Prebiotics and their effect in the diet

Recent years have seen a major increase in knowledge of the gut microflora composition and activities. It is thought that at least 500 different microbial species exist in the colon, the most heavily populated region of the gastrointestinal tract. Around 10-20 genera are likely predominate in numbers, and these include Bacteroides, Lactobacillus, Clostridium, Fusobacterium, Bifidobacterium, Eubacterium, Peptococcus, Peptostreptococcus, Escherichia, Veillonella¹.

While some indigenous bacteria can be pathogenic (eg proteolytic clostridia and bacteroides), it is also the case that some species may be advantageous for the host. For example, genera such as bifidobacteria and lactobacilli exert powerful anti-pathogenic capabilities and are mainly responsible for “colonisation resistance” in the gut.

Moreover, the same groups have been credited with other beneficial effects, such as stimulation of the immune response and generation of “protective” metabolites¹. While many of the health positive aspects have yet to be definitively proven in humans, it would appear that reducing potentially harmful bacteria while increasing the more beneficial community is of much value.

Probiotics

Probiotics are live microbial additions to appropriate food vehicles, usually fermented milks or freeze-dried products². A recent formal definition of probiotics was “a live microbial feed supplement that is beneficial to health”³.

Over the years many species of micro-organisms have been used. They consist of lactic acid bacterium (eg lactobacilli or bifidobacteria) but also Bacillus spp. and some yeasts⁴. The results of more than 50 human studies have generated a “positive” result from probiotic intake. These findings include improvements in the symptoms of irritable bowel syndrome and protection from traveller?s diarrhoea, as well as conditions systemic to the gut.

To be effective, probiotics should persist well in the gastrointestinal tract, which is an exceedingly competitive ecosystem. This has led to the development of prebiotics – a newer approach for microflora modulation.

Prebiotics

A prebiotic is defined as “a non digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria in the colon that can improve the host health”⁵. This approach targets indigenous beneficial bacteria to the gut and uses non-viable food ingredients to promote them selectively. Simply put, prebiotics can be seen as food for the beneficial bacteria in the colon. They are finding increasing use in functional foods, since there are few stability issues and they are resistant to heat. Prebiotic foods, either on the market or under development are given at annexe A below.

Human milk can be considered as the original prebiotic, in that it has a very powerful stimulatory effect on bifidobacteria. This in turn operates several mechanisms that can inhibit common pathogens (infectious agents of the gut), and as a result the flora of a breast fed infant are about 90 per cent bifidobacteria and these children experience far fewer gastrointestinal problems than those who are bottle fed. During weaning the bifidobacterial flora begin to decrease and throughout adult life their levels are 16-20 per cent of the total. In order to increase this, prebiotics may be taken. It takes about 5-8g of prebiotic per day to increase gut bifidobacteria.

Dietary carbohydrates, such as fibres are candidate prebiotics, but oligosaccharides (short-chain sugar molecules) have proven the most effective, through their ability to confer selectivity on the target bacterial species. In particular the ingestion of fructooligosaccharides (containing the carbohydrate fructose), like inulin, has been shown to stimulate bifidobacteria in the lower gut.

Criteria for classifying a food ingredient as a prebiotic include:

That it is resistant to gastric acidity, hydrolysis by mammalian enzymes and gastrointestinal absorption;

that it is fermented by intestinal microflora;

that it selectively stimulates the growth and/or activity of intestinal bacteria (such as bifidobacteria, lactobacilli) associated with health and well-being .

The prebiotic activity of fructose-containing oligosaccharides (FOS) has been confirmed in both laboratory and human trials^6-10. Bifidobacteria are able to break down and use fructo-oligosaccharides due to their possession of the necessary enzyme (competitive b-?fructofuranosidase¹¹.

Galacto-oligosaccharides (GOS), which contain the carbohydrate galactose, are another class of prebiotics that has been well researched. They have found application in infant formula foods as they are naturally present (albeit in very low quantities) in human milk.

Health related aspects

The ability of good prebiotics to stimulate bacteria like the bifidobacteria, seems to have been proven in several trials in various laboratories. The health benefits that may accrue from a gut microbiota high in bifidobacteria/lactobacilli is of major interest to both consumers and healthcare professionals. Several examples exist which have sound mechanistic based explanations of effect.

Intestinal Infections

This is probably the most reliable basis for the use of prebiotics and probiotics. A gut flora predominated by (harmless) lactic acid bacteria (LAB) can help resist the effects of acute pathogens that may be transmitted in food or water. This also has relevance for antibiotic associated diarrhoeas caused by individual microbial pathogens.

Our recent studies¹² have shown that the diarrhoea inducing capacities of enteropathogenic E. coli could be repressed through prebiotic use in primates. Monkeys and humans are 99 per cent genetically comparable and have similar gut flora composition, and so this is a very good model system for determining effects.

Lactose Malabsorption

Lactose malabsorption affects over half of the world?s population, and is as prevalent as excessive flatulence and/or diarrhoea. Probiotic bacteria contain the enzyme b-galactosidase which helps to digest lactose ¹³. In theory therefore, prebiotic based fortification of indigenous gut probiotics should help in this regard. This has not yet been proven however.

Reduced Risk of Chronic Gut Disorders

It has been suggested that certain microbial agents may be involved in chronic conditions. Therefore prebiotics may have value in reducing the risk of occurrence of these disorders, as follows:

There is very strong evidence for micro-organisms as a causative or maintenance factor for ulcerative colitis, a severe form of inflammatory bowel disease (IBD). Sulphate-reducing bacteria are ubiquitous in the colitic gut and produce toxic sulphides which have hugely destructive effects on colon cell function and may lead towards inflammatory lesions;

Crohn?s disease is a form of IBD that can affect any area of the alimentary tract. It has been suggested that certain mycobacteria may be involved, although the evidence is speculative;

Irritable bowel syndrome (IBS) is an extremely prevalent disorder which can present as diarrhoea and/or constipation. The yeast Candida albicans may be involved. At the University of Reading we have developed a pro/prebiotic based intervention designed to inhibit C. albicans;

Components of the gut flora have the capacity to produce carcinogens and tumour promoters from dietary components. Use of prebiotics to subvert the microflora involved may be useful. Moreover, their fermentation may lead towards protective metabolites like butyric acid. Butyrate is the preferred fuel for healthy colon cells, but also stimulates cell death in cancerous cells.

Whole System Effects

While the evidence is still fairly speculative, it is likely that end products formed by the microflora have non-localised effects. Acetate is transported to muscle (and other tissues) where it can be further metabolised to generate ATP, the energy currency of cells. Another bacterial end product, propionate, is thought to interfere with cholesterol synthesis by the liver.

On the contrary, the products of bacteria that metabolise protein are harmful, and have been associated with several conditions such as migraine, autistic spectrum disorders and colorectal cancer. The careful use of prebiotics to induce increased carbohydrate metabolism over proteolysis therefore has value.

Digestive Aid

It is thought that LAB help the digestion of carbohydrate based food materials. Prebiotics may therefore be directly related to their survival and ability to colonise effectively. A synbiotic is a probiotic and prebiotic mixture⁵.

Conclusion

Prebiotics are a “user friendly” approach towards gut flora modulation. Whilst certain food ingredients are touted as being prebiotics without definitive data to support this, there are some oligosaccharides that have well proven efficacy. As a relatively new concept, the health promoting properties of prebiotics are highly promising ? and with no safety issue over their use, they can be recommended without concern. The beneficial properties are being identified and the research is moving quickly. This has largely occurred through the consolidated and collaborative activities of organisations such as International Scientific Association for Probiotics and Prebiotics (www.isapp.net) and the EU funded research cluster (Pro-EU-Health) Both organisations have very effectively harnessed scientists from different disciplines to effectively address the research issues and mechanisms involved in pro/prebiotic interventions. This has allowed sufficient “critical mass” to be put behind identifying the realistic basis for their use.

References

1. Gibson, G.R. and Roberfroid, M.B. (eds.) 1999. Colonic Microbiota, Nutrition and Health. Kluwer Academic Publishers, Dodrecht.

2. Fuller, R. 1989. Probiotics in man and animals. Journal of Applied Bacteriology 66, 365-378.

3. Salminen, S., Bouley, C., Boutron-Ruault, M-C., Cummings, J.H., Franck, A., Gibson, G.R., Isolauri, E., Moreau, M.C., Roberfroid, M.B. and Rowland, I.R. 1998. Functional food science and gastrointestinal physiology and function. British Journal of Nutrition 80, S147-S171.

4. Collins, M.D. and Gibson, G.R. 1999. Probiotics, prebiotics and synbiotics: Dietary approaches for the modulation of microbial ecology. American Journal of Clinical Nutrition 69, 1052-1057.

5. Gibson, G.R. and Roberfroid, M.B. 1995. Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. Journal of Nutrition 125, 1401-1412.

6. McCartney, A.L. and Gibson, G.R. 1998. The application of prebiotics in human health and nutrition, In: Proceeding Lactic 97. Which Strains? For Which Products? Adria Normandie, pp. 59-73.

7. Wang, X. and Gibson, G.R. 1993. Effects of the in vitro fermentation of oligofructose and inulin by bacteria growing in the human large intestine. Journal of Applied Bacteriology 75, 373-380.

8. Williams,C., Witherly, S.A. and Buddington, R.K. 1994. Influence of dietary neosugar on selected bacterial groups of the human faecal microbiota. Microbial Ecology in Health and Disease 7, 91-97.

9. Kleessen, B., Sykura, B., Zunft, H-J. and Blaut, M. 1997. Effects of inulin and lactose on fecal microflora, microbial activity and bowel habit in elderly constipated persons. American Journal of Clinical Nutrition 65 1397-1402.

10. Gibson, G.R., Beatty, E.R., Wang, X. and Cummings, J.H. 1995. Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin. Gastroenterology 108, 975-982.

11. Imamura, L., Hisamitsu, K. and Kobashi, K. 1994. Purification and characterization of fructofuranosidase from Bifidobacterium infantis. Biological and Pharmacological Bulletin 17, 596-602.

12. Brück, W.B., Kelleher, S., Gibson, G.R., Nielsen, K.E., Chatterton, D.E.W. and Lönnerdal, B. 2003. rRNA probes used to quantify the effects of glycomacropeptide and a-lactalbumin supplementation on the predominant groups of intestinal microflora of infant rhesus monkeys challenged with enteropathogenic Escherichia coli. Journal of Pediatric Gastroenterology and Nutrition 37, 273-280.

13. Fuller R (ed.) 1997. Probiotics 2: Application and Practical Aspects. Chapman and Hall, Andover, UK.

Annexe A

Examples of foodstuffs that can be fortified with prebiotics

Dairy products Beverages and health drinks, Spreads Infant formulae and weaning foods Cereals Bakery products Confectionery chocolates, chewing gum Savoury products and soups Sauces and dressings Meat products Dried instant foods Canned foods Food supplements Agricultural feeds Pet foods

Professor Glenn Gibson is head of the Food Microbial Sciences Unit, School of Food Biosciences, University of Reading.