Probiotics are live microorganisms thought to be healthy for 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^[when?] 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]

[edit] History of probiotics

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.^[3] Metchnikoff, at that time a professor at the Pasteur Institute in Paris, produced the notion 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.^[8]

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 ^[9] 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.^[10] 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 ssp bulgaricus, could not live in the human intestine,^[11] and the fermented food phenomena 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.^[12] 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 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 which has been widely used: "A live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance".^[13] 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.^[14]

[edit] 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. Recent research on the molecular biology and genomics of Lactobacillus has focused on the interaction with the immune system, anti-cancer potential, and potential as a biotherapeutic agent in cases of antibiotic-associated diarrhoea, travellers' diarrhoea, pediatric diarrhoea, inflammatory bowel disease and irritable bowel syndrome.^[15]

All effects can only be attributed to the individual strain(s) tested. Testing of a supplement does not indicate benefit from any other strain of the same species, and testing does not indicate benefit from the whole group of LAB (or other probiotics).^[16]

[edit] 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.^[17]

[edit] Prevention of colon cancer

In laboratory investigations, some strains of LAB (Lactobacillus 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.^[18] Animal studies have demonstrated that some LAB can protect against colon cancer in rodents, though human data is limited and conflicting.^[19] Most human trials have found that the strains tested may exert anti-carcinogenic effects by decreasing the activity of an enzyme called β-glucuronidase^[19] (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.^[17]

[edit] Lowering cholesterol

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.^[17]

[edit] 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.^[17]

[edit] 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.^[20][21] Clinical trials have demonstrated that probiotics may decrease the incidence of respiratory tract infections^[22] and dental caries in children.^[23] LAB foods and supplements have been shown to be aid in the treatment and prevention of acute diarrhea, and in decreasing the severity and duration of rotavirus infections in children and travelers' diarrhea in adults.^[20][21]

[edit] 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. However more studies are required into this area.^[24]

[edit] Antibiotic-associated diarrhea

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 can reduce the incidence and severity of AAD as indicated in several meta-analyses.^{[25][26][27][28][28][29]} However, further documentation of these findings through randomized, double blind, placebo-controlled trials are warranted. Efficacy of probiotic AAD prevention is dependent on the probiotic strain(s) used and on the dosage.^[30][31] Up to a 50% reduction of AAD occurrence has been found.^[29] 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.

[edit] 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.^[20] Clinical studies suggest that they can prevent reoccurrences of inflammatory bowel disease in adults,^[20] as well as improve milk allergies.^[32] They are not effective for treating eczema, a persistent skin inflammation.^[33]. How probiotics counteract immune system overactivity remains unclear, but a potential mechanism is desensitization of so-called T lymphocytes, an important compenent of the immune system, towards pro-inflammatory stimuli ^[34].

[edit] 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.^[35]

[edit] Preventing 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.^[36]

[edit] 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.^[37] Another probiotic bacterium, Lactobacillus plantarum 299v, was also found to be effective in reducing IBS symptoms.^[38] Additionally, a probiotic formulation, VSL#3, was found to be safe in treating ulcerative colitis, though efficacy in the study was uncertain.^[39] Bifidobacterium animalis DN-173 010 may help.^[40]

[edit] Managing urogenital health

Several in vitro studies have revealed probiotics' potential in relieving urinary tract infections^[41] and bacterial vaginosis.^[42] Results have been varied on these studies, and in vivo studies are still required in this area to determine efficacy.

[edit] Potentially adverse effects

While the oral use of probiotics is considered safe and even recommended by the World Health Organization (WHO) under specific guidelines,^[1] in some specific situations (such as critically ill patients) they could be potentially harmful. In a therapeutic clinical trial conducted by M. Besselink and colleagues in The Netherlands, the consumption of a cocktail containing genetically modified strains of probiotic bacteria, increased the death rate of patients with acute pancreatitis^[43]. Probiotics have been shown to be beneficial for other types of patients^[44][45].

In a clinical trial conducted at the University of Western Australia, aimed at showing the effectiveness of probiotics in reducing childhood allergies, Dr Susan Prescott and her colleagues gave 178 children either a probiotic or a placebo for the first six months of their life, those given the good bacteria were more, not less, likely to develop a sensitivity to allergens.^[46]

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.^[46][47]

[edit] 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.

Some other bacteria mentioned in probiotic products: (yoghurt bacteria):

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

Some fermented products containing similar lactic acid bacteria include:

• Pickled vegetables^[68][69][70]
• Fermented bean paste such as tempeh,^[71] miso and doenjang
• Kefir^{[citation needed]}
• Buttermil or Karnemelk
• Kimchi ^[69][72]
• Kombucha^{[citation needed]}
• Pao cai^{[citation needed]}
• Sauerkraut^[73]
• Soy sauce^[74]
• Zha cai^{[citation needed]}

[edit] Multi-probiotic

Research is emerging on the potential health benefits of multiple probiotic strains as a health supplement as opposed to a single strain.^[75][76] The human gut is home to some 400-500 types of microbes. It is thought that this diverse environment may benefit from multiple probiotic strains; different strains populate different areas of the digestive tract, and studies are beginning to link different probiotic strains to specific health benefits.

Supplement products that contain more than one probiotic strain:

[edit] Synbiotics

As probiotics are mainly active in the small intestine and prebiotics are only effective in the large intestine,^[77] the combination of the two may give a synergistic effect. Appropriate combinations of pre- and probiotics are synbiotics.

[edit] Research

Research about probiotics shows both harm^[where?] and benefits.

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 probiotics have no overall effect on the immune system or on its ability.^[78]

A 2007 study at University College Cork in Ireland showed that a diet including milk fermented with Lactobacillus bacteria prevented Salmonella infection in pigs.^[79]

A 2007 clinical study at Imperial College London showed that preventive consumption of a commercially available probiotic drink containing L casei DN-114001, L bulgaricus, and S thermophilus can reduce the incidence of antibiotic-associated diarrhea and C difficile-associated diarrhea.^[80]

The efficacy and safety of a daily dose of Lactobacillus acidophilus CL1285 in the prevention of AAD was demonstrated by Montreal’s Maisonneuve-Rosemont Hospital, in a clinical study of hospitalized patients.^[65]

[edit] Criticisms

Some experts are skeptical on the efficacy of many strains and believe not all subjects will benefit from the use of probiotics.^[81] A criticism of probiotic supplements^{[by whom?]} is the cost and value of probiotics products.^[81]

[edit] See also

• Prebiotic (nutrition)

[edit] References

[edit] External links

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