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The term “probiotic” covers microbial food supplements whose primary aim is to improve the health and well being of the consumer. It comprises not only products specifically designed to produce health benefits, but also traditional yoghurts and bioyoghurts which contain special bacteria of intestinal origin. A more formal definition widely used is: “A live microbial food supplement which beneficially affects the host animal by improving its intestinal microbial balance”. (Fuller, 1989). This definition emphasises the need for the probiotic preparation to contain viable micro-organisms. The difficulty
of maintaining viability over long storage periods has led to confusing results in the past.

Fig. 1: Electron micrograph showing lactobacilli adhering to the
squamous epithelium of the pig stomach

The intestinal microflora

At birth the intestinal tract of the baby is sterile, but it rapidly acquires micro-organisms from its mother and the environment. In nature, the major source of micro-organisms would be the mother, but in the developed world the standards of hygiene practised in the hospital and the home restrict the transfer of microbes from mother to offspring. The increase in bottle feeding has also had a deleterious effect on the development of the microbial population in the intestines (the so-called gut microflora). In spite of attempts to simulate the composition of breast milk, formula milk-fed babies have significant differences in the composition of their gut microflora.

After weaning on to solid foods, the gut microflora changes and, by about one year, the composition resembles that of the adult. The composition of the adult gut microflora is fairly stable but can be affected by such factors as diet, medication, environmental stress (temperature and humidity) and emotional stress. It is these adverse changes in the gut flora that probiotics seek to reverse and/or prevent.

The flora which eventually develops is a very complex collection of hundreds of different types of bacteria which may be affecting each other and influencing the host. There is a delicate balance which exists in the normal healthy individual where the ‘good’ bacteria suppress the potentially ‘bad’ bacteria. This results in a symbiotic association between the flora and the host. This exchange has been evolved to work under natural conditions to the benefit of the host but modern lifestyles, especially in developed countries, have compromised the association and, in some circumstances, have left the host vulnerable.

How do we know that the gut microflora is doing its job of protecting the host against disease? The evidence comes from three sources:

1.    if animals are reared in the complete absence of microbes (germfree) they are more susceptible to diseases such as cholera, dysentery and salmonellosis.
2.    antibiotics given orally often induce diarrhoea. The antibiotic is killing off the protective microbes and allowing the dangerous pathogens to multiply.
3.    the diarrhoeal conditions induced by antibiotic feeding can be treated, by dosing with an enema prepared from a suspension of faeces from a healthy adult.

The evidence for the protective effect of the gut flora is, therefore, incontrovertible. The aim of probiotics supplements is to ensure that the microbes responsible for the protection are present in the intestine.

Development of probiotics

Evidence for fermented milks goes back to pre-Christian times. Sumerian cave drawings show what appears to be men transferring material from the soured milk to urns of fresh milk to maintain the fermentation. Although this fermented milk was not produced as a health food, the improvement in keeping quality of the milk would undoubtedly have had an effect on the health of the consumers.

It was not until the beginning of this century that Metchnikoff, working at the Pasteur Institute in Paris, put the practice on to a scientific footing. He was convinced that the microbial flora of the lower gut was having an adverse effect on the host – what he called ‘auto intoxication’. He had also observed that Bulgarian peasants lived to a ripe old age and also consumed large quantities of soured milk. Without any good evidence, he related the two. Subsequent events have tended to confirm this relationship. He attempted to repeat the effect by isolating pure cultures of organisms and using them in his experimental trials. One of the organisms he described is one of those which is now used in yoghurt. (Lactobacillus delbrueckii subsp. bulgaricus).

The other line of approach was the use of bacteria isolated from the intestine. When Metchnikoff died, the centre of research moved from Paris to the USA. At Yale, Rettger and his colleagues reasoned that if the organism was to grow and have its effect in the intestine, it seemed likely that organisms isolated from the gut would have more activity. They isolated and used a bacterium called Lactobacillus acidophilus which they found to be active in ameliorating the effects of constipation. A great deal of work has been done with this species over the years, but it soon became obvious that this was not the only lactobacillus in the gut and several other species are now commonly included in probiotic preparations.

Probiotics now contain not only lactobacilli but other lactic acid bacteria such as bifidobacteria, enterococci and streptococci. Other unrelated microbes used in probiotics are yeasts (Saccharomyces cerevisiae, Sac. boulardii), filamentous fungi (Aspergillus oryzae) and some spore forming bacilli.

Probiotics can be presented to the consumer in various forms. As well as the fermented milk now commonly available in supermarkets, there are probiotics available as tablets, powders and liquid suspensions. There are also products sold, mainly in Japan, in which probiotic micro-organisms are incorporated into confectionery and fruit drinks.

Probiotic Usage

In human consumption the two main benefits are improved nutrition and increased resistance to disease. The most convincing evidence is for improvement in resistance to infectious disease although claims have been made based on trials in experimental animals that probiotics can reduce the incidence of cancer and coronary heart disease. The experimental evidence in animals is very encouraging but the confirmation of the effect in humans remains to be produced.

There are many anecdotal reports of positive effects and much of the experimental evidence is derived from trials which were poorly designed and inadequately analysed. But there are well controlled studies which give significant positive effects and prove that given in the right way under the right conditions, probiotics can achieve much of what is claimed for them. Some examples are given below.

The inability to digest lactose is a condition that afflicts over half the world’s population. Ingestion of milk results in stomach cramps and diarrhoea. Subjects suffering from this lactose maldigestion can, however, tolerate the same amount of lactose when given in the form of yoghurt. The reason is still obscure with some authorities claiming that the increased lactose activity is originating from the gut flora, whereas others detect it in the gut epithelium.

The antibiotic induced diarrhoea is usually caused by an organism called Clostridium difficile and can be a very persistent infection. Good results have been obtained by treatment with probiotics. In a double-blind placebo controlled study by McFarland and her colleagues in the United States, it was shown that treatment with Sac. boulardii gave a reduction in incidence of diarrhoea of 50% and this result was statistically significant. Similar results were obtained by Wunderlich and colleagues in Switzerland using strain SF68 of Enterococcus faecium.

Diarrhoea in children is often caused by rotavirus infection. This also can be controlled with probiotics. Isolauri and her colleagues in Finland studied the effect of treatment with L. rhamnosus GG in children aged 4-45 months. There was a significant reduction in the duration of the diarrhoea when the probiotic was given as a powder or as a fermented product. The results were even more significant when the data was related to those patients with confirmed rotavirus infections.

In another carefully controlled trial, children aged 5-24 months who were in hospital for non-gastrointestinal conditions were given Bifidobacterium sp and Strep. salivarius subsp. thermophilus as a probiotic treatment. After 17 months on the treatment there had been a significant reduction in the incidence of diarrhoea in the probiotic group when compared with the control group given no treatment.

Chemotherapy for leukaemia often results in intestinal upsets caused by Candida overgrowth. In a trial in Japan conducted by Tomoda leukemia patients were treated with a milk containing L. acidophilus and Bifidobacterium sp. There was a marked reduction in the count of Candida in the faeces.

Results such as these show that probiotics can have beneficial therapeutic effects in a wide variety of different intestinal disorders caused by a range of different aetiological agents. As well as these effects on established disease, probiotics are recommended as a routine food supplement to restore the gut flora back to its full protective complement and act by preventing diseases in the gastrointestinal tract.

How do they work?

Little is known about the way in which probiotics are able to inhibit other micro-organisms in the gut. But we can speculate about how they may be operating by reference to existing knowledge on microbial interaction in the gut. Probiotics may be having their effect by one or more of the following methods:

1.    Competition for nutrients. The gut is such a rich source of nutrients that this seems unlikely, but it should be remembered that it only requires the absence of one essential nutrient to prevent the growth of a micro-organism. There is some evidence that this type of mechanism is at least partly responsible for the inhibition of Cl. difficile by the gut microflora.
2.    Direct chemical inhibition. Lactic acid bacteria are known to produce a variety of different antibiotic-like substances. However, their activity in the gut has never been demonstrated and this seems an unlikely explanation.
3.    Competition for adhesion sites on the gut wall. Many gut pathogens, in order to colonise the gut, have to attach to the lining of the intestinal tract. This enables them to survive the flushing effect of peristalsis. If the probiotic organism attaches preferentially to the gut wall and prevents the pathogen adhering it will be unable to colonise and produce disease. There is good evidence that lactobacilli, commonly used in probiotic preparations, can adhere to the gut wall (see Fig. 1).
4.    Stimulation of immunity. A great deal of work has been done recently in laboratory animals which demonstrates that administration of lactic acid bacteria by mouth can stimulate the immune system. Perdigon and her colleagues in Argentina have shown that the increase in antibody level is related to the reduction in salmonella. Recent work by Nestlé in Switzerland has shown that similar immune responses can be induced in human subjects by administration of L. acidophilus LC1. The recognition that lactic acid bacteria can stimulate an immune response is a very important finding because it means that there is now a mechanisms for the probiotic to have an effect in sites outside the intestinal tract.

The composition of probiotic preparations varies greatly and it is likely that no one mechanism would explain the activity of all probiotics. However, there seems little doubt that one or more of the above suggested mechanisms will be responsible for the antimicrobial activity of many probiotic preparations.

Further reading

Fuller, R. 1989 Probiotics in man and animals. J. Appl. Bact. 66, 365-378.
Fuller, R. (ed) 1992 Probiotics. The Scientific Basis Chapman & Hall: London
Fuller, R. (ed) 1997 Probiotics 2. Applications and Practical Aspects Chapman & Hall: London
McFarland, L.V. & Elmer, G.W. 1995 Biotherapeutic agents: Past, present and future. Microecology and Therapy 23, 46-74.
Salminen, S. & von Wright, A. 1993 Lactic Acid Bacteria Marcel Dekker Inc: New York.