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Probiotics

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Probiotics are dietary supplements of 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 also certain yeasts and bacilli are available.

At first, probiotics were thought to beneficially affect the host by improving its intestinal microbial balance, thus inhibiting pathogens and toxin producing bacteria. Today specific health effects are being investigated and documented including alleviation of chronic intestinal inflammatory diseases [2], prevention and treatment of pathogen-induced diarrhea [3], urogenital infections [4], and atopic diseases[5].

Contents

History of probiotics

Probiotics, which means, "for life," have been used for centuries as natural components in health-promoting foods.[citation needed] 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.[6] 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.[7]

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.[8] 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 faeces of a World War I soldier who did not develop enterocolitis during a severe outbreak of shigellosis.[9] In those days, antibiotics were not yet discovered, and Nissle used the strain with considerable success in acute cases of infectious intestinal diseases (salmonellosis 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,[10] 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 US. 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.[11] 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".[12] Fuller's definition emphasizes the requirement of viability for probiotics and introduces the aspect of a beneficial effect on the host.

In subsequent decades other Lactobacillus species have been introduced including Lactobacillus rhamnosus, Lactobacillus casei, and Lactobacillus johnsonii, because they are intestinal species with beneficial properties.[13]

Adverse effects

There is no published evidence that probiotic supplements are able to completely replace the body’s natural flora when these have been killed off; indeed bacterial levels in feces disappear within days when supplementation ceases.[14] While the oral use of probiotics is considered safe and even recommended by World Health Organization under specific guidelines [2], 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[15]. Probiotics have been shown to be beneficial for other types of patients[16][17].

In a clinical trial conducted at the University of Western Australia, aimed at showing the effectiveness of probiotics in reducting 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.[18]

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.[18][19]

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.[20]

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).[21]

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.[22] 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 (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.[23] Animal studies have demonstrated that some LAB can protect against colon cancer in rodents, though human data is limited and conflicting.[24] Most human trials have found that the strains tested may exert anti-carcinogenic effects by decreasing the activity of an enzyme called β-glucuronidase[24] (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.[22]

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.[22]

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.[22]

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.[25][26] Clinical trials have demonstrated that probiotics may decrease the incidence of respiratory tract infections[27] and dental caries in children.[28] 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.[25][26]

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.[29]

Antibiotic-associated diarrhea

A meta-analysis suggested probiotics may reduce antibiotic-associated diarrhea.[30] A subsequent randomized controlled trial also found benefit in elderly patients.[31]

In a randomized clinical trial, published in 2007, a University of Montreal team of pharmacologists demonstrated that lactobacilli-fermented solution can be effective in AAD prevention in hospitalized patients”.[32]

In 2009 Encap Drug Delivery announced that they had entered into a collaboration with Probac AB to develop a novel probiotic capsule product aimed at treating antibiotic associated diarrhoea.

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.[25] Clinical studies suggest that they can prevent reoccurrences of inflammatory bowel disease in adults,[25] as well as improve milk allergies.[33] They are not effective for treating eczema, a persistent skin inflammation.[34]. 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 [35].

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.[36]

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.[37]

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.[38] Another probiotic bacterium, Lactobacillus plantarum 299v, was also found to be effective in reducing IBS symptoms.[39] Additionally, a probiotic formulation, VSL#3, was found to be safe in treating ulcerative colitis, though efficacy in the study was uncertain.[40] Bifidobacterium animalis DN-173 010 may help.[41]

Managing urogenital health

Several in vitro studies have revealed probiotics' potential in relieving urinary tract infections[42] and bacterial vaginosis.[43] Results have been varied on these studies, and in vivo studies are still required in this area to determine efficacy.

Synbiotics

As probiotics are mainly active in the small intestine and prebiotics are only effective in the large intestine,[44] the combination of the two may give a synergistic effect. Appropriate combinations of pre- and probiotics are synbiotics.

Strains

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

Proven probiotic strains. Sources:[45] and [46]
Strain Brandname Producer Proven effect in humans
Bacillus coagulans GBI-30, 6086 GanedenBC30 Ganeden Biotech Improves abdominal pain and bloating in IBS patients.[47] Increases immune response to viral challenge.[48]
Bifidobacterium animalis subsp. lactis BB-12   Chr. Hansen [citation needed]
Bifidobacterium breve Yakult Bifiene Yakult [citation needed]
Bifidobacterium infantis 35624 Align Procter & Gamble [citation needed]
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[49] [citation needed]
Lactobacillus acidophilus LA-5   Chr. Hansen [citation needed]
Lactobacillus acidophilus NCFM   Danisco [citation needed]
Lactobacillus casei DN114-001 (Lactobacillus casei Immunitas(s)/Defensis) Actimel/DanActive Danone [citation needed]
Lactobacillus casei CRL431   Chr. Hansen [citation needed]
Lactobacillus casei F19 Cultura Arla Foods [citation needed]
Lactobacillus casei Shirota Yakult Yakult [citation needed]
Lactobacillus paracasei St11 (or NCC2461)[50] Lactobacillus fortis Nestlé  
Lactobacillus johnsonii La1 (= Lactobacillus LC1, Lactobacillus johnsonii NCC533)   Nestlé [citation needed]
Lactococcus lactis L1A   Norrmejerier Immune stimulation, improves digestive health, reduces antibiotic-associated diarrhoea[51]
Lactobacillus plantarum 299V GoodBelly / ProViva/ TuZen NextFoods Probi Ferring [citation needed]
Lactobacillus reuteri ATTC 55730 (Lactobacillus reuteri SD2112)   BioGaia Biologics Diarrhea prevention and mitigation in children[52][53], eradication of H. pylori infection[54], amelioration of gingivitis[55], general illness prevention in children[56] and adults[57].
Lactobacillus rhamnosus ATCC 53013 (discovered by Gorbach & Goldin(=LGG)) Vifit and others Valio [citation needed]
Lactobacillus rhamnosus LB21 Verum Norrmejerier Immune stimulation, improves digestive health, reduces antibiotic-associated diarrhoea[51]
Saccharomyces cerevisiae (boulardii) lyo DiarSafe and others Wren Laboratories and others against antibiotic-associated diarrhoea and Clostridium_difficile (cmd-click)">Clostridium_difficile (cmd-click)">[[Clostridium difficile]] infections; to treat acute diarrhoea in adults & children.[58].[59].[60]
tested as mixture:
Lactobacillus rhamnosus GR-1 & Lactobacillus reuteri RC-14		 Bion Flore Intime Jarrow Fem-Dophilus Chr. Hansen Oral ingestion results in vaginal colonisation and prevention of vaginitis

[61]
tested as mixture:
Lactobacillus acidophilus NCFM & Bifidobacterium bifidum BB-12		 Florajen3 American Lifeline, Inc Reduction of C. difficile–associated disease (CDAD)[3].
tested as mixture:
Lactobacillus acidophilus CL1285 & Lactobacillus casei		 Bio-K+ CL1285 Bio-K+ International Improves digestive health. Prevents Antiobic Associated Diarrhea (AAD) and Clostridium Difficile (C Difficile).[32]

In vitro inhibition of Listeria monocytogenes and L. innocua, Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium.[62]
Reduction of symptoms of lactose intolerance and immune stimulation.[63]
Lactobacillus helveticus R0052 & Lactobacillus rhamnosus R0011 A'Biotica and others Institut Rosell [citation needed]

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

  • Lactobacillus bulgaricus
  • Streptococcus thermophilus

Some other bacteria mentioned in probiotic products:

  • Lactobacillus bifidus - became new genus Bifidobacterium

Some fermented products containing similar lactic acid bacteria include:

  • Pickled vegetables[64], [65], [66]
  • Fermented bean paste such as tempeh,[67] miso and doenjang
  • Kefir[citation needed]
  • Buttermil or Karnemelk
  • Kimchi [65], [68]
  • Kombucha[citation needed]
  • Pao cai[citation needed]
  • Sauerkraut[69]
  • Soy sauce[70]
  • Zha cai[citation needed]

Multi-probiotic


Research is emerging on the potential health benefits of multiple probiotic strains as a health supplement as opposed to a single strain.[71][72] 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:

Company Probiotic Strains Product
Nutri-Health Bifidobacterium bifidum, Bifidobacterium breve,

Bifidobacterium infantis, Bifidobacterium lactis,
Bifidobacterium longum, Lactobacillus acidophilus,
Lactobacillus brevis, Lactobacillus bulgaricus,
Lactobacillus casei, Lactobacillus gasseri,
Lactobacillus paracasei, Lactobacillus plantarum,
Lactobacillus rhamnosus, Lactobacillus salivarius,
Lactococcus lactis, Streptococcus thermophilus

 Flora Source Multi-Probiotic Formula
Enzymatic Therapy Lactobacillus acidophilus, Bifidobacterium longum Acidophilus Pearls
Kyolic Lactobacillus acidophilus, Bifidobacterium bifidum,

Bifidobacterium longum

 Kyo-Dophilus
Renew Life Bifidobacterium bifidum, Lactobacillus acidophilus,

Lactobacillus rhamnosus, Bifidobacterium breve,
Bifidobacterium longum, Lactobacillus casei,
Lactobacillus plantarum, Lactococcus lactis,
Lactobacillus bulgaricus, Lactobacillus salivarius

 Flora Smart

Research

Research about probiotics shows both benefits and harm.

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.[73]

A 2007 study at University College Cork in Ireland showed that a diet including milk fermented with Lactobacillus bacteria prevented Salmonella infection in pigs.[74]

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.[31]

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.[32]

Criticisms

Some experts are skeptical on the efficacy of many strains and believe not all subjects will benefit from the use of probiotics.[75] Another criticism[by whom?] is the cost and value of probiotics products.[75]

See also

  • Prebiotic (nutrition)

References

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