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The role of prebiotics in gastroenteric health

Glenn R Gibson
Professor of Food Microbiology School of Food Biosciences University of Reading

It can be difficult for many people to perceive microorganisms, especially bacteria, as anything other than harmful. While many microbes do have the capacity to cause disease, the vast majority of bacteria are harmless. For example, many advances in the biotechnology area have exploited the enzyme activities of bacteria to produce pharmaceuticals and other drugs such as antibiotics.
There is much variability in bacterial numbers and populations between the stomach, small intestine and colon. In comparison with other regions of the gastrointestinal tract, the human colon is an extremely densely populated microbial ecosystem. The large gut flora is now accepted as playing a major role in both human pathogenesis and health, with the colon being the body's most metabolically active organ - its resident microflora represents around 95% of all cells in the body. Through diet, its composition can be influenced such that microorganisms that are benign or even health-promoting can be stimulated. Certainly, a reduction in disease risk can occur as a result of fortifying selected microbial components.

Microflora modulation through diet
The large gut microflora is acquired at birth. Initially, strains such as Escherichia coli dominate. Thereafter, differences exist in the species composition that develops, and this is largely governed by a person's diet. The faecal flora of breastfed infants is dominated by populations of bifidobacteria, known as the "friendly" flora (eg, Bifidobacterium infantis and B longum, both of which are recognised probiotics), with only about 1% enterobacteria (eg, E coli). It is thought that certain bifidogenic factors are present in human breast milk. In contrast, formula-fed infants have a more complex microbiota with bifidobacteria, bacteroides, clostridia and streptococci all being prevalent. Bifidobacteria are powerful inhibitors of pathogens, which likely explains why "breast is best." After weaning, a complex pattern that resembles the adult flora becomes established.
It is clear that diet plays an important role in the maintenance and improvement of human health. The bacteria in the gut are dependent on food for growth and can be modified by a change in diet. To generalise, it is possible to categorise the gut microbiota components on the basis of whether they exert potentially pathogenic or health- promoting aspects. Lactic acid-producing genera such as the bifidobacteria or lactobacilli have a longstanding "health image". As such, attempts to stimulate microorganisms that carry out the latter could give obvious ­benefits over a more pathogenic flora.

Probiotics are defined as live microbial feed supplements that beneficially affect the host animal by improving its intestinal microbial balance. To be effective, probiotics must be capable of being prepared in a viable manner and on large scale (eg, for industrial purposes).
During use and under storage, the probiotic should remain viable, that is to say alive, and stable to survive in the intestinal ecosystem, while the host should gain beneficially from harbouring the probiotic. For probiotics to exert any beneficial properties they must have robust survival properties in the gut, which is their first point of contact. Moreover, they should not produce toxins, disrupt colonocyte function or have the ability to transfer antibiotic resistance to the normal gut microflora. Probiotics are being used in foodstuffs such as fermented milk products containing viable cultures perceived as beneficial (eg, lactobacilli, ­bifidobacteria).

An alternative or additional approach is the prebiotic concept. A prebiotic is a nondigestible 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 health of the host. The prebiotic approach advocates the administration of nonviable entities (nonliving foods). While any food ingredient that enters the large intestine is potentially a prebiotic, it is selectivity of the fermentation in the mixed bacterial environment that is critical and required.
At present, most prebiotics are selected on the basis of their ability to promote the growth of lactic acid- producing microorganisms. Dietary carbohydrates, such as fibres, are candidate prebiotics, but most promise has been realised with oligosaccharides. Hence, the approach is to use food ingredients to target beneficial components of the flora already in the gut. In turn, these are expected to repress pathogens through competition and the production of inhibitory substances. Prebiotics work therefore by selectively targeting the indigenous bacteria that are seen as advantageous.
As prebiotics exploit nonviable food ingredients, their applicability in diets is wide-ranging: they can be used as food supplements, incorporated into enteral feeds and added to products such as biscuits, cereals, spreads, drinks, dairy products, infant formulae, weaning foods and baked products. The incorporation of prebiotics into foods is a fast-moving area, and many novel formulations are being launched or are under development.
The most popular prebiotic ingredients in Europe are the fructo-oligosaccharides (eg, inulin). These have been proven in several human studies to increase bifidobacteria after a short feeding period. Inulin occurs naturally in several ingredients, such as onion, banana, garlic, artichoke, chicory root, asparagus, leek. The typical daily intake is 2-3g/d; however, upwards of 5g/d additional prebiotic is required for a bifidogenic effect. Others include lactulose (a synthetic compound often used as a laxative but given at sublaxative doses) and galacto-oligosaccharides.

Health benefits
The recent interest in prebiotics is easily explained by the potential health aspects that they confer:

Improved tolerance to lactose
It is thought that the target organisms for prebiotic use (probiotics already in the gut) may help because by increasing their number more lactose will be digested.

Protection from acute infections
A gut flora high in bifidobacteria and/or lactobacilli is inhibitory towards bacterial and viral pathogens. This may occur through the excretion of antimicrobial substances (eg, acids, antibiotics), competition for colonisation sites and nutrients. This also has relevance for more chronic diseases caused by pathogens (eg, ulcerative colitis, which is currently being trialled at the University of Reading).

Bowel cancer
Prebiotics are thought to inhibit the organisms that can produce carcinogens and generate beneficial metabolites (organic acids) that are efficient indicators of good digestion.

Coronary heart disease
It has been suggested that some gut bacteria can degrade cholesterol in the gut as well as produce metabolites that can block its production in the liver.

Vitamin production
Bifidobacteria can help to encourage the formation of  various vitamins, largely of the B group, which can help with the formation of blood cells and nerves, as well as improve food digestion.

Irritable bowel syndrome (IBS)
Prebiotics may help the gastrointestinal symptoms of IBS, and a study is underway at the University of Reading to determine the mechanism for this. The yeast Candida albicans, which seems prevalent in the disorder, is being targeted. This also has relevance for recurrent vaginal thrush caused by the same yeast.

Improved digestion and gut function
An active gut flora helps to adequately digest the 60-80g of food that enters the adult colon each day. The end- products of carbohydrate metabolism (eg, prebiotics) are entirely benign and may help to reduce protein fermentation, which can form toxins such as ammonia, and which may be carcinogenic.

Food allergy
It has been suggested that, by increasing levels of beneficial bacteria, the immune responses may be dampened, causing a reduction in the risk of symptoms associated with autoimmunity, such as eczema.

Immune regulation
A stimulation of the nonspecific immune response through nonpathogenic means may help improve resistance to infection.

Mineral bioavailability
A reduced pH in the bowel due to prebiotic fermentation is thought to improve the takeup of calcium and magnesium, which is important for bone and mineral density.

The microflora of the gastrointestinal tract is key for nutrition and health of the host. Microflora modulation can occur through diets that contain prebiotics. The use of diet to induce microbial change offers a very straightforward approach towards improved health that is consumer- friendly and effective.
There continues to be an exponential rise in the cost of pharmaceutical applications for human use. Moreover, the indiscriminate use of antibiotics has led to a reduction in their potency and efficiency. As such, attention has turned towards food materials that may offer improved health bonuses. Public and industrial perception of the importance of gut microbiology in human health and nutrition has led to a major increase in prebiotic-based products.
For the market value to be realised, however, it is imperative that such developments are based upon sound scientific principles that provide irrefutable information on efficacy. At the very least, the approach is harmless.

Case study
Prebiotic biscuits 31 students at the University of Reading were fed biscuits containing 8/g day prebiotic (fructo-­oligosaccharides) for 21 days. They were also given a placebo, which was identical apart from the ­omission of prebiotic. The trial was "crossover" in nature in that all volunteers took both biscuits. Neither the volunteers nor researchers knew which product was being ingested at which time, as the samples were prepared externally and blind-coded. During the trial, major gut bacteria were counted using a ­fluorescent probing procedure that targets particular genetic regions in the microbes. The only statistically significant change was a very large increase in bifidobacteria when the prebiotic was included. In fact, the gut flora profile approached that of breastfed infants. This did not occur with the placebo. The trial proved that prebiotics could be added to the diet and cause major shifts in the gut flora - towards beneficial microorganisms.