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 also by lowering the pH may create fewer opportunities for spoilage organisms to grow, hence creating possible health benefits on preventing gastrointestinal infections.[2]. Strains of the genera Lactobacillus and Bifidobacterium, are the most widely used probiotic bacteria.[3]
Probiotic bacterial cultures are intended to assist the body's naturally occurring gut flora, an ecology of microbes, to re-establish 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 to combat allergies, excessive alcohol intake, stress, exposure to toxic substances, and other diseases.[2][4] In these cases, 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 demonstratedcitation needed to support a healthy gut flora and may be another means of achieving the desirable health benefits promised by 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 laureateEli 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.[5] 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 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.[6]
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.[7] 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.[8] 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,[9] 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.[10] 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”.[11] Fuller’s definition emphasizes the requirement of viability for probiotics and introduces the aspect of a beneficial effect on the host.
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 faeces disappear within days when supplementation ceases.[13] While the oral use of probiotics is considered safe and even recommended by World Health Organization under specific guidelines [1], in some specific situations (such as critically ill patients) they could be potentially harmful. In one therapeutic clinical trial, a probiotic cocktail have been shown to increase the death rates of patients with acute pancreatitis [14], but was given through tube feeding directly in the intestine instead of the usual oral way. Some other therapeutic use of probiotics have been shown to be beneficial for other types of patients [2], [3].
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).[15]
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.[4] 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.[16] Animal studies have demonstrated that some LAB can protect against colon cancer in rodents, though human data is limited and conflicting.[17] Most human trials have found that the strains tested may exert anti-carcinogenic effects by decreasing the activity of an enzyme called β-glucuronidase[17] (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.[4]
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.[4]
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.[4]
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.[18][19]Clinical trials have demonstrated that probiotics may decrease the incidence of respiratory tract infections[20] and dental caries in children.[21] 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.[18][19]
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.[22]
Antibiotic-associated diarrhea
A meta-analysis suggested probiotics may reduce antibiotic-associated diarrhea.[23] A subsequent randomized controlled trial also found benefit in elderly patients.[24]
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.[27]
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.[28]
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.[29] Another probiotic bacterium, Lactobacillus plantarum 299V, was also found to be effective in reducing IBS symptoms.[30] Additionally, a probiotic formulation, VSL3, was found to be effective in treating ulcerative colitis[31] Bifidobacterium animalis DN-173 010 may help.[32]
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.citation needed
As probiotics are mainly active in the small intestine and prebiotics are only effective in the large intestine,[33] 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.citation needed
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.
Diarrhea and allergy reduction, immune stimulation, reduction of duration of winter infections, H. pylori eradication, antibiotic associated diarrhea & C. difficile infections (see Actimel)
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 diarrhoea and C difficile-associated diarrhoea.[24]
In a double-blind, placebo-controlled therapeutic study on the effects of a probiotic coktail on pancreatitis at University Medical Center Utrecht (UMC), 24 out of 296 patients died between 2004 and 2007, with more deaths among those receiving the probiotic coktail directly in the intestine. According to the spokesman of UMC, it is likely that some of these deaths would not have occurred without the probiotics [49], although other therapeutic trials conducted on probiotics were more positively conlusive [4].
References
^ 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.
^ abcde Sanders ME. Considerations for use of probiotic bacteria to modulate human health. J Nutr. 2000;130:384S-390S. Entrez PubMed10721912
^ Metchnikoff, E. 1907. Essais optimistes. Paris. The prolongation of life. Optimistic studies. Translated and edited by P. Chalmers Mitchell. London: Heinemann, 1907.
^ Vaughan RB. 1965. The romantic rationalist: A study of Elie Metchnikoff. Med Hist. 9:201-15.
^ Tissier, H. 1900. Recherchers sur la flora intestinale normale et pathologique du nourisson. Thesis, University of Paris, Paris, France.
^ Nissle, A. 1918. Die antagonistische Behandlung chronischer Darmstörungen mit Colibakterien. Med Klin 1918, 2:29-30.
^ 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.
^ Rettger, L.F., W.N. Levy, L. Weinstein, and J.E. Weiss. 1935. Lactobacillus acidophilus and its therapeutic application. Yale University Press, New Haven.
^ Fuller, R. 1989. Probiotics in man and animals. J. Appl. Bacteroil. 66:365-378.
^ Tannock, G.W. 2003. Probiotics: Time for a dose of realism. Curr. Intest. Microbiol. 4:33-42.
^ Beselink, MGM. "Probiotic prophylaxis in predicted severe acute pancreatitis: a randomized, double blind, placebo-controlled trial Lancet 14 Feb 2008".
^ Gilliland SE, Walker DK (Apr 1990). "Factors to consider when selecting a culture of Lactobacillus acidophilus as a dietary adjunct to produce a hypocholesterolemic effect in humans". J Dairy Sci73(4): 905–11. PMID 2111831.
^ 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 PubMed11157356
^ ab Brady LJ, Gallaher DD, Busta FF. The role of probiotic cultures in the prevention of colon cancer. J Nutr. 2000;130:410S-414S. Entrez PubMed10721916
^ ab Ouwehand AC, Salminen S, Isolauri E. Probiotics: an overview of beneficial effects. Antonie Van Leeuwenhoek. 2002;82:279-89. Entrez PubMed12369194
^ 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 PubMed11387176
^ 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 PubMed11799281
^ 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 PubMed14522098
^ 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 PubMed12182746
^ ab 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". BMJ335 (7610): 80. doi:10.1136/bmj.39231.599815.55. PMID 17604300.
^ 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 PubMed12548058
^ 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 PubMed12788576
^ 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 PubMed16095846
^ 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 Hepatol13 (10): 1143–7. doi:10.1097/00042737-200110000-00004.
^ 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.
^ 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.