Probiotic

Probiotics are live microorganisms thought to be beneficial to the host organism. According to the currently adopted definition by FAO/WHO, probiotics are: "Live microorganisms which when administered in adequate amounts confer a health benefit on the host".^[1] Lactic acid bacteria (LAB) and bifidobacteria are the most common types of microbes used as probiotics; but certain yeasts and bacilli may also be helpful. Probiotics are commonly consumed as part of fermented foods with specially added active live cultures; such as in yogurt, soy yogurt, or as dietary supplements.

Etymologically, 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").^[2]

At the start of the 20th century, probiotics were thought to beneficially affect the host by improving its intestinal microbial balance, thus inhibiting pathogens and toxin producing bacteria.^[3] Today, specific health effects are being investigated and documented including alleviation of chronic intestinal inflammatory diseases,^[4] prevention and treatment of pathogen-induced diarrhea,^[5] urogenital infections,^[6] and atopic diseases.^[7]

To date, the European Food Safety Authority has rejected most claims that are made about probiotic products, saying they are unproven.^[8]

History

The original observation of the positive role played by certain bacteria was first introduced by Russian scientist and Nobel laureate Élie Metchnikoff, who in the beginning of the 20th century 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 auto-intoxication", which caused the physical changes associated with old age.

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 facts, 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.^[9]

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^[10] 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.

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.^[11] Methods of treating infectious diseases were needed at that time when antibiotics were not yet available, and Nissle used the Escherichia coli Nissle 1917 strain in acute gastrointestinal infectious salmonellosis and shigellosis.

In 1920, Rettger demonstrated that Metchnikoff's "Bulgarian Bacillus", later called Lactobacillus delbrueckii subsp. bulgaricus, could not live in the human intestine,^[12] and the fermented food phenomenon petered out. Metchnikoff's theory was disputable (at this stage), and people doubted his theory of longevity.

After Metchnikoff's death in 1916, the centre of activity moved to the United States. It was reasoned that bacteria originating from the gut were more likely to produce the desired effect in the gut, and in 1935 certain strains of Lactobacillus acidophilus were found to be very active when implanted in the human digestive tract.^[13] Trials were carried out using this organism, and encouraging results were obtained especially in the relief of chronic constipation.

The term "probiotics" was first introduced in 1953 by Werner Kollath (see Hamilton-Miller et al. 2003). 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".^[14] Fuller's definition emphasizes the requirement of viability for probiotics and introduces the aspect of a beneficial effect on the host.

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.^[15]

Preliminary research and potential effects

Experiments into the potential health effects of supplemental probiotics include 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.^[16] Testing of a probiotic usually applies to a specific strain under study.^[17]

Diarrhea

Some probiotics have been shown in preliminary research to possibly treat various forms of gastroenteritis.^[18] They might reduce both the duration of illness and the frequency of stools.^[19] Fermented milk products (such as yoghurt) also reduce the duration of symptoms.^[20]

Antibiotic-associated

Antibiotic-associated diarrhea (AAD) 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 an osmotic diarrhea as a result. Another consequence of antibiotic therapy leading to diarrhea is overgrowth of potentially pathogenic organisms such as Clostridium difficile.

Probiotic treatment might reduce the incidence and severity of AAD as indicated in several meta-analyses.^{[21][22][23][24][25][26]} For example, treatment with probiotic formulations including Lactobacillus rhamnosus may reduce the risk of antibiotic-associated diarrhea, improve stool consistency during antibiotic therapy, and enhance the immune response after vaccination.^[27] However, further documentation of these findings through randomized, double blind, placebo-controlled trials are required to confirm specific effects and attain regulatory approval, which currently does not exist.

Potential efficacy of probiotic AAD prevention is dependent on the probiotic strain(s) used and on the dosage.^[28][29] Up to a 50% reduction of AAD occurrence has been found in preliminary studies.^[26] No side-effects have been reported in any of these studies. Caution should, however, be exercised when administering probiotic supplements to immunocompromised individuals or patients who have a compromised intestinal barrier.^{[citation needed]}

Lactose intolerance

As lactic acid bacteria actively convert lactose into lactic acid, ingestion of certain active strains may help lactose intolerant individuals tolerate more lactose than they would have otherwise.^[30]

Colon cancer

In laboratory investigations, some strains of LAB (Lactobacillus delbrueckii subsp. bulgaricus) have demonstrated anti-mutagenic effects thought to be due to their ability to bind with heterocyclic amines, which are carcinogenic substances formed in cooked meat.^[31] Animal studies have demonstrated that some LAB have evidence for acting against colon cancer in rodents, though human data are inconclusive.^[32] Some human trials hypothesize that the strains tested may exert anti-carcinogenic effects by decreasing the activity of an enzyme called β-glucuronidase^[32] (which can generate carcinogens in the digestive system). Lower rates of colon cancer among higher consumers of fermented dairy products have been observed in one population study, but confirmation of such an effect does not exist.^[30]

Cholesterol

Animal studies have demonstrated the efficacy some strains of LAB to be able to lower serum cholesterol levels, presumably by breaking down bile in the gut, thus inhibiting its reabsorption (which enters the blood as cholesterol).^[30]

A meta-analysis that included five double blind trials examining the short term (2-8weeks) effects of a yoghurt 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.^[33]

A slightly longer study evaluating the effect of a yoghurt with probiotic strains on twenty-nine 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 mg/dL (1.28 mmol/L) to 62 mg/dL (1.6 mmol/L) following treatment. This corresponds to a possible improvement of LDL/HDL ratio.^[34]

Studies specifically on hyper-lipidemic subjects are still needed.

Blood pressure

Although not a confirmed effect, some studies have indicated that consumption of milk fermented with various strains of LAB may result in modest reductions in blood pressure, an effect possibly related to the ACE inhibitor-like peptides produced during fermentation.^[30]

Immune function and infections

Some strains of LAB may affect pathogens by means of competitive inhibition (i.e., by competing for growth) and there is evidence to suggest that they may improve immune function by increasing the number of IgA-producing plasma cells, increasing or improving phagocytosis as well as increasing the proportion of T lymphocytes and Natural Killer cells.^[35][36] Clinical trials have demonstrated that probiotics may decrease the incidence of respiratory tract infections^[37] and dental caries in children.^[38] LAB products might aid in the treatment of acute diarrhea, and possibly affect rotavirus infections in children and travelers' diarrhea in adults,^[35][36] but no products are approved for such indications.

A 2010 study suggested that antibiotics may turn the immune system "off" while probiotics turns it back on "idle", possibly more able to quickly react to new infections.^[39]

Helicobacter pylori

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 there is no standard in medical practice or regulatory approval for such treatment.^[40]

Inflammation

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.^[35] Clinical studies suggest that they can prevent reoccurrences of inflammatory bowel disease in adults,^[35] as well as improve milk allergies.^[41] They are not effective for treating eczema, a persistent skin inflammation.^[42] How probiotics may influence the immune system remains unclear, but a potential mechanism under research concerns the response of T lymphocytes to pro-inflammatory stimuli.^[43]

Bacterial growth under stress

In a study done to see the effects of stress on intestinal flora, rats that were fed probiotics had little occurrence of harmful bacteria latched onto their intestines compared to rats that were fed sterile water.^[44]

Irritable bowel syndrome and colitis

In one study, a commercial strain of bifidobacterium infantis improved some symptoms of irritable bowel syndrome in women.^[45] A separate small study showed that a strain of Lactobacillus plantarum, may also be effective in reducing IBS symptoms.^[46] A study focused on Bifidobacterium animalis showed a reduction in discomfort and bloating in individuals with constipation-predominant IBS, as well as helping to normalize stool frequency in said individuals.^[47] For maintenance of remission of ulcerative colitis, Mutaflor (E.coli Nissle 1917) randomized clinical studies showed equivalence of Mutaflor and mesalazine (5-ASAs).^[48]

Other

A study in 2004 testing the immune system of students given either milk or Actimel over a 6-week exam period (3 weeks of studying, 3 weeks of exams) tested 19 different biomarkers. Of these 19 biomarkers, only 2 were shown to be different between the two groups, increased production of lymphocytes, and increased production of CD56 cells. The tests were not blind and show that certain probiotic strains may have no overall effect on the immune system or on its ability.^[49]

A 2007 study at University College Cork in Ireland showed that a diet including milk fermented with Lactobacillus bacteria prevented Salmonella infection in pigs.^[50]

A 2007 clinical study at Imperial College London showed that preventive consumption of a commercially available probiotic drink containing Lactobacillus casei DN-114001 and yoghurt bacteria can reduce the incidence of antibiotic-associated diarrhea and C difficile-associated diarrhea.^[51]

The efficacy and safety of a daily dose of Lactobacillus acidophilus CL1285 in affecting AAD was demonstrated in one study of hospitalized patients.^[52]

A 2011 study found that mice given Lactobacillus rhamnosus JB-1 showed lower levels of stress and anxiety than controls^[53]

Current research is focusing on the molecular biology and genomics of Lactobacillus strains and bifidobacteria. The application of modern whole genome approaches is providing insights into bifidobacterial evolution, while also revealing genetic functions that explain their presence in the particular ecological environment of the gastrointestinal tract.^[54][55]

Factors affecting viability in foods

Some factors, both intrinsic and extrinsic, may influence the survival of probiotics in food, and so have to be considerated in all stages of probiotic food manufacturing.

• physiological state of the added probiotic in the food
• physicochemical conditions of food processing
• physical conditions of product storage, like temperature
• chemical composition of the product, such as content of nutrients, oxygen or pH
• interactions with other product components, that can be inhibitory or protective

Physiological state

The physiological state of bacteria when prepared and remaining in a product itself are important factors for survival of the probiotics.^{[citation needed]} Dryness in a food product keeps the bacteria in a relatively quiescent state during storage, while a wet product establishes potentially active metabolism. Temperature affects shelf life of the bacteria, with low temperature providing conditions for possible long term survival.

Bacteria can respond to stressful environments by the induction of various stress tolerance mechanisms. One of them is the induction of stress proteins by exposure of the cells to sublethal stresses so they can condition probiotics to better tolerate environmental stresses in food production, storage, and gastrointestinal transit.^{[citation needed]} Different probiotic strains have their own intrinsic tolerances to environmental conditions,^{[citation needed]} including how the culture is prepared, and some cross-protection can be observed, providing protection against other stresses by the exposure to only one stress.^{[citation needed]} Stress responses can be explored to make probiotic strains more resilient and likely to survive in food matrices, with significant industrial importance.

Temperature

The temperature at which probiotic organisms grow is an important factor in food applications where fermentation is required, is also a critical factor influencing probiotic survival during manufacture and storage. As it is told above, the lower the temperature the more stable probiotic viability in the food product will be. During processing, temperatures over 45–50°C will be detrimental to probiotic survival, this means that the higher the temperature, the shorter the time period of exposure required to severely decrease the numbers of viable bacteria, ranging from hours or minutes at 45–55°C to seconds at higher temperatures. Therefore it is obvious that probiotics should be added downstream of heating/cooking/pasteurization processes in food manufacture to avoid the high temperatures. Elevated temperature also has a detrimental effect on stability during the product process of shipping and storage. Again, the cooler a product can be maintained, the better probiotic survival will be, like in vegetative probiotic cells in liquid products, where refrigerated storage is usually essential. If the product is dried, the bacteria will be in a quiescent state, so acceptable probiotic viability can be maintained in dry products stored at ambient temperatures for 12 months or more. Producing and maintaining low water activities in the foods is the key to maintaining probiotic viability during nonrefrigerated storage because there is a remarkable interaction between temperature and water activity.

pH

Some bacteria like Lactobacilli and bifidobacteria can tolerate lower pH levels because produce organic acid and products from carbohydrate metabolism. Indeed, numerous in vitro and in vivo studies have demonstrated that in gastric transit where the cells are exposed to low pH values and with a time of exposure relatively short, some probiotic organisms can survive. In fermented milks and yogurts with pH values between 3.7 and 4.3. lactobacilli are able to grow and survive, while Bifidobacteria tend to be less acid tolerant, with most species surviving poorly in fermented products at pH levels below 4.6. B. animales subsp. lactis is most commonly used in acidic foods because is more acid tolerant than human intestinal species, and B. thermoacidophilum, is even more tolerant to low pH (and heat), but has not yet been characterized thoroughly for probiotic traits and is not used commercially.

Regarding to fruit juices (pH 3.5–4.5) commercially successful products have been produced, such as Gefilus (Valio Ltd, Finland), which contains Lactobacillus rhamnosus GG. The viability at low pH can be improved with carriers such as dietary fibers. Survival of lactobacilli in low pHs has also been enhanced in the presence of metabolizable sugars, that allow cell membrane proton pumps to operate and prevent lowering of intracellular pH. This can improve survival during gastric transit, but may not be applicable to improving probiotic survival over the time stages of shelf-storage.

Water activity

For quiescent probiotic bacteria, water activity is a crucial determinant of survival in food products during storage. The higher moisture levels and water activity, the lower survival of probiotics. There is a substantial interaction between water activity and temperature with respect to their impact on the survival of quiescent probiotics. As the storage temperature is increased, the detrimental impact of moisture is magnified. Here, the osmotic stresses appear to play a role, with the presence of smaller molecules resulting in poorer bacterial survival, although the exact cell death mechanisms have not been elucidated yet.

There may be technological limitations to reducing water activity to low levels for improving survival. These include the energy costs of drying, adverse impacts on the taste of foods and difficulties in wetting and dispersing powders. Moisture barrier packaging may be applied to prevent the development of moisture from the environment during storage. Maintaining probiotic viability in moderate water activity foods (0.4–0.7) is a great challenge and solutions such as microencapsulation or incorporation of probiotics into fat phases of products can provide improved survival.

Oxygen

Both bifidobacteria and lactobacilli are considered strict anaerobes and oxygen can be detrimental to its growth and survival. However, the degree of oxygen sensitivity varies considerably between different species and strains, for example, lactobacilli, which are mostly microaerophilic, are more tolerant of oxygen than bifidobacteria, to the point where oxygen levels are not an important consideration in maintaining the survival of lactobacilli. Most probiotic bifidobacteria do not grow well in the presence of oxygen, although, many bifidobacteria have enzymatic mechanisms to limit the oxygen toxicity.

For oxygen sensitive strains, some strategies can be used to prevent oxygen toxicity in food products. Antioxidant ingredients have been shown to improve probiotic survival, as well as the use of oxygen barrier or modified-atmosphere packaging. Therefor, it is advisable to minimize processes that are highly aerating, particularly when using bifidobacteria.

Toxicity of ingredients

Interactions between probiotics and other ingredients could happen and those interactions can be protective, neutral, or detrimental to probiotic stability. Obviously, the inclusion of antimicrobial preservatives can inhibit probiotic survival and elevated levels of ingredients such as salt, organic acids, and nitrates can inhibit probiotics during storage, while starter cultures can sometimes inhibit the growth of probiotics during fermentation through the production of specific bacteriocins.

Growth factors, protective, and synergistic ingredients

Probiotic lactobacilli and, in particular, bifidobacteria are only weakly proteolytic and grow relatively slowly or poorly in milk. The growth of bifidobacteria can be improved by the presence of suitable companion cultures, which can aid in protein hydrolysis and through the production of growth factors. Some growth substrates such as carbon sources, nitrogen sources, and growth factors or antioxidants, minerals, and vitamins can be added to improve growth. Finally, the food matrix itself can be protective like in the cheese, where the anaerobic environment, high fat content and buffering capacity of the matrix helps to protect the probiotic cells both in the product and during intestinal transit.

Freeze–thawing

The damages made to cell membranes freezing probiotics is detrimental to survival, and also can make the cells more vulnerable to environmental stresses. To prevent or at least mitigate cell injury, protectants are usually added to cultures to be frozen or dried. Once frozen, probiotics can survive well over long shelf lives in products such as frozen yogurts and ice-cream. Using alternative methods of freezing, such as slow-cooling rates or pre-freezing stress, can significantly improve cell survival. Repeated freeze–thawing cycles are highly detrimental to cell survival and should be avoided.

Shear forces

Probiotic lactobacilli and bifidobacteria are Gram-positive bacteria with thick cell walls that are able to tolerate the shear forces generated in most standard food production processes such as high-speed blending or homogenization, that may result in cell disruption and losses in viability.^[56]

Side-effects

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.^[57]

In a clinical trial conducted at the University of Western Australia, 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 life. Those given the good bacteria were more likely to develop a sensitivity to allergens.^[58]

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.^[58][59]

There is no published evidence that probiotic supplements are able to replace the body's natural flora when these have been killed off; indeed bacterial levels in feces disappear within days when supplementation ceases.^[60]

Probiotics taken orally can be destroyed by the acidic conditions of the stomach. A number of micro-encapsulation techniques are being developed to address this problem.^[61]

Recent studies indicate that probiotic products such as yogurts could be a cause for obesity trends.^[62] However, this is contested as the link to obesity, and other health related issues with yogurt may link to its dairy and calorie attributes.^[63][64]

Some experts are skeptical on the efficacy of many strains and believe not all subjects will benefit from the use of probiotics.^[65]

Strains

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.

In the table below, only preliminary evidence exists for the health claims stated. Few of the strains presented have been sufficiently developed in basic and clinical research to warrant application for health claim status to a regulatory agency such as the Food and Drug Administration or Europfean Food Safety Authority.

Probiotic Research and Producer Information[66]
Strain	Brandname	Producer	Claimed potential effect in humans
Bacillus coagulans GBI-30, 6086	GanedenBC30	Ganeden Biotech	May improve abdominal pain and bloating in IBS patients.[67] May increase immune response to a viral challenge.[68]
Bifidobacterium LAFTI B94 Bifidobacterium sp	LAFTI B94	Institut Rosell-Lallemand	Protects against Salmonella typhimurium in mice. Uses prebiotics for improved colonization. Facilitates apoptotic response when used in combination with resistant starch in a colon cancer model. Reduces inflammation and incidence of diarrhea in an animal IBS model.[citation needed] Reduces allergic responses in an allergy model. May reduce the severity of H. pylori infection of the stomach mucosa.[citation needed] Inhibits pathogenic bacteria, including H. pylori, monocytogenes, E. coli, and Salmonella typhimurium.[citation needed] Adheres to human intestinal cells.[citation needed] Synthesizes folate from yogurts.[citation needed]
Lactobacillus acidophilus LAFTI L10 Lactobacillus acidophilus	LAFTI L10	Institut Rosell-Lallemand	Enhances clearance of Candida albicans by induction of an immune response. Reduces allergic responses in an animal allergy model. Protects against Listeria monocytogenes in the gastrointestinal tract of mice. Reduces the incidence of tumor formation and the size of intestinal tumors in rats. Reduces inflammation in an animal IBS model.[citation needed] Inhibits pathogenic bacteria, including H. pylori, monocytogenes, E. colim, and Salmonella typhimurium.[citation needed] Adheres to human intestinal cells.[citation needed] Produces antimicrobial substances like H202.[citation needed]
Lactobacillus casei LAFTI L26 Lactobacillus casei	LAFTI L26	Institut Rosell-Lallemand	Protects against Salmonella typhimurium in mice. Reduces inflammation in an IBS model. Reduces allergic responses in an allergy model. Reduces the severity of H. pylori infection of the stomach mucosa.[citation needed] Inhibits pathogenic bacteria, including H. pylori, monocytogenes, E. coli, and Salmonella typhimurium.[citation needed] Adheres to human intestinal cells.[citation needed]
Bifidobacterium animalis subsp. lactis BB-12	Probio-Tec Bifidobacterium BB-12	Chr. Hansen	Human studies have shown that BB-12 alone or in combination may have an effect on the gastrointestinal system.[69]
Bifidobacterium breve Yakult	Bifiene	Yakult	[citation needed]
Bifidobacterium infantis 35624	Align	Procter & Gamble	In one study, showed significant improvement for abdominal pain/discomfort, bloating/distention, and bowel movement difficulty.[70]
Bifidobacterium animalis subsp. lactis HN019 (DR10)	Howaru Bifido	Danisco	[citation needed]
Bifidobacterium longum BB536		Morinaga Milk Industry	[citation needed]
Escherichia coli M-17	ProBactrix	BioBalance	[citation needed]
Escherichia coli Nissle 1917	Mutaflor	Ardeypharm	[citation needed]
Lactobacillus acidophilus DDS-1		Nebraska Cultures
Lactobacillus acidophilus LA-5		Chr. Hansen	Limited human studies have shown that LA-5 may have a beneficial effect on gastrointestinal health.[citation needed]
Lactobacillus acidophilus NCFM		Danisco	Shown in one study to reduce the side effects of antibiotic therapy.[71]
Lactobacillus casei DN114-001 (Lactobacillus casei Immunitas(s)/Defensis)	Actimel/DanActive	Danone	[citation needed]
Lactobacillus casei 431		Chr. Hansen	Limited human studies have shown that L. casei 431 alone or in combinations may have a beneficial effect within gastrointestinal health[citation needed]
Lactobacillus casei F19	Cultura	Arla Foods	[citation needed]
Lactobacillus casei Shirota	Yakult	Yakult	[citation needed]
Lactobacillus paracasei St11 (or NCC2461)[72]	Lactobacillus fortis	Nestlé	[citation needed]
Lactobacillus johnsonii La1 (= Lactobacillus LC1, Lactobacillus johnsonii NCC533)		Nestlé	May reduce incidences of H pylori-caused gastritis and reduces inflammation [73]
Lactococcus lactis L1A		Norrmejerier	Immune stimulation, improves digestive health, reduces antibiotic-associated diarrhoea[74]
Lactobacillus plantarum 299v	GoodBelly / ProViva/ TuZen/ Bion Transit / ProbiMage	Probi	May improve symptoms of IBS; however, more research is required.[75]
Lactobacillus reuteri ATTC 55730 (Lactobacillus reuteri SD2112)		BioGaia	Diarrhea prevention and mitigation in children,[76][77] eradication of H. pylori infection,[78] amelioration of gingivitis,[79] general illness prevention in children[80] and adults.[81]
Lactobacillus reuteri Protectis (DSM 17938, daughter strain of ATCC 55730)[82]		BioGaia
Lactobacillus rhamnosus ATCC 53013 (Also strain number GG, discovered by Gorbach & Goldin)	LGG, Gefilus, Vifit and others	Valio	[citation needed]
Lactobacillus rhamnosus LB21	Verum	Norrmejerier	May cause immune stimulation, may improve digestive health, may reduce antibiotic-associated diarrhoea[74]
Saccharomyces boulardii	DiarSafe and others	Wren Laboratories and others	May protect against antibiotic-associated diarrhoea and infections of Clostridium difficile and other clostridial species; limited evidence shows it may help treat acute diarrhoea.[83][84]
tested as mixture: Lactobacillus rhamnosus GR-1 & Lactobacillus reuteri RC-14	Bion Flore Intime Jarrow Fem-Dophilus	Chr. Hansen	In one study, oral ingestion resulted in vaginal colonisation and prevention of vaginitis.[85]
tested as mixture: Lactobacillus acidophilus NCFM & Bifidobacterium bifidum BB-12	Florajen3	American Lifeline, Inc	Reduction of C. difficile–associated disease (CDAD)[86].
tested as mixture: Lactobacillus acidophilus CL1285 & Lactobacillus casei LBC80R	Bio-K+ CL1285	Bio-K+ International	May affect digestive health. [52] In vitro inhibition of Listeria monocytogenes and L. innocua, Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium.[87] Reduction of symptoms of lactose intolerance and immune stimulation.[88]
Lactobacillus plantarum HEAL 9 & Lactobacillus paracasei 8700:2	Bravo Friscus/ ProbiFrisk	Probi	Is under study for common cold infections.[89]
Lactobacillus reuteri Prodentis (L. reuteri DSM 17938 & ATCC PTA 5289)	GUM PerioBalance	BioGaia
Lactobacillus helveticus R0052 & Lactobacillus rhamnosus R0011	A'Biotica and others	Institut Rosell	[citation needed]
Lactobacillus casei var. rhamnosus MG001 & Lactobacillus acidophilus MG002 & Lactobacillus plantarum MG003 & Enterococcus faecium MG004	Symprove Probiotic	Symprove Ltd.	[citation needed]

Some additional forms of lactic acid bacteria include:

• Lactobacillus bulgaricus
• Streptococcus thermophilus
• Lactobacillus bifidus - became new genus Bifidobacterium

Some fermented products containing similar lactic acid bacteria include:

• Pickled vegetables^[90][91][92]
• Fermented bean paste such as tempeh,^[93] miso and doenjang
• Kefir^{[citation needed]}
• Buttermilk or Karnemelk
• Kimchi ^[91][94]
• Pao cai^{[citation needed]}
• Sauerkraut^[95]
• Soy sauce^[96]
• Zha cai^{[citation needed]}

EFSA opinions of probiotics

The European Food Safety Authority has so far rejected 260 claims^[97] on probiotics in Europe due to insufficient research and thus no conclusive proof. This includes:

• Lactobacillus paracasei LMG P 22043 does not decrease potentially pathogenic gastro-intestinal microorganisms or reduce gastro-intestinal discomfort.
• Lactobacillus johnsonii BFE 6128 . Immunity and skin claims all too general for consideration under the NHCR.
• Lactobacillus fermentum ME-3 not shown to decrease potentially pathogenic gastro-intestinal microorganisms.
• Lactobacillus plantarum BFE 1685. Immunity claim deemed too general for NHCR.
• Bifidobacterium longum BB536 does not improve bowel regularity; does not resist cedar pollen allergens; does not decrease pathogens.
• Bifidobacterium animalis ssp. lactis Bb-12 does not help maintain normal LDL-blood cholesterol; does not decrease pathogens or boost immunity.
• Lactobacillus plantarum 299v does not reduce flatulence and bloating or protect DNA, proteins and lipids from oxidative damage.
• Lactobacillus rhamnosus LB21 NCIMB 40564 does not help maintain individual intestinal microbiota in subjects receiving antibiotic treatment.

^[8]

Multi-probiotic

Research is emerging on the potential health benefits of multiple probiotic strains as a health supplement as opposed to a single strain.^[98][99] As the human gut may contain several hundred microbe species, one theory indicates that this diverse environment may benefit from consuming multiple probiotic strains, an effect that remains unproved.

Incomplete list of supplement products that contain more than one strain.

Company	Product	Strains	Strain Qty
EMD Canada Inc.	Multibionta	Lactobacillus gasseri PA16/8, Bifidobacterium bifidum MF20/5, Bifidobacterium longum SP07/3	3
OptiBac Probiotics	For daily wellbeing	Bifidobacterium longum Rosell-175, Lactococcus lactis Rosell-1058, Bifidobacterium breve Rosell-70, Lactobacillus rhamnosus Rosell-11, Lactobacillus acidophilus Rosell-52, Bifidobacterium bifidum rosell-71	6
Symprove Ltd. UK	Symprove Probiotic	Lactobacillus casei var. rhamnosus MG001, Lactobacillus acidophilus MG002, Lactobacillus plantarum MG003, Enterococcus faecium MG004	4
WN Pharmaceuticals Ltd. (Canada)	Webber Naturals Complete Probiotic	Lactobacillus casei (HA-108), Lactobacillus rhamnosus (HA111), Lactobacillus acidophilus (HA-122), Bifidobacterium longum (HA-135), Bifidobacterium breve (HA-129)	5

See also

• Prebiotic (nutrition)
• Synbiotics
• Fecal bacteriotherapy

References

1. ^ 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 (October 2001). "Health and Nutritional Properties of Probiotics in Food including Powder Milk with Live Lactic Acid Bacteria". Food and Agriculture Organization of the United Nations, World Health Organization. http://www.who.int/entity/foodsafety/publications/fs_management/en/probiotics.pdf. Retrieved 2009-11-04. 
2. ^ Hamilton-Miller, Professor J. M. T.; G. R. Gibson, W. Bruck. "Some insights into the derivation and early uses of the word 'probiotic'". British Journal of Nutrition 2003 (90): 845. doi:10.1079/BJN2003954. http://journals.cambridge.org/download.php?file=%2FBJN%2FBJN90_04%2FS0007114503001946a.pdf&code=a5bb6b0c0d0a37101d84a553e6b92ef1. Retrieved 19 November 2009. 
3. ^ ^{a b} Metchnikoff, E. 1907. Essais optimistes. Paris. The prolongation of life. Optimistic studies. Translated and edited by P. Chalmers Mitchell. London: Heinemann, 1907.
4. ^ Mach T (November 2006). "Clinical usefulness of probiotics in inflammatory bowel diseases". Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society 57 Suppl 9: 23–33. PMID 17242485. http://www.jpp.krakow.pl/journal/archive/1106_s9/pdf/23_1106_s9_article.pdf. 
5. ^ 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. 
6. ^ 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. 
7. ^ Vanderhoof JA (November 2008). "Probiotics in allergy management". Journal of Pediatric Gastroenterology and Nutrition 47 Suppl 2: S38–40. doi:10.1097/01.mpg.0000338810.74933.c1. PMID 18931598. 
8. ^ ^{a b} http://www.efsa.europa.eu/en/ndaclaims/ndaclaims13.htm
9. ^ Vaughan RB (July 1965). "The romantic rationalist: A study of Elie Metchnikoff". Medical History 9: 201–15. PMC 1033501. PMID 14321564. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1033501. 
10. ^ Tissier, H. 1900. Recherchers sur la flora intestinale normale et pathologique du nourisson. Thesis, University of Paris, Paris, France.
11. ^ Die antagonistische Behandlung chronischer Darmstörungen mit Colibakterien (1918). Med Klin 2: 29–30. 
12. ^ 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. doi:10.1073/pnas.6.12.704. PMC 1084701. PMID 16576567. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1084701. 
13. ^ Rettger, L.F., W.N. Levy, L. Weinstein, and J.E. Weiss. 1935. Lactobacillus acidophilus and its therapeutic application. Yale University Press, New Haven.
14. ^ 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. 
15. ^ Tannock GW (September 2003). "Probiotics: time for a dose of realism". Current Issues in Intestinal Microbiology 4 (2): 33–42. PMID 14503687. 
16. ^ Ljungh A, Wadstrom T (editors) (2009). Lactobacillus Molecular Biology: From Genomics to Probiotics. Caister Academic Press. ISBN 978-1-904455-41-7. 
17. ^ 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. http://jds.fass.org/cgi/pmidlookup?view=long&pmid=2111831. 
18. ^ 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. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5216a1.htm. 
19. ^ Allen SJ, Martinez EG, Gregorio GV, Dans LF (2010). Allen, Stephen J. ed. "Probiotics for treating acute infectious diarrhoea". Cochrane Database Syst Rev 11 (11): CD003048. doi:10.1002/14651858.CD003048.pub3. PMID 21069673. 
20. ^ "Does yogurt decrease acute diarrhoeal symptoms in children with acute gastroenteritis". http://www.bestbets.org/bets/bet.php?id=1000. 
21. ^ D'Souza AL, Rajkumar C, Cooke J, Bulpitt CJ (June 2002). "Probiotics in prevention of antibiotic associated diarrhoea: meta-analysis". BMJ 324 (7350): 1361. doi:10.1136/bmj.324.7350.1361. PMC 115209. PMID 12052801. http://bmj.com/cgi/pmidlookup?view=long&pmid=12052801. 
22. ^ Cremonini F, Di Caro S, Nista EC et al. (August 2002). "Meta-analysis: the effect of probiotic administration on antibiotic-associated diarrhoea". Aliment. Pharmacol. Ther. 16 (8): 1461–7. doi:10.1046/j.1365-2036.2002.01318.x. PMID 12182746. 
23. ^ Mcfarland LV. (2006 Apr). "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. 
24. ^ Szajewska H, Mrukowicz J. (2005-09-01). "Meta-analysis: non-pathogenic yeast Saccharomyces boulardii in the prevention of antibiotic-associated diarrhoea". Aliment Pharmacol Ther 22 (5): 365–72. doi:10.1111/j.1365-2036.2005.02624.x. PMID 16128673. 
25. ^ Szajewska H, Ruszczyński M, Radzikowski A. (2006 Sep). "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. 
26. ^ ^{a b} Sazawal S, Hiremath G, Dhingra U, Malik P, Deb S, Black RE. (2006 June). "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. 
27. ^ "Lactobacillus rhamnosus LGG". http://www.chr-hansen.com/campaign_sites/probiotics_for_human_health/our_probiotic_products/strains/lggr.html. 
28. ^ Doron SI, Hibberd PL, Gorbach SL. (2008 Jul). "Probiotics for prevention of antibiotic-associated diarrhea". J Clin Gastroenterol 42 (Suppl 2): S58–63. doi:10.1097/MCG.0b013e3181618ab7. PMID 18542041. 
29. ^ Surawicz CM. (2008 Jul). "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. 
30. ^ ^{a b c d} 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. http://jn.nutrition.org/cgi/pmidlookup?view=long&pmid=10721912. 
31. ^ Wollowski I, Rechkemmer G, Pool-Zobel BL (February 2001). "Protective role of probiotics and prebiotics in colon cancer". The American Journal of Clinical Nutrition 73 (2 Suppl): 451S–455S. PMID 11157356. http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=11157356. 
32. ^ ^{a b} Brady LJ, Gallaher DD, Busta FF (February 2000). "The role of probiotic cultures in the prevention of colon cancer". The Journal of Nutrition 130 (2S Suppl): 410S–414S. PMID 10721916. http://jn.nutrition.org/cgi/pmidlookup?view=long&pmid=10721916. 
33. ^ 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. PMID 11114681. 
34. ^ 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. 
35. ^ ^{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 207122. PMID 14557292. http://cmr.asm.org/cgi/pmidlookup?view=long&pmid=14557292. 
36. ^ ^{a b} Ouwehand AC, Salminen S, Isolauri E (August 2002). "Probiotics: an overview of beneficial effects". Antonie Van Leeuwenhoek 82 (1–4): 279–89. doi:10.1023/A:1020620607611. PMID 12369194. http://www.kluweronline.com/art.pdf?issn=0003-6072&volume=82&page=279. 
37. ^ Hatakka K, Savilahti E, Pönkä A et al. (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 32161. PMID 11387176. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=32161. 
38. ^ Näse L, Hatakka K, Savilahti E et al. (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. 
39. ^ University of Pennsylvania School of Medicine (February 3, 2010). "'Good' bacteria keep immune system primed to fight future infections". ScienceDaily. http://www.sciencedaily.com/releases/2010/01/100127095945.htm. Retrieved July 13, 2010. 
40. ^ 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. 
41. ^ 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. 
42. ^ Boyle RJ, Bath-Hextall FJ, Leonardi-Bee J, Murrell DF, Tang ML (2008). Boyle, Robert John. ed. "Probiotics for treating eczema". Cochrane Database Syst Rev (4): CD006135. doi:10.1002/14651858.CD006135.pub2. PMID 18843705. 
43. ^ 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. 
44. ^ Hitti, Miranda (April 25, 2006). "Probiotics May Help Stressed Gut". WebMD. http://www.webmd.com/content/article/121/114283.htm. Retrieved 2006-10-24. 
45. ^ Whorwell PJ, Altringer L, Morel J et al. (July 2006). "Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome". Am. J. Gastroenterol. 101 (7): 1581–90. doi:10.1111/j.1572-0241.2006.00734.x. PMID 16863564. 
46. ^ Niedzielin K, Kordecki H, Birkenfeld B (2001). "A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome". Eur J Gastroenterol Hepatol 13 (10): 1143–7. doi:10.1097/00042737-200110000-00004. PMID 11711768. 
47. ^ Guyonnet D, Chassany O, Ducrotte P et al. (2007). "Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind, controlled trial". Aliment. Pharmacol. Ther. 26 (3): 475–86. doi:10.1111/j.1365-2036.2007.03362.x. PMID 17635382. 
48. ^ Kruis, W; Fric, P; Pokrotnieks, J; Lukás, M; Fixa, B; Kascák, M; Kamm, MA; Weismueller, J et al. (November, 2004). "Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine". Gut 53 (11): 1617–23. doi:10.1136/gut.2003.037747. PMC 1774300. PMID 15479682. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1774300. 
49. ^ Marcos A, Wärnberg J, Nova E, Gómez S, Alvarez A, Alvarez R, Mateos JA, Cobo JM (2004). "The effect of milk fermented by yogurt cultures plus Lactobacillus casei DN-114001 on the immune response of subjects under academic examination stress". European Journal of Nutrition 43 (6): 381–389. doi:10.1007/s00394-004-0517-8. PMID 15309418. 
50. ^ Probiotics may protect against food poisoning
51. ^ Hickson M, D'Souza AL, Muthu N et al. (2007). "Use of probiotic Lactobacillus preparation to prevent diarrhea associated with antibiotics: randomised double blind placebo controlled trial". BMJ 335 (7610): 80. doi:10.1136/bmj.39231.599815.55. PMC 1914504. PMID 17604300. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1914504. 
52. ^ ^{a b} Beausoleil M, Fortier N, Guénette S et al. (November 2007). "Effect of a fermented milk combining Lactobacillus acidophilus Cl1285 and Lactobacillus casei in the prevention of antibiotic-associated diarrhea: a randomized, double-blind, placebo-controlled trial". Canadian Journal of Gastroenterology 21 (11): 732–6. PMC 2658588. PMID 18026577. http://www.pulsus.com/journals/abstract.jsp?sCurrPg=journal&jnlKy=2&atlKy=7643&isuKy=749&isArt=t. 
53. ^ Bravo, Javier et al. (August 29, 2011). "Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve". Proceedings of the National Academy of Sciences 108 (38): 16050–5. doi:10.1073/pnas.1102999108. PMC 3179073. PMID 21876150. http://www.pnas.org/content/early/2011/08/26/1102999108. Retrieved 2 September 2011. 
54. ^ Mayo, B; van Sinderen, D (editor) (2010). Bifidobacteria: Genomics and Molecular Aspects. Caister Academic Press. ISBN 978-1-904455-68-4. 
55. ^ Sonomoto, K; Yokota, A (editor) (2011). Lactic Acid Bacteria and Bifidobacteria: Current Progress in Advanced Research. Caister Academic Press. ISBN 978-1-904455-82-0. 
56. ^ "Incorporating Probiotics into Food". pg. 60-67. Ross Crittenden, in "Handbook of Probiotics and Prebiotics". Y. K. Lee and S. Salminen. 2nd Edition. Ed. Wiley. (2009)
57. ^ Besselink MG, van Santvoort HC, Buskens E et al. (February 2008). "Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial". Lancet 371 (9613): 651–9. doi:10.1016/S0140-6736(08)60207-X. PMID 18279948. 
58. ^ ^{a b} Bee, Peta (November 10, 2008). "Probiotics, Not so friendly after all". The Times (London). http://www.timesonline.co.uk/tol/life_and_style/health/features/article5109777.ece. 
59. ^ "So-called 'friendly' bacteria may be dangerous, according to new research - so which should you be taking?". Daily Mail. 29 January 2008. http://www.dailymail.co.uk/health/article-510978/So-called-friendly-bacteria-dangerous-according-new-research--taking.html. 
60. ^ "Gut Reactions programme 3". BBC. http://www.bbc.co.uk/radio4/science/gutreactions.shtml. 
61. ^ 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. http://www.jmb.or.kr/submission/Journal/020/JMB020-10-01_FDOC_1.pdf. 
62. ^ Raoult,Didier (September 2009). "Probiotics and obesity : a link ?". Nature 9 (9): 616. doi:10.1038/nrmicro2209. 
63. ^ Raoult, Didier (2009). "No link between probiotics and obesity? Author reply". Nature Reviews Microbiology 7 (12): 901. doi:10.1038/nrmicro2209-c3. http://www.isapp.net/docs/obesity_and_probiotics_isapp_response_to_raoult.pdf. 
64. ^ Ehrlich, SD (2009). "Probiotics - little evidence for a link to obesity". Nature reviews. Microbiology 7 (12): 901; author reply 901. doi:10.1038/nrmicro2209-c1. PMID 19915581. 
65. ^ Bee, Peta (November 10, 2008). "Probiotics, not so friendly after all?". The Times (London). http://www.timesonline.co.uk/tol/life_and_style/health/features/article5109777.ece. Retrieved 18 June 2010. 
66. ^ Sanders, ME (June 2007). "Probiotics, strains matter". . Functional foods & nutraceuticals magazine: 36–41. http://www.functionalingredientsmag.com/article/Formulations/probiotics-strains-matter.aspx. 
67. ^ Hun, Larysa MD, FAAP, L (2009). "Bacillus coagulans Significantly Improved Abdominal Pain and Bloating in Patients with IBS". Postgraduate Medicine 121 (2): 119–124. doi:10.3810/pgm.2009.03.1984. PMID 19332970. http://www.postgradmed.com/index.php?free=pgm_03_2009?article=1984. 
68. ^ Baron, Mira MD, M (2009). "A patented A Strain of Bacillus coagulans Increased Immune Response to Viral Challenge". Postgraduate Medicine 121 (2): 114–118. doi:10.3810/pgm.2009.03.1971. PMID 19332969. http://www.postgradmed.com/index.php?free=pgm_03_2009?article=1971. 
69. ^ http://www.chr-hansen.com/fileadmin/user_upload/_temp_/Selected_summaries_BB-12.pdf
70. ^ Brenner DM, Moeller MJ, Chey WD, Schoenfeld PS (April 2009). "The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review". The American Journal of Gastroenterology 104 (4): 1033–49; quiz 1050. doi:10.1038/ajg.2009.25. PMID 19277023. 
71. ^ Engelbrektson, A.; Korzenik, J. R.; Pittler, A.; Sanders, M. E.; Klaenhammer, T. R.; Leyer, G.; Kitts, C. L. (2009). "Probiotics to minimize the disruption of faecal microbiota in healthy subjects undergoing antibiotic therapy". Journal of Medical Microbiology 58 (5): 663–670. doi:10.1099/jmm.0.47615-0. 
72. ^ Sarker SA, Sultana S, Fuchs GJ, Alam, NH, Azim, T, Brüssow, H, Hammarström, L (August 2005). "Lactobacillus paracasei strain ST11 has no effect on rotavirus but ameliorates the outcome of nonrotavirus diarrhea in children from Bangladesh". Pediatrics 116 (2): e221–8. doi:10.1542/peds.2004-2334. PMID 15995003. 
73. ^ Sgouras, D. N.; Panayotopoulou, E. G.; Martinez-Gonzalez, B.; Petraki, K.; Michopoulos, S.; Mentis, A. (2005). "Lactobacillus johnsonii La1 Attenuates Helicobacter pylori-Associated Gastritis and Reduces Levels of Proinflammatory Chemokines in C57BL/6 Mice". Clinical and Vaccine Immunology 12 (12): 1378. doi:10.1128/CDLI.12.12.1378-1386.2005. 
74. ^ ^{a b} "Nyttiga bakterier bringar ordning i oroliga sommarmagar" (in Swedish). Norrmejerier. 2003-07-01. Archived from the original on 2007-10-10. http://web.archive.org/web/20071010234233/http://www.verum.se/default0.asp?varpresentdomain=www.verum.se&varpresenturl=/bib/nm.asp&varpresentqs=Documentkey%3dCA0C5F5F664AC396C1256DC7002BC66F%26DocumentCategoryKey%3dB716C33872CE35C5C1256DBF003D3EB9&redir=1. Retrieved 2007-08-25. 
75. ^ Niedzielin K, Kordecki H, Birkenfeld B. (October 2001). "A controlled, double-blind, randomized study on the efficacy of Lactobacillus plantarum 299V in patients with irritable bowel syndrome". Eur J Gastroenterol Hepatol. 13 (10): 1135–6. doi:10.1097/00042737-200110000-00004. PMID 11711768. 
76. ^ Ruiz-Palacios G, Guerrero ML, Hilty M. (1996). "Feeding of a probiotic for the prevention of community-acquired diarrhea in young Mexican children". Pediatr Res 39 (4): 184. http://www.noosit.com/02Prodotti/01reuterin/approfondimenti/02documenti/05-Feeding_of_a_probiotic_for_the_prevention_of_community.pdf. 
77. ^ Shornikova AV, Casas IA, Mykkänen H, Salo E, Vesikari T (December 1997). "Bacteriotherapy with Lactobacillus reuteri in rotavirus gastroenteritis". Pediatr. Infect. Dis. J. 16 (12): 1103–7. doi:10.1097/00006454-199712000-00002. PMID 9427453. 
78. ^ Saggioro A, Caroli M, Pasini M, Bortoluzzi F, Girardi L, Pilone G. (2005). "Helicobacter pylori eradication with Lactobacillus reuteri. A double blind placebo-controlled study". Dig Liver Dis 37 (suppl 1): S88, abstr. PO1.49. 
79. ^ Krasse P, Carlsson B, Dahl C, Paulsson A, Nilsson A, Sinkiewicz G (2006). "Decreased gum bleeding and reduced gingivitis by the probiotic Lactobacillus reuteri". Swed Dent J 30 (2): 55–60. PMID 16878680. 
80. ^ Weizman Z, Asli G, Alsheikh A (January 2005). "Effect of a probiotic infant formula on infections in child care centers: comparison of two probiotic agents". Pediatrics 115 (1): 5–9. doi:10.1542/peds.2004-1815 (inactive 2009-08-03). PMID 15629974. 
81. ^ Tubelius P, Stan V, Zachrisson A (2005). "Increasing work-place healthiness with the probiotic Lactobacillus reuteri: a randomised, double-blind placebo-controlled study". Environ Health 4: 25. doi:10.1186/1476-069X-4-25. PMC 1298318. PMID 16274475. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1298318. 
82. ^ Rosander A, Connolly E, Roos S. (Oct 2008). "Removal of antibiotic resistance gene-carrying plasmids from Lactobacillus reuteri ATCC 55730 and characterization of the resulting daughter strain, L. reuteri DSM 17938". Appl Environ Microbiol. 74 (19): 6032–40. doi:10.1128/AEM.00991-08. PMC 2565949. PMID 18689509. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2565949. 
83. ^ Hochter, W.. "Therapeutic evaluation of Saccharomyces boulardii in children with acute diarrhea" (PDF). Annales de Pediatrie 41 (6): 397–400. http://www.dtecta.co.uk/casestudies/Cetina_Sauri_&_Basto_(1994)_Therapeutic_Evaluation_of_Saccharomyces_boulardii_in_children_with_acute_diarrhoea_DiarSafe_DTECTA_Probiotics_www.dtecta.co.uk.pdf. 
84. ^ Kurugöl Z, Koturoğlu G (January 2005). "Effects of Saccharomyces boulardii in children with acute diarrhoea". Acta Paediatrica 94 (1): 44–7. doi:10.1080/08035250410022521. PMID 15858959. 
85. ^ Anukam K, Osazuwa E, Ahonkhai I, Ngwu, Michael, Osemene, Gibson, Bruce, Andrew W., Reid, Gregor (May 2006). "Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14: randomized, double-blind, placebo controlled trial". Microbes Infect. 8 (6): 1450–4. doi:10.1016/j.micinf.2006.01.003. PMID 16697231. 
86. ^ "Cdif Clinical Study". http://www.florajen.com/pdfs/CdifClinicalStudy.pdf. 
87. ^ Millette, M; Luquet, FM; Lacroix, M (March 2007). "In vitro growth control of selected pathogens by Lactobacillus acidophilus- and Lactobacillus casei-fermented milk". Letters of Applied Microbiology 44 (3): 314–9. doi:10.1111/j.1472-765X.2006.02060.x. PMID 17309510. 
88. ^ Robinson, R.K., ed (2007). "Sellars, R.L.". Acidophilus Products (Therapeutic Properties of Fermented Milks). Chapman & Hall, London. pp. 81–116. 
89. ^ Berggren A, Lazou Ahrén I, Larsson N, Onning G. (Aug 2010). "Randomised, double-blind and placebo-controlled study using new probiotic lactobacilli for strengthening the body immune defence against viral infections". Eur J Nutr. 50 (3): 203–10. doi:10.1007/s00394-010-0127-6. PMID 20803023. 
90. ^ Seseña, S; Palop, ML; M.Ll. Palop (2007). "An ecological study of lactic acid bacteria from Almagro eggplant fermentation brines". Journal of Applied Microbiology (Blackwell Publishing) 103 (5): 1553–1561. doi:10.1111/j.1365-2672.2007.03387.x. PMID 17953566. http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2672.2007.03387.x. Retrieved 7 November 2007. 
91. ^ ^{a b} Breidt, Jr, Frederick et al. (2007). "Fermented Vegetables" (PDF). ASM Press. http://fsweb2.schaub.ncsu.edu/USDAars/Acrobatpubs/P329-350/P345.pdf. Retrieved 7 November 2007. 
92. ^ Ji, Feng-Di; Ji, B.-P.; Li, B.; Han, B.-Z. (2007). "Note. Microbial Changes During the Salting Process of Traditional Pickled Chinese Cabbage". Food Science and Technology International (SAGE Publications) 13 (1): 11–16. doi:10.1177/1082013207075952. http://fst.sagepub.com/cgi/content/abstract/13/1/11. Retrieved 7 November 2007. 
93. ^ Moreno, M.R.F.; 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. http://www.blackwell-synergy.com/doi/abs/10.1046/j.1365-2672.2002.01509.x. Retrieved 7 November 2007. 
94. ^ 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. http://www.liebertonline.com/doi/abs/10.1089/109662004322984680?cookieSet=1&journalCode=jmf. Retrieved 7 November 2007. 
95. ^ Friedman, Y et al. (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. PMC 1463031. PMID 16710463. http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-34582006000400011&tlng=&lng=en&nrm=iso. Retrieved 7 November 2007. 
96. ^ Tanasupawat, Somboon et al. (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. http://www.jstage.jst.go.jp/article/jgam/48/4/201/_pdf. Retrieved 6 November 2007. 
97. ^ http://www.nutraingredients.com/Regulation/EFSA-calls-for-characterisation-work-as-probiotic-resubmissions-loom
98. ^ 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. 
99. ^ Williams E, Stimpson J, Wang D et al. (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

Books

• Hattner, J.A.T./Anderes, S. ”Gut Insight: probiotics and prebiotics for digestive health and well-being”, 2009, Hattner Nutrition. ISBN 9780578026152
• Huffnagle, G.B/Wernick, S. “The Probiotics Revolution: The Definitive Guide to Safe, Natural Health Solutions Using Probiotic and Prebiotic Foods and Supplements”, 2008, Bantam. ISBN 9780553384192
• Lipski, E. “Digestive Wellness: Strengthen the Immune System and Prevent Disease Through Healthy Digestion”, 2011 (4. ed.), Mc-Graw Hill. ISBN 9780071668996

Review articles

• De Preter, V. et al. ”The impact of pre- and/or probiotics on human colonic metabolism: Does it affect human health?”, Molecular Nutrition & Food Research (2011),55(1):46-57.
• Prakash, S. et al. “Gut microbiota: next frontier in understanding human health and development of biotherapeutics”, Biologics: Targets & Therapy (2011), 5:71-86.

External links

• International Scientific Association for Probiotics and Prebiotics
• Probiotics: Considerations for Human Health
• Getting To Know "Friendly Bacteria"
• Probiotics: Friendly Bacteria With a Host of Benefits
• International Food Information Council
• WhyFiles.org: Web magazine feature about probiotics
• Probiotic may ease fatigue syndrome anxiety