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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Overview

Probiotics are dietary supplements containing potentially beneficial bacteria or yeasts. 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) are the most common type of microbes used. LAB have been used in the food industry for many years, because they are able to convert sugars (including lactose) and other carbohydrates into lactic acid. This not only provides the characteristic sour taste of fermented dairy foods such as yogurt, but acts as a preservative, by lowering the pH and creating fewer opportunities for spoilage organisms to grow. Strains of the genera Lactobacillus and Bifidobacterium, are the most widely used probiotic bacteria. [2]

Probiotic bacterial cultures are intended to assist the body's naturally occurring gut flora to reestablish themselves. They are sometimes recommended by doctors, and, more frequently, by nutritionists, after a course of antibiotics, or as part of the treatment for gut related candidiasis. Claims are made that probiotics strengthen the immune system. [3]

The rationale for probiotics is that the body contains a miniature ecology of microbes, collectively known as the gut flora. A number of bacterial types are thought to be thrown out of balance by a wide range of circumstances including the use of antibiotics or other drugs, excess alcohol, stress, disease, or exposure to toxic substances. In cases like these, the bacteria that work well with our bodies (see symbiosis) may decrease in number, an event which allows harmful competitors to thrive, to the detriment of our health.

Maintenance of a healthy gut flora is, however, dependent on many factors, especially the quality of food intake. Including a significant proportion of prebiotic foods in the diet has been demonstrated <needs reference> to support a healthy gut flora and may be another means of achieving the desirable health benefits promised by probiotics.

History of probiotics

Probiotics, which means "for life", have been used for centuries as natural components in health-promoting foods. The original observation of the positive role played by certain bacteria was first introduced by Russian scientist and Nobel laureate Eli 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 by useful microbes. [4] Metchnikoff, at that time a professor at the Pasteur Institute in Paris, produced the notion that the ageing 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 LAB 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 LAB were exceptionally long lived. Based on these facts, Metchnikoff proposed that consumption of fermented milk would “seed” the intestine with harmless LAB 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.[5]
Henry Tissier, also from the Pasteur Institute, was the first to isolate a Bifidobacterium. He isolated the bacterium from a breast-fed infant and named it Bacillus bifidus communis.[6] This bacterium was later renamed Bifidobacterium bifidum. Tissier showed that bifidobacteria are predominant in the gut flora of breast-fed babies, and he recommended administration of bifidobacteria to infants suffering from diarrhea. The mechanism claimed, was that bifidobacteria would displace the proteolytic bacteria that cause the disease.
German professor Alfred Nissle, in 1917 isolated a strain of Escherichia coli from the feces of a First World War soldier who did not develop enterocolitis during a severe outbreak of shigellosis.[7] In those days, antibiotics were not yet discovered, and Nissle used the strain with considerable success in acute cases of infectious intestinal diseases (salmonellalosis and shigellosis). Escherichia coli Nissle 1917 is still in use and is one of the few examples of a non-LAB probiotic.
In 1920 Rettger demonstrated that Metchnikoff’s “Bulgarian Bacillus”, later called Lactobacillus bulgaricus, could not live in the human intestine[8], and the fermented food phenomena pitted 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 USA. 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.[9] 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 1965 by Lilly and Stillwell, when it was described as growth promoting factors produced by microorganisms (protozoa).[10]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 which has been widely used: “A live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance”.[11] Fuller’s definition emphasizes the requirement of viability for probiotics and introduces the aspect of a beneficial effect on the host.
In the 1960s the dairy industry began to promote new yoghurts containing Lactobacillus acidophilus. In the subsequent decades other Lactobacillus species have been introduced including Lactobacillus rhamnosus, Lactobacillus casei, and Lactobacillus johnsonii, because they are intestinal species with beneficial properties.[12]

Effects

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[13]. It is hoped, however, that probiotics do form beneficial temporary colonies which may assist the body in the same functions as the natural flora, while allowing the natural flora time to recover from depletion. The probiotic strains are then thought to be progressively replaced by a naturally developed gut flora. Hence, probiotics have been defined as correctives of the ecoorgan. If the conditions which originally caused damage to the natural gut flora persist, the benefits obtained from probiotic supplements will be short lived.

Potential benefits

Experiments into the benefits of probiotic therapies suggest a range of potentially beneficial medicinal uses for probiotics. For many of the potential benefits, research is limited and only preliminary results are available. It should be noted that the effects described are not general effects of probiotics. All effects can only be attributed to the strain(s) tested, not to the species, nor to the whole group of LAB (or other probiotics).

Managing 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 what they would have otherwise.[3] In practice probiotics are not specifically targeted for this purpose, as most are relatively low in lactase activity as compared to the normal yogurt bacteria.

Prevention of Colon Cancer

In laboratory investigations, some strains of LAB have demonstrated anti-mutagenic effects thought to be due to their ability to bind with heterocyclic amines; carcinogenic substances formed in cooked meat.[14] Animal studies have demonstrated that some LAB can protect against colon cancer in rodents, though human data is limited and conflicting.[15] Most human trials have found that the strains tested may exert anti-carcinogenic effects by decreasing the activity of an enzyme called ß-glucuronidase[15] (which can generate carcinogens in the digestive system). Lower rates of colon cancer among higher consumers of fermented dairy products have been observed in some population studies.[3]

Cholesterol Lowering

Animal studies have demonstrated the efficacy of a range 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). Some, but not all human trials have shown that dairy foods fermented with specific LAB can produce modest reductions in total and LDL cholesterol levels in those with normal levels to begin with, however trials in hyperlipidemic subjects are needed.[3]

Lowering Blood Pressure

Several small clinical trials have shown that consumption of milk fermented with various strains of LAB can result in modest reductions in blood pressure. It is thought that this is due to the ACE inhibitor-like peptides produced during fermentation.[3]

Improving Immune Function and Preventing Infections

LAB are thought to have several presumably beneficial effects on immune function. They may protect against 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.[16][17] Clinical trials have demonstrated that probiotics may decrease the incidence of respiratory tract infections[18] and dental caries in children[19] LAB foods and supplements have been shown to be effective in the treatment and prevention of acute diarrhea; decreasing the severity and duration of rotavirus infections in children as well as travelers diarrhea in adults.[16][17]

Helicobacter pylori

LAB are also thought to aid in the treatment of Helicobacter pylori infections (which cause peptic ulcers) in adults when used in combination with standard medical treatments.[20]

Antibiotic-associated diarrhea

A meta-analysis suggested probiotics may reduce antibiotic-associated diarrhea. [21] A subsequent randomized controlled trail also found benefit in elderly patients. [22]

Reducing Inflammation

LAB foods and supplements have been found to modulate inflammatory and hypersensitivity responses, an observation thought to be at least in part due to the regulation of cytokine function.[16] Clinical studies suggest that they can prevent reoccurrences of inflammatory bowel disease in adults,[16] as well as improve milk allergies[23] and decrease the risk of atopic eczema in children.[24]

Improving Mineral Absorption

It is hypothesized that probiotic lactobacilli may help correct malabsorption of trace minerals, found particularly in those with diets high in phytate content from whole grains, nuts, and legumes.[25]

Prevents Harmful 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.[26]

Irritable Bowel Syndrome and Colitis

B. infantis 35624, sold as Align, was found to improve some symptoms of irritable bowel syndrome in women in a recent study.[27] Another probiotic bacterium, Lactobacillus plantarum 299V, was also found to be effective in reducing IBS symptoms. [28] Additionally, a probiotic formulation, VSL3, was found to be effective in treating ulcerative colitis [29] Bifidobacterium animalis DN-173 010 may help. [30]

Synbiotics

It is also possible to increase and maintain a healthy bacterial gut flora by increasing the amounts of prebiotics in the diet such as inulin, raw oats, and unrefined wheat.

As probiotics are mainly active in the small intestine and prebiotics are only effective in the large intestine [31], the combination of the two may give a synergistic effect. Appropriate combinations of pre- and probiotics are synbiotics.

Synbiotics have also been defined as metabolites produced by ecoorgan or by synergistic action of prebiotics and probiotics e.g. short chain fatty acids, other fatty acids, amino acids, peptides, polyamines, carbohydrates, vitamins, numerous antioxidants and phytosterols, growth factors, coagulation factors, various signal molecules such as cytokine-like bacteriokines.

Types

The most common form for probiotics are dairy products and probiotic fortified foods. However, tablets and capsules containing the bacteria in freeze dried form are also available.

Proven probiotic strains. Source:[32]
Strain Brandname Producer Proven effect in humans
Lactobacillus rhamnosus ATCC 53013 (discovered by Gorbach & Goldin(=LGG)) Vifit and others Valio Immune stimulation, prevents diarrhoea in children and many other types of diarrhoea
Bifidobacterium animalis subsp. lactis BB-12 Chr. Hansen Immune stimulation, prevents diarrhoea in children
Bifidobacterium lactis HN019 (DR10) Howaru™ Bifido Danisco Immune stimulation
Bifidobacterium infantis 35624 Irritable Bowel Syndroom (IBS)
Bifidobacterium breve Yakult Bifiene Yakult
Lactobacillus reuteri ATTC 55730 BioGaia Biologics
Lactobacillus reuteri SD2112 Immune stimulation, against diarrhoea
Lactobacillus casei DN114-001 Immune stimulation
Lactobacillus casei CRL431 Chr. Hansen
Lactobacillus casei Shirota Yakult Yakult Immune stimulation
Lactobacillus casei immunitass Actimel Danone
Lactobacillus johnsonnii La1 (= Lactobacillus LC1) Nestlé Immune stimulation, active against Helicobacter pylori
Bifidobacterium longum BB536 positive effects against allergies
Lactobacillus salivarius UCC118 positive effects with intestinal ulcers and inflammation
Lactobacillus acidophilus NCFM Rhodia Inc. reduces symptoms of lactose intolerance, prevents bacterial overgrowth in small intestine
Lactobacillus plantarum 299V IBS, used post-operative
Lactobacillus acidophilus LA-5 Chr. Hansen
Bifidobacterium animalis DN 173 010 Activia Danone Stabilises intestinal passage
Escherichia coli Nissle 1917 Immune stimulation
Saccharomyces cerevisiae (boulardii) lyo against antibiotic-associated diarrhoea and Clostridium difficile infections
Streptococcus salivarius ssp thermophilus reduces symptoms of lactose intolerance
tested as mixture:
Lactobacillus rhamnosus GR-1 & Lactobacillus reuteri RC-14
Oral ingestion results in vaginal colonisation and prevention of vaginitis
tested as mixture:
VSL#3 (mixture of 8 srains of Streptococcus thermophilus & four Lactobacillus spp & three Bifidobacterium spp strains
positive effects with intestinal ulcers and inflammation
tested as mixture:
Lactobacillus acidophilus CUL60 & Bifidobacterium bifidum CUL 20
reduction of Cl. difficile in faeces
tested as mixture:
Lactobacillus helveticus R0052 & Lactobacillus rhamnosus R0011
prevents diarrhoea in children, active against Helicobacter pylori


Some commonly used bacteria in products, but without probiotic effect (yogurt bacteria):

Some other bacteria mentioned in probiotic products:

Some fermented products containing similar (often not proven to have a probiotic or health effect) lactic acid bacteria include:

Research

A 2007 study at University College Cork in Ireland showed that a diet including milk fermented with Lactobacillus bacteria prevented Salmonella infection in pigs.[33]

A 2007 clinical study at Imperial College London showed that consumption of a probiotic drink containing L casei, L bulgaricus, and S thermophilus can reduce the incidence of antibiotic associated diarrhoea and C difficile associated diarrhoea.[22]

Criticism

Some mainstream researchers in Europe as well as in the United States are skeptical of some of the claims made for probiotics. Their reasons include the following considerations[34]:

  • The studies done in support of probiotics are mostly anecdotal or heavily reliant on test-tube experimentation rather than on clinical trials in human subjects
  • The basic concept of probiotics is based on a misunderstanding of the role of microflora in the human digestive tract.
  • It is difficult to see how bacteria taken by mouth can survive the process of human digestion (though research shows that they do, in fact, survive [35])

References

  1. FAO/WHO (2001) Health and Nutritional Properties of Probiotics in Food including Powder Milk with Live Lactic Acid Bacteria. 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.
  2. Tannock G (editor). (2005). Probiotics and Prebiotics: Scientific Aspects (1st ed. ed.). Caister Academic Press. ISBN 978-1-904455-01-8 .
  3. 3.0 3.1 3.2 3.3 3.4 Sanders ME. Considerations for use of probiotic bacteria to modulate human health. J Nutr. 2000;130:384S-390S. Entrez PubMed 10721912
  4. Metchnikoff, E. 1907. Essais optimistes. Paris. The prolongation of life. Optimistic studies. Translated and edited by P. Chalmers Mitchell. London: Heinemann, 1907.
  5. Vaughan RB. 1965. The romantic rationalist: A study of Elie Metchnikoff. Med Hist. 9:201-15.
  6. Tissier, H. 1900. Recherchers sur la flora intestinale normale et pathologique du nourisson. Thesis, University of Paris, Paris, France.
  7. Nissle, A. 1918. Die antagonistische Behandlung chronischer Darmstörungen mit Colibakterien. Med Klin 1918, 2:29-30.
  8. Cheplin, H.A., and L.F. Rettger, 1920. Studies on the transformation of the intestinal flora, with special reference to the implantation of Bacillus acidophilus, II. Feeding experiments of man. Proc Natl Acad Sci U S A. 1920 December; 6(12): 704–705.
  9. Rettger, L.F., W.N. Levy, L. Weinstein, and J.E. Weiss. 1935. Lactobacillus acidophilus and its therapeutic application. Yale University Press, New Haven.
  10. Lilly, D.M, and R.H. Stillwell. 1065. Probiotics: growth-promoting factors produced by microorgansism. Science 147:747-748.
  11. Fuller, R. 1989. Probiotics in man and animals. J. Appl. Bacteroil. 66:365-378.
  12. Tannock, G.W. 2003. Probiotics: Time for a dose of realism. Curr. Intest. Microbiol. 4:33-42.
  13. Gut Reactions programme 3
  14. Wollowski I, Rechkemmer G, Pool-Zobel BL. Protective role of probiotics and prebiotics in colon cancer. Am J Clin Nutr. 2001;73:451S-455S. Entrez PubMed 11157356
  15. 15.0 15.1 Brady LJ, Gallaher DD, Busta FF. The role of probiotic cultures in the prevention of colon cancer. J Nutr. 2000;130:410S-414S. Entrez PubMed 10721916
  16. 16.0 16.1 16.2 16.3 Reid G, Jass J, Sebulsky MT, McCormick JK. Potential uses of probiotics in clinical practice. Clin Microbiol Rev. 2003;16:658-72. Entrez PubMed 14557292
  17. 17.0 17.1 Ouwehand AC, Salminen S, Isolauri E. Probiotics: an overview of beneficial effects. Antonie Van Leeuwenhoek. 2002;82:279-89. Entrez PubMed 12369194
  18. Hatakka K, Savilahti E, Ponka A, Meurman JH, Poussa T, Nase L, Saxelin M, Korpela R. Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. BMJ. 2001;322:1327 Entrez PubMed 11387176
  19. Nase L, Hatakka K, Savilahti E, Saxelin M, Ponka A, Poussa T, Korpela R, Meurman JH. Effect of long-term consumption of a probiotic bacterium, Lactobacillus rhamnosus GG, in milk on dental caries and caries risk in children. Caries Res. 2001;35:412-20. Entrez PubMed 11799281
  20. Hamilton-Miller JM. The role of probiotics in the treatment and prevention of Helicobacter pylori infection. Int J Antimicrob Agents. 2003;22:360-366. Entrez PubMed 14522098
  21. Cremonini F, Di Caro S, Nista EC, Bartolozzi F, Capelli G, Gasbarrini G, Gasbarrini A. Meta-analysis: the effect of probiotic administration on antibiotic-associated diarrhoea. Aliment Pharmacol Ther. 2002;16:1461-1467 Entrez PubMed 12182746
  22. 22.0 22.1 Hickson M, D'Souza AL, Muthu N; et al. (2007). "Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial". BMJ. 335 (7610): 80. doi:10.1136/bmj.39231.599815.55. PMID 17604300.
  23. Kirjavainen PV, Salminen SJ, Isolauri E Probiotic bacteria in the management of atopic disease: underscoring the importance of viability. J Pediatr Gastroenterol Nutr. 2003;36:223-227 Entrez PubMed 12548058
  24. Kalliomaki M, Salminen S, Poussa T, Arvilommi H, Isolauri E. Probiotics and prevention of atopic disease: 4-year follow-up of a randomised placebo-controlled trial. Lancet. 2003;361:1869-1871. Entrez PubMed 12788576
  25. Famularo G, De Simone C, Pandey V, Sahu AR, Minisola G. Probiotic lactobacilli: an innovative tool to correct the malabsorption syndrome of vegetarians? Med Hypotheses. 2005;65(6):1132-5. Entrez PubMed 16095846
  26. Hitti, Miranda (April 25, 2006). "Probiotics May Help Stressed Gut". WebMD. Retrieved 2006-10-24. Check date values in: |date= (help)
  27. Whorwell PJ, Altringer L, Morel J, Bond Y, Charbonneau D, O'Mahony L, Kiely B, Shanahan F, Quigley EM. (July, 2006). "Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome". Am J Gastroenterol. Retrieved 2006-12-6. Check date values in: |accessdate=, |date= (help)
  28. 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. PMID.
  29. Kerr, Martha (May 21, 2003). "Probiotics Significantly Reduce Symptoms of IBS, Ulcerative Colitis". Retrieved 2006-12-6. Check date values in: |accessdate=, |date= (help)
  30. 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.
  31. Glenn R. Gibson and Marcel B. Roberfroid ; Dietary Modulation of the Human Colonic Microbiota: Introducing the Concept of Prebiotics. Journal of Nutrition Vol. 125 No. 6 June 1995, pp. 1401-1412.
  32. Sanders ME. Probiotics, strains matter. Functional foods & nutraceuticals magazine (2007); June; pp. 36-41
  33. Probiotics may protect against food poisoning
  34. Gale, Thomas (2006). ""Probiotics." Encyclopedia of Alternative Medicine, eNotes.com". Retrieved 2007-29-1. Check date values in: |accessdate=, |date= (help)
  35. "Survival of Yogurt Bacteria in the Human Gut" Marina Elli et al. Appl Environ Microbiol 2006 July; 72(7): 5113–5117

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