bacterial vaginosis. This treatment is based on the observation that 70% of healthy females have a group of bacteria in the genus Lactobacillus that dominate the population of organisms in the vagina. Currently, the success of such treatment has been mixed since the use of probiotics to restore healthy populations of Lactobacillus has not been standardized. Often, standard antibiotic treatment is used at the same time that probiotics are being tested. In addition, some groups of women respond to treatment based upon ethnicity, age, number of sexual partners, pregnancy, and the pathogens causing bacterial vaginosis.[67] In 2013 researchers found that administration of hydrogen peroxide producing strains, such as L. acidophilus and L. rhamnosus, were able to normalize vaginal pH and rebalance vaginal flora, preventing and alleviating bacterial vaginosis.[68]

Blood pressure[edit]

The consumption of probiotics may modestly help to control high blood pressure.[69]

Cholesterol[edit]

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).[70][71]

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.[72]

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.[73]

Studies specifically on hyperlipidemic subjects are still needed.

Diarrhea[edit]

Some probiotics are suggested as a possible treatment for various forms of gastroenteritis,[74] 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.[75][76]

Eczema[edit]

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.[58]

Helicobacter pylori[edit]

Some strains of lactic acid bacteria 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.[77]

Immune function and infections[edit]

Some strains of lactic acid bacteria (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.[78][79] Clinical trials have demonstrated that probiotics may decrease the incidence of respiratory-tract infections[80] and dental caries in children.[81] LAB products might aid in the treatment of acute diarrhea, and possibly affect rotavirus infections in children and travelers' diarrhea in adults,[78][79] but no products are approved for such indications.

Inflammation[edit]

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.[78] Clinical studies are assessing whether they can prevent recurrences of inflammatory bowel disease in adults,[78] as well as affect milk allergies.[82] How probiotics may influence the immune system remains unclear.[83]

Inflammatory bowel disease[edit]

Probiotics are being studied for their potential to influence inflammatory bowel disease. There is some evidence to support their use in conjunction with standard medications in treating ulcerative colitis and no evidence of their efficacy in treating Crohn's disease.[84][85][86]

A live formulation of lyophilized Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus paracasei, Lactobacillus bulgaricus, and Streptococcus thermophilus (VSL#3) has shown effectiveness in the small clinical trials, some of which were not randomized nor double-blinded, that had been done as of 2015; more high-quality clinical trials are needed to determine safety and effectiveness.[84][85]

Irritable bowel syndrome[edit]

Probiotics are under study for their potential to affect irritable bowel syndrome, although uncertainty remains around which type of probiotic works best, and around the size of possible effect.[84][87]

Lactose intolerance[edit]

Ingestion of certain active strains may help lactose-intolerant individuals tolerate more lactose than they would otherwise have tolerated.[70]

Necrotizing enterocolitis[edit]

Several clinical studies provide evidence for the potential of probiotics to lower the risk of necrotizing enterocolitis and mortality in premature infants. One meta-analysis indicated that probiotics reduce these risks by more than 50% compared with controls.[88]

Recurrent abdominal pain[edit]

A 2017 review based on moderate to low-quality evidences suggests that probiotics may be helpful in relieving pain in the short term in children with recurrent abdominal pain, but the proper strain and dosage are not known.[89]

Urinary tract[edit]

There is no good evidence that probiotics are of benefit in the management of infection or inflammation of the urinary tract.[90]

Vitamin production[edit]

Probiotic treatment has been studied as a means of addressing disorders associated with vitamin deficiencies including those of vitamin K,[91] folic acid,[92] and vitamin B12.[93]

Side effects[edit]

The manipulation of the gut microbiota is complex and may cause bacteria-host interactions.[11] Although probiotics are considered to be safe, there are concerns about their safety in certain cases.[11][94] Some people, such as those with immunodeficiency, short bowel syndrome, central venous catheters, cardiac valve disease and premature infants, may be at higher risk for adverse events.[9] In severely ill people with inflammatory bowel disease there is a risk of 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.[11] 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.[10]

It has been suggested that Lactobacillus contributes to obesity in humans, but no evidence of this relationship has been found.[95]

Strains[edit]

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. 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.[96]

There is only preliminary evidence 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 by a regulatory agency such as the Food and Drug Administration or European Food Safety Authority, and, as of 2010, no claims had been approved by those two agencies.[2] Some experts are skeptical about the efficacy of different strains, and believe that not all subjects will benefit from the use of probiotics.[2][97]

Some fermented products contain lactic acid bacteria, including pickled vegetables,[98] tempeh,[99] miso,[100] kefir,[101] buttermilk or karnemelk,[102] kimchi,[98][103] pao cai,[104] sauerkraut,[105] and soy sauce.[106]

Commercial probiotics[edit]

Labeling[edit]

The US National Yogurt Association gives a Live & Active Cultures Seal to refrigerated yogurt products which contain 100 million cultures per gram or frozen yogurt products containing 10 million cultures per gram at the time of manufacture.[107] In 2002, the US Food and Drug Administration (FDA) and World Health Organization recommended that “the minimum viable numbers of each probiotic strain at the end of the shelf-life” be reported on labeling,[108] 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.[109] 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, 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.[2][110][111][112]

In the United States, the FDA and Federal Trade Commission have issued warning letters and imposed punishment on various manufacturers of probiotic products whose labels claim to treat a disease or condition.[7][8][41]

History and modern products[edit]

The first commercially sold dairy-based probiotic was Yakult, a fermented milk with added Lactobacillus casei Shirota, in 1935.[113] Since then many more probiotic foods have come on the market, mostly dairy products. Non-dairy and unfermented probiotics have been produced, including breakfast cereals and snack bars, in addition to traditional fermented products such as kefir, yogurt, kombucha, kimchi, and sauerkraut.[114][115]

Global consumption[edit]

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.[116] 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.[116] 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).[116]

Multiple probiotics[edit]

Preliminary research is evaluating the potential physiological effects of multiple probiotic strains, as opposed to a single strain.[117][118] 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.

See also[edit]

References[edit]

  1. ^ a b Hill, C; Guarner, F; Reid, G; Gibson, GR; Merenstein, DJ; Pot, B; Morelli, L; Canani, RB; Flint, HJ; Salminen, S; Calder, PC; Sanders, ME (August 2014). "Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic". Nature Reviews. Gastroenterology & Hepatology. 11 (8): 506–14. doi:10.1038/nrgastro.2014.66. PMID 24912386. 
  2. ^ a b c d e f g h i j k l Rijkers GT, de Vos WM, Brummer RJ, Morelli L, Corthier G, Marteau P (2011). "Health benefits and health claims of probiotics: Bridging science and marketing". British Journal of Nutrition. 106 (9): 1291–6. doi:10.1017/S000711451100287X. PMID 21861940. 
  3. ^ 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, Argentina, 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 [1], accessed 11 June 2015.
  4. ^ Brown, Amy C.; Valiere, Ana (2004-01-01). "Probiotics and Medical Nutrition Therapy". Nutrition in clinical care : an official publication of Tufts University. 7 (2): 56–68. ISSN 1096-6781. PMC 1482314Freely accessible. PMID 15481739. 
  5. ^ a b Élie [Ilya Ilyich] Metchnikoff, 2004 [1907], The prolongation of life: Optimistic studies, p. 116. 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, Retrieved 12 November 2015.
  6. ^ a b Slashinski MJ, McCurdy SA, Achenbaum LS, Whitney SN, McGuire AL (2012). ""Snake-oil," "quack medicine," and "industrially cultured organisms:" biovalue and the commercialization of human microbiome research". BMC Medical Ethics. 13: 28. doi:10.1186/1472-6939-13-28. PMC 3512494Freely accessible. PMID 23110633. 
  7. ^ a b c Engle MK, Roosevelt MW, Waltrip EA (22 November 2011). "Warning letter to CocoKefir LLC". Compliance Branch, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration and Federal Trade Commission. Retrieved 4 June 2016. 
  8. ^ a b c "Dannon Agrees to Drop Exaggerated Health Claims for Activia Yogurt and DanActive Dairy Drink FTC Charges that Evidence Supporting Benefits of Probiotics Falls Short". Federal Trade Commission, US Government. 15 December 2010. Retrieved 9 May 2017. 
  9. ^ a b Doron S, Snydman DR (2015). "Risk and safety of probiotics". Clin Infect Dis (Review). 60 Suppl 2: S129–34. doi:10.1093/cid/civ085. PMC 4490230Freely accessible. PMID 25922398. 
  10. ^ a b Singhi SC, Kumar S (2016). "Probiotics in critically ill children". F1000Res (Review). 5: 407. doi:10.12688/f1000research.7630.1. PMC 4813632Freely accessible. PMID 27081478. 
  11. ^ a b c d Durchschein F, Petritsch W, Hammer HF (2016). "Diet therapy for inflammatory bowel diseases: The established and the new". World J Gastroenterol (Review). 22 (7): 2179–94. doi:10.3748/wjg.v22.i7.2179. PMC 4734995Freely accessible. PMID 26900283. 
  12. ^ Fuller, R., ed. (1992) Probiotics. The Scientific Basis. Chapman & Hall, London, U.K
  13. ^ Alvarez-Olmos MI, Oberhelman RA (2001). "Probiotic agents and infectious diseases: a modern perspective on a traditional therapy". Clin. Infect. Dis. 32 (11): 1567–76. doi:10.1086/320518. PMID 11340528. 
  14. ^ Liddell, Henry George; Scott, Robert (eds.). "βιωτικός". A Greek-English Lexicon – via Perseus Project. 
  15. ^ Hamilton-Miller JM, Gibson GR, Bruck W (October 2003). "Some insights into the derivation and early uses of the word 'probiotic'". Br. J. Nutr. 90 (4): 845. doi:10.1079/BJN2003954. PMID 14552330. 
  16. ^ Schlundt, Jorgen. "Health and Nutritional Properties of Probiotics in Food including Powder Milk with Live Lactic Acid Bacteria" (PDF). 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. FAO / WHO. Archived from the original (PDF) on October 22, 2012. Retrieved 17 December 2012. 
  17. ^ 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 (2010). "Guidance for substantiating the evidence for beneficial effects of probiotics: current status and recommendations for future research". J. Nutr. 140 (3): 671S–6S. doi:10.3945/jn.109.113779. PMID 20130080. 
  18. ^ Shane AL, Cabana MD, Vidry S, Merenstein D, Hummelen R, Ellis CL, Heimbach JT, Hempel S, Lynch SV, Sanders ME, et al. (2010). ": Guide to designing, conducting, publishing and communicating results of clinical studies involving probiotic applications in human participants". Gut Microbes. 1 (4): 243–253. doi:10.4161/gmic.1.4.12707. PMC 3023606Freely accessible. PMID 21327031. 
  19. ^ "Guidelines for the Evaluation of Probiotics in Food" (PDF). Joint FAO/WHO Working Group on Drafting Guidelines for the Evaluation of Probiotics in Food, London, Ontario, Canada. 1 May 2002. 
  20. ^ a b c d Fuller R (May 1989). "Probiotics in man and animals". The Journal of Applied Bacteriology. 66 (5): 365–78. doi:10.1111/j.1365-2672.1989.tb05105.x. PMID 2666378. 
  21. ^ a b Fuller R (1991). "Probiotics in human medicine". Gut. 32 (4): 439–42. doi:10.1136/gut.32.4.439. PMC 1379087Freely accessible. PMID 1902810. 
  22. ^ Fuller R. Probiotics the Scientific Thesis. London: Chapman & Hall, 1992
  23. ^ Reid G, Gaudier E, Guarner F, Huffnagle GB, Macklaim JM, Munoz AM, Martini M, Ringel-Kulka T, Sartor B, Unal R, Verbeke K, Walter J (2010). "Responders and non-responders to probiotic interventions: how can we improve the odds?". Gut Microbes. 1 (3): 200–4. doi:10.4161/gmic.1.3.12013. PMC 3023600Freely accessible. PMID 21637034. 
  24. ^ O'Hara AM, O'Regan P, Fanning A, O'Mahony C, Macsharry J, Lyons A, Bienenstock J, O'Mahony L, Shanahan F (2006). "Functional modulation of human intestinal epithelial cell responses by Bifidobacterium infantis and Lactobacillus salivarius". Immunology. 118 (2): 202–15. doi:10.1111/j.1365-2567.2006.02358.x. PMC 1782284Freely accessible. PMID 16771855. 
  25. ^ Huys, G; Botteldoorn, N; Delvigne, F; Vuyst, L. D.; Heyndrickx, M; Pot, B; Dubois, J. J.; Daube, G (2013). "Microbial characterization of probiotics–Advisory report of the Working Group "8651 Probiotics" of the Belgian Superior Health Council (SHC)". Molecular Nutrition & Food Research. 57 (8): 1479–1504. doi:10.1002/mnfr.201300065. PMC 3910143Freely accessible. 
  26. ^ "Commentary by the Scientific Committee on Animal Nutrition on Data Relating to Toxin Production" (PDF). Scientific Opinion. European Commission, Health & Consumer Protection Directorate-General. December 2001. Retrieved 5 June 2016. 
  27. ^ Introduction of a Qualified Presumption of Safety (QPS) approach for assessment of selected microorganisms referred to EFSA Archived July 23, 2015, at the Wayback Machine.
  28. ^ Gismondo MR, Drago L, Lombardi A (1999). "Review of probiotics available to modify gastrointestinal flora". Int. J. Antimicrob. Agents. 12 (4): 287–92. doi:10.1016/s0924-8579(99)00050-3. PMID 10493604. 
  29. ^ Azizpour K, Bahrambeygi S, Mahmoodpour S (2009). "History and Basic of Probiotics". Research Journal of Biological Sciences. 4 (4): 409–426. 
  30. ^ Arteriosclerosis and intestinal poisons. [a contemporary review of Metchnikoff's work] JAMA 1910, 55:2311-12.
  31. ^ Vaughan RB (July 1965). "The romantic rationalist: A study of Elie Metchnikoff". Medical History. 9 (3): 201–15. doi:10.1017/S0025727300030702. PMC 1033501Freely accessible. PMID 14321564. 
  32. ^ Tissier, H. 1900. Recherchers sur la flora intestinale normale et pathologique du nourisson. Thesis, University of Paris, Paris, France.
  33. ^ Nißle Alfred (1918). "Die antagonistische Behandlung chronischer Darmstörungen mit Colibakterien". Medizinische Klinik. 1918 (2): 29–33. 
  34. ^ a b Cheplin HA, Rettger LF (December 1920). "Studies on the Transformation of the Intestinal Flora, with Special Reference to the Implantation of Bacillus Acidophilus: II. Feeding Experiments on Man". Proceedings of the National Academy of Sciences of the United States of America. 6 (12): 704–5. Bibcode:1920PNAS....6..704C. doi:10.1073/pnas.6.12.704. PMC 1084701Freely accessible. PMID 16576567. [non-primary source needed]
  35. ^ Rettger, L.F., W.N. Levy, L. Weinstein, and J.E. Weiss. 1935. Lactobacillus acidophilus and its therapeutic application. Yale University Press, New Haven.[non-primary source needed]
  36. ^ Lilly DM, Stillwell RH (1965). "Probiotics: Growth-promoting factors produced by microorganisms". Science. New York, N.Y. 147 (3659): 747–748. Bibcode:1965Sci...147..747L. doi:10.1126/science.147.3659.747. PMID 14242024. 
  37. ^ Sperti, G. S. (1971). Probiotics. West Point, CT: AVI Publishing Co. ISBN 0870550993. 
  38. ^ Parker, R. B. (1974). "Probiotics, the other half of the antibiotic story". Animal Nutrition and Health. 29: 4–8. 
  39. ^ Tannock GW (September 2003). "Probiotics: time for a dose of realism". Current Issues in Intestinal Microbiology. 4 (2): 33–42. PMID 14503687. 
  40. ^ a b c "Scientific Opinion on the substantiation of a health claim related to a combination of Bifidobacterium longum LA 101, Lactobacillus helveticus LA 102, Lactococcus lactis LA 103 and Streptococcus thermophillus LA 104 and reducing intestinal discomfort pursuant to Article 13(5) of Regulation (EC) No 1924/2006 (example, search EFSA for other opinion reports on probiotics" (PDF). European Food Safety Authority, EFSA Journal 2013;11(2):3085. Archived from the original (PDF) on November 29, 2014. Retrieved 2012-11-08. 
  41. ^ a b Schmidt, Nancy, Acting Director (30 July 2014). "Warning letter to Plexus Worldwide Inc". Compliance Branch, Inspections, Compliance, Enforcement, and Criminal Investigations, US Food and Drug Administration. Retrieved 9 May 2017. 
  42. ^ Bermudez-Brito, M; Plaza-Díaz, J; Muñoz-Quezada, S; Gómez-Llorente, C; Gil, A (2012). "Probiotic mechanisms of action". Annals of Nutrition and Metabolism. 61 (2): 160–74. doi:10.1159/000342079. PMID 23037511. 
  43. ^ Salminen S, van Loveren H (2012). "Probiotics and prebiotics: health claim substantiation". Microb Ecol Health Dis. 23. doi:10.3402/mehd.v23i0.18568. PMC 3747744Freely accessible. PMID 23990821. 
  44. ^ Gueimonde M, Collado MC (2012). "Metagenomics and probiotics". Clinical Microbiology and Infection. 18 Suppl 4: 32–4. doi:10.1111/j.1469-0691.2012.03873.x. PMID 22647045. 
  45. ^ Mach T (November 2006). "Clinical usefulness of probiotics against chronic inflammatory bowel diseases". Journal of Physiology and Pharmacology. 57 Suppl 9: 23–33. PMID 17242485. 
  46. ^ Yan F, Polk DB (November 2006). "Probiotics as functional food in the treatment of diarrhea". Current Opinion in Clinical Nutrition and Metabolic Care. 9 (6): 717–21. doi:10.1097/01.mco.0000247477.02650.51. PMID 17053425. 
  47. ^ Reid G (September 2008). "Probiotic Lactobacilli for urogenital health in women". J. Clin. Gastroenterol. 42 (Suppl 3 Pt 2): S234–6. doi:10.1097/MCG.0b013e31817f1298. PMID 18685506. 
  48. ^ Ljungh A, Wadstrom T, eds. (2009). Lactobacillus Molecular Biology: From Genomics to Probiotics. Caister Academic Press. ISBN 978-1904455417. [page needed]
  49. ^ Gilliland SE, Walker DK (April 1990). "Factors to consider when selecting a culture of Lactobacillus acidophilus as a dietary adjunct to produce a hypocholesterolemic effect in humans". Journal of Dairy Science. 73 (4): 905–11. doi:10.3168/jds.S0022-0302(90)78747-4. PMID 2111831. [unreliable medical source?]
  50. ^ "Health and Nutritional Properties of Probiotics in Food including Powder Milk with Live Lactic Acid Bacteria" (PDF). Food and Agriculture Organization of the United Nations. October 2001. Archived from the original (PDF) on May 14, 2012. Retrieved May 14, 2012. 
  51. ^ Rowland I, Capurso L, Collins K, Cummings J, Delzenne N, Goulet O, Guarner F, Marteau P, Meier R (2010). "Current level of consensus on probiotic science: Report of an expert meeting-London, 23 November 2009". Gut Microbes. 1 (6): 436–439. doi:10.4161/gmic.1.6.13610. PMC 3056112Freely accessible. PMID 21637035. 
  52. ^ Sears, Cynthia L. (2005). "A dynamic partnership: Celebrating our gut flora". Anaerobe. 11 (5): 247–51. doi:10.1016/j.anaerobe.2005.05.001. PMID 16701579. 
  53. ^ Wu, G. D.; Chen, J.; Hoffmann, C.; Bittinger, K.; Chen, Y.-Y.; Keilbaugh, S. A.; Bewtra, M.; Knights, D.; Walters, W. A.; Knight, R.; Sinha, R.; Gilroy, E.; Gupta, K.; Baldassano, R.; Nessel, L.; Li, H.; Bushman, F. D.; Lewis, J. D. (2011). "Linking Long-Term Dietary Patterns with Gut Microbial Enterotypes". Science. 334 (6052): 105–8. Bibcode:2011Sci...334..105W. doi:10.1126/science.1208344. PMC 3368382Freely accessible. PMID 21885731. 
  54. ^ Million M, Raoult D (February 2013). "Species and strain specificity of Lactobacillus probiotics effect on weight regulation". Microbial Pathogenesis. 55: 52–4. doi:10.1016/j.micpath.2012.09.013. PMID 23332210. 
  55. ^ Million M, Angelakis E, Paul M, Armougom F, Leibovici L, Raoult D (August 2012). "Comparative meta-analysis of the effect of Lactobacillus species on weight gain in humans and animals". Microbial Pathogenesis. 53 (2): 100–8. doi:10.1016/j.micpath.2012.05.007. PMID 22634320. 
  56. ^ Lahtinen SJ, Davis E, Ouwehand AC (September 2012). "Lactobacillus species causing obesity in humans: where is the evidence?". Beneficial Microbes. 3 (3): 171–4. doi:10.3920/BM2012.0041. PMID 22968407. 
  57. ^ "Probiotics: In Depth". NCCIH. Retrieved 2017-07-13. 
  58. ^ a b Cuello-Garcia CA, Brożek JL, Fiocchi A, Pawankar R, Yepes-Nuñez JJ, Terracciano L, Gandhi S, Agarwal A, Zhang Y, Schünemann HJ (2015). "Probiotics for the prevention of allergy: A systematic review and meta-analysis of randomized controlled trials". J. Allergy Clin. Immunol. (Systematic review & meta-analysis). 136 (4): 952–61. doi:10.1016/j.jaci.2015.04.031. PMID 26044853. 
  59. ^ a b Goldenberg, Joshua Z.; Lytvyn, Lyubov; Steurich, Justin; Parkin, Patricia; Mahant, Sanjay; Johnston, Bradley C. (2015-12-22). "Probiotics for the prevention of pediatric antibiotic-associated diarrhea". The Cochrane Database of Systematic Reviews (12): CD004827. doi:10.1002/14651858.CD004827.pub4. ISSN 1469-493X. PMID 26695080. 
  60. ^ McFarland LV (2006). "Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease". Am. J. Gastroenterol. 101 (4): 812–22. doi:10.1111/j.1572-0241.2006.00465.x. PMID 16635227. 
  61. ^ McFarland LV (April 2006). "Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease". Am J Gastroenterol. 101 (4): 812–22. doi:10.1111/j.1572-0241.2006.00465.x. PMID 16635227. 
  62. ^ Szajewska H, Ruszczyński M, Radzikowski A (September 2006). "Probiotics in the prevention of antibiotic-associated diarrhea in children: a meta-analysis of randomized controlled trials". J Pediatr. 149 (3): 367–372. doi:10.1016/j.jpeds.2006.04.053. PMID 16939749. 
  63. ^ Sazawal S, Hiremath G, Dhingra U, Malik P, Deb S, Black RE (June 2006). "Efficacy of probiotics in prevention of acute diarrhoea: a meta-analysis of masked, randomised, placebo-controlled trials". Lancet Infect Dis. 6 (6): 374–82. doi:10.1016/S1473-3099(06)70495-9. PMID 16728323. 
  64. ^ Arvola T, Laiho K, Torkkeli S, Mykkänen H, Salminen S, Maunula L, Isolauri E (1999). "Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhea in children with respiratory infections: A randomized study". Pediatrics. 104 (5): e64. doi:10.1542/peds.104.5.e64. PMID 10545590. 
  65. ^ Doron SI, Hibberd PL, Gorbach SL (July 2008). "Probiotics for prevention of antibiotic-associated diarrhea". J Clin Gastroenterol. 42 (Suppl 2): S58–63. doi:10.1097/MCG.0b013e3181618ab7. PMID 18542041. 
  66. ^ Surawicz CM (July 2008). "Role of probiotics in antibiotic-associated diarrhea, Clostridium difficile-associated diarrhea, and recurrent Clostridium difficile-associated diarrhea". J Clin Gastroenterol. 42 (Suppl 2): S64–70. doi:10.1097/MCG.0b013e3181646d09. PMID 18545161. 
  67. ^ Petrova, Mariya I.; Lievens, Elke; Malik, Shweta; Imholz, Nicole; Lebeer, Sarah (2015). "Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health". Frontiers in Physiology. 6. doi:10.3389/fphys.2015.00081. ISSN 1664-042X. 
  68. ^ Borges S, Silva J, Teixeira P (March 2014). "The role of lactobacilli and probiotics in maintaining vaginal health". Arch. Gynecol. Obstet. (Review). 289 (3): 479–89. doi:10.1007/s00404-013-3064-9. PMID 24170161. 
  69. ^ Khalesi S, Sun J, Buys N, Jayasinghe R (2014). "Effect of probiotics on blood pressure: a systematic review and meta-analysis of randomized, controlled trials". Hypertension (Systematic review & meta-analysis). 64 (4): 897–903. doi:10.1161/HYPERTENSIONAHA.114.03469. PMID 25047574. 
  70. ^ a b Sanders ME (February 2000). "Considerations for use of probiotic bacteria to modulate human health". The Journal of Nutrition. 130 (2S Suppl): 384S–390S. PMID 10721912. Retrieved 2012-05-14. 
  71. ^ Kumar M, Nagpal R, Kumar R, Hemalatha R, Verma V, Kumar A, Chakraborty C, Singh B, Marotta F, Jain S, Yadav H (2012). "Cholesterol-lowering probiotics as potential biotherapeutics for metabolic diseases". Experimental Diabetes Research. 2012: 902917. doi:10.1155/2012/902917. PMC 3352670Freely accessible. PMID 22611376. 
  72. ^ Agerholm-Larsen L, Bell ML, Grunwald GK, Astrup A (2002). "The effect of a probiotic milk product on plasma cholesterol: a meta-analysis of short term intervention studies". European Journal of Clinical Nutrition. 54 (11): 856–860. doi:10.1038/sj.ejcn.1601104. PMID 11114681. 
  73. ^ Kiessling G, Schneider J, Jahreis G (2002). "Long term consumption of fermented dairy products over 6 months increases HDL cholesterol". European Journal of Clinical Nutrition. 56 (9): 843–849. doi:10.1038/sj.ejcn.1601399. PMID 12209372. 
  74. ^ King CK, Glass R, Bresee JS, Duggan C (November 2003). "Managing acute gastroenteritis among children: oral rehydration, maintenance, and nutritional therapy". MMWR Recomm Rep. 52 (RR–16): 1–16. PMID 14627948. 
  75. ^ Allen SJ, Martinez EG, Gregorio GV, Dans LF (2010). Allen SJ, ed. "Probiotics for treating acute infectious diarrhea". Cochrane Database Syst Rev. 11 (11): CD003048. doi:10.1002/14651858.CD003048.pub3. PMID 21069673. 
  76. ^ "Probiotics 'ease upset stomachs'". NHS Choices. 2010. Retrieved 28 October 2013. 
  77. ^ Hamilton-Miller JM (October 2003). "The role of probiotics in the treatment and prevention of Helicobacter pylori infection". International Journal of Antimicrobial Agents. 22 (4): 360–6. doi:10.1016/S0924-8579(03)00153-5. PMID 14522098. 
  78. ^ a b c d Reid G, Jass J, Sebulsky MT, McCormick JK (October 2003). "Potential uses of probiotics in clinical practice". Clin. Microbiol. Rev. 16 (4): 658–72. doi:10.1128/CMR.16.4.658-672.2003. PMC 207122Freely accessible. PMID 14557292. 
  79. ^ a b Ouwehand AC, Salminen S, Isolauri E (August 2002). "Probiotics: an overview of beneficial effects" (PDF). Antonie Van Leeuwenhoek. 82 (1–4): 279–89. doi:10.1023/A:1020620607611. PMID 12369194. Retrieved 2012-05-14. 
  80. ^ Hatakka K, Savilahti E, Pönkä A, Meurman JH, Poussa T, Näse L, Saxelin M, Korpela R (June 2001). "Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial". BMJ. 322 (7298): 1327. doi:10.1136/bmj.322.7298.1327. PMC 32161Freely accessible. PMID 11387176. 
  81. ^ Näse L, Hatakka K, Savilahti E, Saxelin M, Pönkä A, Poussa T, Korpela R, Meurman JH (2001). "Effect of long-term consumption of a probiotic bacterium, Lactobacillus rhamnosus GG, in milk on dental caries and caries risk in children". Caries Research. 35 (6): 412–20. doi:10.1159/000047484. PMID 11799281. 
  82. ^ Kirjavainen PV, Salminen SJ, Isolauri E (February 2003). "Probiotic bacteria in the management of atopic disease: underscoring the importance of viability". J. Pediatr. Gastroenterol. Nutr. 36 (2): 223–7. doi:10.1097/00005176-200302000-00012. PMID 12548058. 
  83. ^ Braat H, van den Brande J, van Tol E, Hommes D, Peppelenbosch M, van Deventer S (2004). "Lactobacillus rhamnosus induces peripheral hyporesponsiveness in stimulated CD4+ T cells via modulation of dendritic cell function". The American Journal of Clinical Nutrition. 80 (6): 1618–25. PMID 15585777. 
  84. ^ a b c Maria Jose Saez-Lara; Carolina Gomez-Llorente; Julio Plaza-Diaz; Angel Gil (2015). "The Role of Probiotic Lactic Acid Bacteria and Bifidobacteria in the Prevention and Treatment of Inflammatory Bowel Disease and Other Related Diseases: A Systematic Review of Randomized Human Clinical Trials". Biomed Res Int (Systematic review). 2015: 15. doi:10.1155/2015/505878. PMC 4352483Freely accessible. PMID 25793197. 
  85. ^ a b "Probiotics and prebiotics. World Gastroenterology Organisation Global Guidelines" (PDF). World Gastroenterology Organisation. October 2011. Retrieved 1 June 2016. 
  86. ^ Ghouri YA, Richards DM, Rahimi EF, Krill JT, Jelinek KA, DuPont AW (Dec 9, 2014). "Systematic review of randomized controlled trials of probiotics, prebiotics, and synbiotics in inflammatory bowel disease". Clin Exp Gastroenterol (Review). 7: 473–87. doi:10.2147/CEG.S27530. PMC 4266241Freely accessible. PMID 25525379. 
  87. ^ Moayyedi P, Ford AC, Talley NJ, Cremonini F, Foxx-Orenstein AE, Brandt LJ, Quigley EM (March 2010). "The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review". Gut (Systematic review). 59 (3): 325–32. doi:10.1136/gut.2008.167270. PMID 19091823. 
  88. ^ AlFaleh K. & Anabrees J., 2014, "Probiotics for prevention of necrotizing enterocolitis in preterm infants." Cochrane Database of Systematic Reviews Issue 4, Art. No.: CD005496, doi:10.1002/14651858.CD005496.pub4, see [2], accessed 11 June 2015.
  89. ^ Newlove-Delgado TV, Martin AE, Abbott RA, Bethel A, Thompson-Coon J, Whear R, et al. (2017). "Dietary interventions for recurrent abdominal pain in childhood". Cochrane Database Syst Rev. 3: CD010972. doi:10.1002/14651858.CD010972.pub2. PMID 28334433. Overall, there is some evidence to suggest that probiotics may be effective in the treatment of RAP, in terms of improving pain in the shorter term. Clinicians may therefore consider probiotic interventions as part of themanagement strategy for children with RAP (Recurrent Abdominal Pain). However, we were unable to recommend the optimum strain and dosage of probiotic based on this review. The evidence for the effectiveness of probiotics was based largely on shorter-term outcomes. Further trials are required to assess whether improvements in pain are maintained over the longer term; these trials should also consider the importance of using validated and consistent scales to measure pain and other outcomes. 
  90. ^ Shortliffe LMD (2013). Wein AJ, ed. Chapter 116: Infection and Inflammation of the Pediatric Genitourinary Tract. Urology. 4 (10th ed.). Saunders Elsevier. p. 3121. 
  91. ^ Cooke, G.; Behan, J.; Costello, M. (2006). "Newly identified vitamin K-producing bacteria isolated from the neonatal faecal flora". Microbial Ecology in Health and Disease. 18 (3–4): 133–138. doi:10.1080/08910600601048894. 
  92. ^ Strozzi GP, Mogna L (2008). "Quantification of Folic Acid in Human Feces After Administration of Bifidobacterium Probiotic Strains". Journal of Clinical Gastroenterology. 42: S179–S184. doi:10.1097/MCG.0b013e31818087d8. PMID 18685499. 
  93. ^ Molina VC, Médici M, Taranto MP, Font de Valdez G (2009). "Lactobacillus reuteriCRL 1098 prevents side effects produced by a nutritional vitamin B12deficiency". Journal of Applied Microbiology. 106 (2): 467–473. doi:10.1111/j.1365-2672.2008.04014.x. PMID 19200314. 
  94. ^ Boyle RJ, Robins-Browne RM, Tang ML (2006). "Probiotic use in clinical practice: what are the risks?". Am J Clin Nutr (Review). 83 (6): 1256–64; quiz 1446–7. PMID 16762934. 
  95. ^ Lahtinen SJ, Davis E, Ouwehand AC (2012). "Lactobacillus species causing obesity in humans: where is the evidence?". Benef Microbes (Review). 3 (3): 171–4. doi:10.3920/BM2012.0041. PMID 22968407. 
  96. ^ Islam MA, Yun CH, Choi YJ, Cho CS (2010). "Microencapsulation of live probiotic bacteria" (PDF). Journal of Microbiology and Biotechnology. 20 (1367–1377): 1367–1377. doi:10.4014/jmb.1003.03020. PMID 21030820. 
  97. ^ Bee, Peta (November 10, 2008). "Probiotics, not so friendly after all?". The Times. London. Retrieved 18 June 2010. 
  98. ^ a b Breidt F, McFeeters RF, Perez-Diaz I, Lee CH (2013). "Fermented Vegetables; In: Food Microbiology: Fundamentals and Frontiers, 4th Ed" (PDF). Washington, DC: ASM Press. doi:10.1128/9781555818463.ch33. Retrieved 19 May 2016. 
  99. ^ Moreno MR, Leisner JJ, Tee LK, Ley C, Radu S, Rusul G, Vancanneyt M, De Vuyst L (2002). "Microbial analysis of Malaysian tempeh, and characterization of two bacteriocins produced by isolates of Enterococcus faecium". Journal of Applied Microbiology. The Microbiology Research Foundation. 92 (1): 147–157. doi:10.1046/j.1365-2672.2002.01509.x. PMID 11849339. Retrieved 7 November 2007. 
  100. ^ Ehrlich, Steven D. (2011-05-24). "Lactobacillus acidophilus". University of Maryland Medical Center (UMMC). Retrieved 2015-09-17. 
  101. ^ Plessas S, Alexopoulos A, Voidarou C, Stavropoulou E, Bezirtzoglou E (2011). "Microbial ecology and quality assurance in food fermentation systems. The case of kefir grains application". Anaerobe. 17 (6): 483–5. doi:10.1016/j.anaerobe.2011.03.014. PMID 21497663. 
  102. ^ Shiby VK, Mishra HN (2013). "Fermented milks and milk products as functional foods--a review". Critical reviews in food science and nutrition. 53 (5): 482–96. doi:10.1080/10408398.2010.547398. PMID 23391015. 
  103. ^ Oh CK, Oh MC, Kim SH (2004). "The Depletion of Sodium Nitrite by Lactic Acid Bacteria Isolated from Kimchi". Journal of Medicinal Food. Mary Ann Liebert. 7 (1): 38–44. doi:10.1089/109662004322984680. PMID 15117551. Retrieved 7 November 2007. 
  104. ^ Pederson CS, Niketic G, Albury MN (1962). "Fermentation of the Yugoslavian pickled cabbage". Applied microbiology. 10 (1): 86–9. PMC 1057814Freely accessible. PMID 14484853. 
  105. ^ Friedman, Y; Hugenholtz, Jeroen; De Vos, Willem M.; Smid, Eddy J. (2006). "Safe use of genetically modified lactic acid bacteria in food. Bridging the gap between consumers, green groups, and industry". Electronic Journal of Biotechnology. Pontificia Universidad Católica de Valparaíso. 9 (4): E49–55. doi:10.2225/vol9-issue4-fulltext-12. Retrieved 7 November 2007. 
  106. ^ Tanasupawat S, Thongsanit J, Okada S, Komagata K (2002). "Lactic acid bacteria isolated from soy sauce mash in Thailand". Journal of General and Applied Microbiology. The Microbiology Research Foundation. 48 (4): 201–209. doi:10.2323/jgam.48.201. PMID 12469319. 
  107. ^ "Live & Active Culture Yogurt". National Yogurt Association. Retrieved 12 December 2014. 
  108. ^ Guidelines for the Evaluation of Probiotics in Food, Report of a Joint FAO/WHO Working Group on Drafting Guidelines for the Evaluation of Probiotics in Food (PDF) (Report). London, Ontario, Canada: Food and Agriculture Organization and World Health Organization. April 2002. Retrieved 12 December 2014. 
  109. ^ Sanders, ME (2000). "Considerations for Use of Probiotic Bacteria to Modulate Human Health". The Journal of Nutrition. 130 (2S Suppl): 384S–390S. PMID 10721912. Retrieved 12 December 2014. 
  110. ^ ‘Probiotic’ As A General Descriptor (PDF) (Report). Yogurt & Live Fermented Milks Association (YLFA). Retrieved 12 December 2014. 
  111. ^ "Regulation (EC) No 1924/2006 of the European Parliament and of the Council on 20 December 2006 on nutrition and health claims made on foods". European Commission, Brussels. 2006. Retrieved 13 December 2014. 
  112. ^ "Probiotic health claims". Food Safety Authority of Ireland, Dublin. 2014. Retrieved 13 December 2014. 
  113. ^ "Our history". Yakult Honsha, Japan. 2017. Retrieved 4 February 2017. 
  114. ^ "Bifidobacterium". WebMD. 2014. Retrieved 12 December 2014. 
  115. ^ May, Gareth (11 June 2015). "Fermented food: everything you need to know for your health". The Telegraph, Telegraph Media Group Limited, London, UK. Retrieved 4 February 2017. 
  116. ^ a b c "Probiotic market: global sales by region 2010-2015 (fee-based)". Statista. 2014. Retrieved 12 December 2014. (registration required)
  117. ^ Timmerman HM, Koning CJ, Mulder L, Rombouts FM, Beynen AC (November 2004). "Monostrain, multistrain and multispecies probiotics—A comparison of functionality and efficacy". Int. J. Food Microbiol. 96 (3): 219–33. doi:10.1016/j.ijfoodmicro.2004.05.012. PMID 15454313. 
  118. ^ Williams EA, Stimpson J, Wang D, Plummer S, Garaiova I, Barker ME, Corfe BM (September 2008). "Clinical trial: a multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study". Aliment. Pharmacol. Ther. 29 (1): 97–103. doi:10.1111/j.1365-2036.2008.03848.x. PMID 18785988. 

Further reading[edit]

  • Francisco Guarner, Gabriela Perdigon, Gérard 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 [3], accessed 11 June 2015.