ProbioticsProbiotics are living bacteria or other microorganisms which may be beneficial to the health of humans or animals when consumed. Beneficial bacteria include Lactobacillus and Bifidobacterium spp. and other lactic acid bacteria. Much has been written in both the medical literature and lay press about their potential benefits, some of it well validated by randomized controlled trials but other claims remain unsubstantiated. There is, however, a growing body of evidence for the role of probiotics in gastrointestinal infections, irritable bowel syndrome and inflammatory bowel disease. Provided here is information on the science of probiotics, recent scientific research on probiotics and current research topics of interest to scientists and clinicians.
- What are Probiotics?
- The Intestinal Microflora
- Probiotics for Farm Animals
- Methods for Analysis of the Intestinal Microflora
- The Hygiene Hypothesis: The Role of Microbes in the Prevention of Atopy and Atopic Disease
- Probiotics and Prebiotics: Where are We Going?
- Fluorescence In Situ Hybridization as a Tool in Intestinal Bacteriology
- From Composition to Functionality of the Intestinal Microbial Communities
- Genus- and Species-Specific PCR Primers for the Detection and Identification of Bifidobacteria
- Prebiotic Oligosaccharides: Evaluation Of Biological Activities and Potential Future Developments
- Prebiotics and Calcium Bioavailability
- The Possible Role of Probiotic Therapy in Inflammatory Bowel Disease
- Gut Microflora and Atopic Disease
- Genomic Perspectives on Probiotics and the Gastrointestinal Microflora
- Intestinal Microflora and Homeostasis of the Mucosal Immune Response: Implications for Probiotic Bacteria?
- Probiotics and Prebiotics: Scientific Aspects (2005). By Gerald Tannock. For information about this major volume please visit Probiotics Book.
- Probiotics and Prebiotics: Where are We Going? (2002). Edited by Gerald Tannock. Probiotics and Prebiotics
What are Probiotics?
A "probiotic", by the generally accepted definition, is a "live microbial feed supplement which beneficially affects the host animal by improving its intestinal microbial balance". Although referring to the supplementation of animal feeds for farm animals, the definition is easily applied to the human situation. The major consumption of probiotics by humans is in the form of dairy-based foods containing intestinal species of lactobacilli and bifidobacteria. It is implicit in the definition that consumption of the probiotic affects the composition of the intestinal microflora. This effect of the probiotic on the intestinal ecosystem, it is proposed, impacts in some beneficial way on the consumer. A number of potential benefits arising from changes to the intestinal milieu through the agency of probiotics have been proposed, including:
· increased resistance to infectious diseases, particularly of the intestine· decreased duration of diarrhoea· reduction in blood pressure· reduction in serum cholesterol concentration· reduction in allergy· stimulation of phagocytosis by peripheral blood leucocytes· modulation of cytokine gene expression· adjuvant effect· regression of tumours· reduction in carcinogen or co-carcinogen production
Perhaps surprisingly, despite this impressive list of therapeutic and prophylactic attributes, probiotics are not commonly part of the medical practitioner's armamentarium of prescription drugs. Instead, probiotics are available from retail outlets, usually supermarkets, grocery and health food stores. The probiotics are available to the consumer as powders or tablets, but most commonly as milk-based products. The growth in the production of probiotics by the dairy industry means that it is now increasingly difficult to purchase yogurts that do not contain "probiotic" bacteria such as Lactobacillus acidophilus. They sell well, but it is very doubtful that probiotic yogurts are purchased entirely for health reasons. Consumers may be purchasing probiotics with the vague idea that it is "good for them": that consumption of the product will contribute to their well-being. Since even some scientists treat the "probiotics" concept with scepticism, how can the average consumer hope to comprehend the significance of "acidophilus" or "bifidus" in any but the simplest of contexts? Many others purchase probiotic dairy products because they prefer the organoleptic and rheologic characteristics of these products in comparison to "regular" yogurts. Whatever the reason, there are consumers who hold a firm belief that their health is improved by regular consumption of a probiotic. It becomes almost an article of faith. Others are suspicious of the probiotic industry, and question the validity of the claims made in relation to health benefits. And, it must be admitted, they have some basis for these doubts: the marketing strategy for probiotics relates to health benefits and therefore to medical science. Yet even the most ardent advocates of the probiotic concept must admit that the "science" associated with probiotics over many decades has been remarkably weak. Why else has the medical profession, and much of the scientific community, remained aloof from the results of probiotic research?
Despite doubts in scientific circles as to its validity, the probiotics industry is flourishing, and interest in establishing scientific credibility has attained importance for many companies and scientists. European Union programmes are to the fore in this work. It is an unusual and difficult situation for scientists, however, because probiotic products have been in existence for decades, yet they must now search for experimental evidence to support long-held beliefs associated with products already in the retail market. The probiotics industry is burdened with myth (anecdotal studies) and a reliance on in vitro experimentation. Much effort has been devoted to screening bacterial isolates for properties deemed appropriate for a "probiotic" strain, mostly characteristics that might enable the microbes to at least survive passage through the digestive tract. There must be millions of such strains to choose from, because the intestinal milieu of humans is already the home to bacteria with these properties. Probably the biggest obstacle to allaying scepticism is that the probiotic concept is based on a very poor understanding of the intestinal microflora. The concept concentrates essentially on two groups of bacteria, lactobacilli and bifidobacteria, while practically ignoring the vast array of other species that inhabit the intestinal tract of humans. It is the impact of probiotics on the composition of the intestinal microflora, nevertheless, that forms the basis for the probiotic concept. What can currently be said about the impact of probiotic bacteria on microbial balance at the moment? "They go in at one end of the digestive tract and come out the other, and hopefully something good happens along the way" is probably not too harsh a statement. Can anyone define the "microbial balance" to which one aspires in the definition of a probiotic?
While there is a current trend to conduct "clinical trials" to prove the efficacy of exisiting probiotics, it may be better to return to a consideration of fundamental principles of microbial ecology, human physiology and immunology before embarking on these very costly exercises. What are the "beneficial effects" that one wants to produce by using probiotics? Do we know how to recognise the beneficial effects mentioned in the definition of a probiotic? Better, perhaps, to allocate funds to the utilisation of molecular biological tools in the analysis of the complicated systems which must be investigated. With these tools, a better understanding of the interactions between members of the intestinal microflora and between the microflora and the human host could be established. The intestinal bacteria could then be used as mediators to modulate phenomena that are of significance to human health. The development of modern pharmaceutical drugs is based on fundmental knowledge of processes occurring within the human body. Mechanisms of drug action are known, and explanations of efficacy can be publicised. To attain scientific validity, probiotics must be derived by the application of logic.
The Intestinal Microflora
The study of the intestinal microflora is a crucial aspect of probiotic research and development. Comparative studies with germfree and conventional animals, strictly anaerobic culture methods and microscopy have provided the knowledge on which current concepts of the intestinal microflora are based. The application of molecular methodologies will enhance knowledge of the complex microbial ecology of the intestinal tract and enable a modern concept of the intestinal microflora and microflora-host relationships to be developed.
A range of non-digestible dietary supplements have now been identified that modify the balance of the intestinal microflora, stimulating the growth and/or activity of beneficial organisms and suppressing potentially deleterious bacteria. Termed "prebiotics" these supplements include lactulose, lactitol, a variety of oligosaccharides, and inulin. In particular, prebiotics promote the proliferation of bifidobacteria in the colon. The science of prebiotics is still in its infancy and as yet there is a dearth of reported clinical trials demonstrating clear efficacy in the prophylaxis or treatment of human disease. However, research to date indicates that prebiotics have potential to positively influence human health.
Probiotics for Farm Animals
The development of probiotics for farm animals is based on the knowledge that the gut microflora is involved in resistance to disease. The stressful conditions experienced by the young animal causes changes in the composition and/or activity of the gut microflora. Probiotic supplementation seeks to repair these deficiencies and provide the type of microflora which exists in feral animals uninfluenced by modern farm rearing methods. The products available are of varying composition and efficacy but the concept is scientifically-based and intellectually sound. Under the right conditions the claims made for probiotic preparations can be realised.
Methods for Analysis of the Intestinal Microflora
The concept of probiotics has been around for nearly 100 years. Yet its impact on human nutrition is still an emerging concept. Lack of convincing scientific validation for the efficacy of any ingested probiotic bacterium on intestinal health, has been a major reason for the low impact of probiotics on human nutrition. Obtaining positive scientific validation requires the use of suitable probiotic strains and also the necessary tools to monitor the performance of these bacteria in the intestines of individuals. To date, selection of strains for probiotic purposes has not been based on a scientific directed approach, primarily because it is not yet fully known what specific traits a desirable probiotic strain should possess. Filling this knowledge void will depend largely on furthering our understanding of the human intestinal ecosystem and the functional role of specific bacteria for intestinal health. Traditional approaches for studying this ecosystem have provided a good foundation in this knowledge base. Complementation of the traditional approaches with the emergence of sophisticated molecular tools shows enormous promise for obtaining the necessary insight into the intestinal microflora.
The Hygiene Hypothesis: The Role of Microbes in the Prevention of Atopy and Atopic DiseaseMicrobiology Books.
Probiotics are microbes present in the human gut that have a beneficial effect on the human immune system, opposed to pathogens that can have harmful effects (Schrezenmeier, 2001). Several mechanisms of action have been proposed by in-vitro studies, but the precise mechanism remains to be elucidated (Isolauri et al., 2001). In the only primary prevention study performed so far, 1010 colony forming units (cfu) of Lactobacillus GG was administered daily for 2-4 weeks before expected delivery to pregnant women with a positive family history of atopy, and to their offspring during the first 6 months of life in a randomised, placebo-controlled design. At the age of 2 years, the frequency of eczema in the intervention group was half that of the placebo group. This suggests that LGG given prior to birth, and for a prolonged period early in life may decrease the incidence of eczema (Kalliomaki et al., 2001). At the age of four years, follow-up was performed in 107 of the children who participated in the study at the age of two (Kalliomaki et al., 2003). The incidence of eczema was significantly lower in the children who received LGG (14 out of 53) compared to the children who received the placebo (25 out of 54), implicating a relative risk of 0.57 with a 95% confidence interval of 0.33-0.97. No significant difference in the incidence of asthma and rhinitis was found between the two groups. The authors conclude that these results suggest that the preventive effect of LGG on AD extends beyond infancy. A shortcoming of this study is the low number of children examined at the last follow up, implicating that a selection bias cannot be excluded. Furthermore, no difference in serum IgE concentration and in the number of positive skin-prick tests was found between the intervention and the control-group. This suggests that treatment with LGG results in a reduction of the incidence of non-atopic eczema rather than atopic dermatitis (Niers et al., 2003). Other studies addressing this issue are definitely required before definite conclusions can be drawn on the preventive effect of LGG in high-risk infants with respect to the development of atopic disease. In a tertiary prevention study, LGG (2x1010 cfu twice daily) was administered for 1 month to 14 infants (2.5-15.7 months of age) with cow's milk allergy and AD in a randomised double-blind, placebo-controlled study design. All children were fed an extensively hydrolysed whey formula. In the intervention-group, a reduction in the SCORAD-score, in faecal TNF-a, and in a-1-antitrypsin was found compared with the placebo-group. This suggests that administration of LGG results in a decrease in intestinal and systemic inflammation and in a decrease in mucosal permeability (Majamaa et al., 1997). Comparable results were found with Bifidobacterium Bb-12 and LGG administration in even younger infants (mean age 4.6 months) with AD. Despite several shortcomings in both studies, the authors of these studies suggested that these probiotics may be used as treatment of infant AD (Isolauri, 2000). However, these results could not be confirmed in a recently performed study, in which a combination of 2 strains of Lactobacilli (rhamnosus and reuteri) was administered in 1-13 years old children with AD. The only significant difference between the probiotic- and the placebo-group was found in a subjective dermatitis severity parameter (the children or parents evaluated the eczema as "better, unchanged or worse" after either treatment). During administration of probiotics, the eczema was significant more frequently evaluated as better (Rosenfeldt et al., 2003). The reason for the discrepancy between the latter study and the former studies is not entirely clear, despite the different age-groups studied, the different probiotics administered, and the different dose of probiotics used. More studies are needed on this issue before definite conclusions can be drawn.
Probiotics and Prebiotics: Where are We Going?
Fluorescence In Situ Hybridization as a Tool in Intestinal Bacteriology
From Composition to Functionality of the Intestinal Microbial Communities
Genus- and Species-Specific PCR Primers for the Detection and Identification of Bifidobacteria
Prebiotic Oligosaccharides: Evaluation Of Biological Activities and Potential Future Developments
Prebiotics and Calcium Bioavailability
The Possible Role of Probiotic Therapy in Inflammatory Bowel Disease
Gut Microflora and Atopic Disease
Genomic Perspectives on Probiotics and the Gastrointestinal Microflora
Intestinal Microflora and Homeostasis of the Mucosal Immune Response: Implications for Probiotic Bacteria?
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