The role of the many and varied bacteria which inhabit the digestive system is coming to be seen as a major factor in human health – despite the relatively little we know about them. It is also giving rise to so-called 'probiotic foods' with their potentially beneficial effects on the immune system.
The image shows a mixture of two pure cultures of Lactobacillus intestinalis (the green elongated elements) and Bifidobacterium longum (pinkish 'grains') as seen through a microscope. In some cases, an increased presence of these microorganisms in the intestinal flora can have probiotic effects which help strengthen immunity against many pathologies of bacterial origin.
They are present in their billions, belonging to some 500 different species. They exist in a very intimate relationship with our bodies, yet we never see them. The bacteria which inhabit our digestive tract form a vast community of uninvited guests whose influence on our health is confirmed regularly by scientific studies.
In addition to regulating the efficiency of intestinal activity – the intake of nutrients and the elimination of waste, they also seem to influence the workings of our immune system. The bacterial fauna in our intestines can also cause serious problems by promoting the development of virulent or even deadly pathogens. Conversely, a bacterial population in which these aggressors are unable to grow is a sign of good health.
What lies beneath Despite its importance, we know very little about this intestinal fauna. To fill this gap, Proeuhealth – a cluster of European projects bringing together 64 research teams from 16 countries – was set up to investigate them.
Tiina Mattila-Sandholm of the Finnish Institute VTT Biotechnology, which coordinates Proeuhealth, describes the digestive tract as a 'black box'. 'Even today, in 2003, nobody can say exactly what the microbial ecosystem in our intestines really consists of,' she stresses.
What species are found there? How do they affect our health? What exactly are the 'good bacteria' – also known as probiotic bacteria – and how do they function? How can we develop foods which use them to optimal effect? These are just some of the questions into which researchers on the Proeuhealth project are looking. Launched two years ago, it plans to submit its findings by 2005.
Controlling the claim game
Lactobacillus seen in cross-section, magnified 66 000 times.
Probiotics are of just as much interest to health authorities as they are to food producers and consumers. We know that the ingestion of certain microbial strains (Lactobacillus and Bifidobacterium most notably) can have a particularly beneficial effect on health.
However, these benefits have only been demonstrated under very specific conditions. A number of tests have shown, for example, that certain strains of Lactobacillus can protect an infant against viral diarrhoea. Such results cannot be attributed to all probiotics of course – two strains of the same species can have almost the opposite effect – and even less so to the total bacterial population.
Despite this, a number of decidedly dubious extrapolations are made. Some food producers try to create an image of a 'healthy food' by making claims that too often go far beyond the scientific reality: 'stimulates the immune system' or 'restores balance to the intestinal flora'.
'I sincerely hope that our results will make it possible not just to improve the health of the population, but also to restore some order to this marketing jungle,' continues Mattila-Sandholm. 'But for that we need precise results, particularly on the mechanisms."
A division of Escherichia coli, a bacteria commonly found in the human intestines and other warm-blooded animals, magnified 200 000 times. Some varieties of E. coli produce toxins which can cause serious enterohaemorrhagic diseases transmitted by food.
Rigorous progress in this multifaceted investigation requires a thorough understanding of the exact nature of the intestinal bacteria and finding the means to differentiate between them. The Microbe Diagnostics project aims to do just that.
Headed by Michael Blaut, a young and enthusiastic researcher from the German Institute of Nutrition (DIFE – Potsdam), the research team is trying to draw on the latest results in molecular biology to make the most precise possible analysis of the composition of the intestinal ecosystem.
A number of techniques (flow cytometry, in situ fluorescence, RNA measurements) are used to detect significant sequences – or signatures – of the organisms present.
'We knew very little at the outset,' explains Michael Blaut. 'This is because science was, for a long time, only interested in organisms we knew how to grow, which is just a very small proportion of those we are now studying. Also, there was a tendency to concentrate on pathogens rather than the 'normal' intestinal flora – if such a word has any meaning as the variations between one individual and another, and even for the same person at different ages, are so great. Finally, the molecular tools have not been available for very long. We have, nevertheless, made major progress in recent years and we now have an inventory with which it is possible to work.'
The team from Microbe Diagnostics has already carried out 16 oligonucleotide probes making it possible to detect certain micro-organisms rapidly. As our knowledge develops, new probes can be developed more quickly, resulting in an increasingly wide range of tools. These can then be made available to other researchers, to find the link between a pathology and a given bacterial strain for example, to test the effects of diet on the presence of a particular bacteria, or to analyse the overall development of the intestinal flora.
Under the microscope These new developments should help shed light on mechanisms we barely understand. In fact, we do not even know how a microbe is able to act on the general condition of its host.
Deprohealth and Propath, two projects in the Proeuhealth cluster, have been charged with shedding light on of the principal mysteries of probiotics: the effect they have on the immune system.
Two kinds of antagonistic pathologies are currently under the microscope. The first is inflammatory bowel disease (IBD for short), which affects many Europeans and is essentially caused by an excessive immune reaction. The second are viral (rotavirus diarrhoeas) or bacterial infections, which are indicative of the opposite phenomenon: the inability of natural defences to overcome a pathogen.
Among the bacteria the researchers are paying particular attention to, the best known is Helicobacter pylori, which is responsible for ulcers, gastritis, and various kinds of salmonella (a common cause of food poisoning).
The teams are working with different strains of Lactobacillus and Bifido bacterium. They are trying to discover which of the molecules produced – especially by the bacterial wall – have health benefits, how they achieve this, and more precisely the type of immune reactions they encourage or prevent. Once the mechanisms are identified, the teams create ad hoc strains and, to quote Deprohealth coordinator Annick Mercenier of the Institut Pasteur in Lille, try to produce 'original therapeutic agents making it possible to obtain innovative anti-inflammatory treatment and oral vaccines against H. pylori and the rotaviruses.'
A third project, EU & Microfunction, is also looking into the question of mechanisms. It is particularly interested in the effect of diet on the bacteria in the human gut. This can result from the consumption of bacteria (probiotics) or particular foods – prebiotics – which stimulate the development of a particular probiotic. Once again, we do not know why or how a particular food favours the development of a given bacterial strain.
Healthy outcomes The improvement of human health is central to the aims of the Proeuhealth cluster. One associated project, Progid, is investigating two particularly debilitating intestinal diseases, ulcerous colitis and Crohn's disease. The latter is a serious autoimmune infection which, in some cases, can require the surgical removal of entire sections of the digestive tract.
To define the possible effects of probiotics on these pathologies, two large-scale double-blind tests – in which neither the evaluators nor the subjects know which items are controls – are being carried out in a number of countries over a period of approximately one year.
Crownalife is another project linked directly to health. The project’s co-ordinator, Joël Doré of France’s Institut National de la Recherche Agronomique (INRA), explains that: 'Old people represent a growing proportion of the European population… As this group is more sensitive to degenerative diseases and infections there is a growing need to develop preventive nutritional strategies.'
Each age group has its own specific demographic for its intestinal population. Understanding this evolution and its health implications is the first step towards effective nutritional advice and, ultimately, 'a new generation of functional foods'.
Cross-section of the colon showing the presence of amoeba. In this parasitic infection of the large intestine, frequent in tropical countries, the pathogenic agent crosses the wall of the large intestine and can sometimes reach the liver (hepatic amebiasis).
The already considerable global market in probiotics is destined to grow. It is perhaps unsurprising that industry (including SMEs) is participating in various EU-backed projects in the field.
Protech, for example, includes five companies among its 12 partner laboratories. The project aims to improve the technological aspects of producing probiotic foods. Generally of the lacteal variety, probiotics usually come in for considerable punishment, whether during industrial processing (heating, freezing, lyophilisation and conservation) or in the body itself (stomach acids, digestive enzymes and bile juices).
Even an excellent probiotic is only of value if it arrives alive in our intestines. 'We have a number of strategies for achieving this,' explains Dietrich Knorr of Berlin's Technological University. 'We can look for protective molecules and then combine them with microbes. We have achieved excellent results with certain pectins. We can also stimulate the natural defences of probiotics. When heated to 50°C, some microbes produce specific proteins which protect them from heat. This can help them withstand certain industrial processes. Other probiotics secrete sugars when cooled which enable them to survive freezing.'
Protech should result in new practical knowledge, particularly concerning industrial processes, ways of optimising them and how different bacteria react to them. These are all elements which should permit the development of the most effective products possible.
Safety and transparency
Modelling (in culture) of the crossing of the epithelial barrier of the intestinal wall by a pathogenic bacteria.
The benefits of probiotics should not cause us to forget their possible risks. 'Most of these organisms have been consumed for decades without any negative impact on health ever having been observed,' stresses Tiina Mattila-Sandholm. But an exhaustive scientific approach cannot allow matters to rest at that.
The Prosafe project was launched to focus exclusively on safety issues. It is looking into various problems, such as possible resistance to antibiotics, as well as the possibility of mutation, colonising capacities and the risk of poisoning. By the end of the study, the project aims, not only to have precise information on existing strains, but also to establish criteria and methods of investigating future strains that will emerge from laboratories.
The Proeuhealth project is also looking into public expectations, which vary from country to country, and the best ways of addressing them. Making the most of probiotics also means persuading people to consume them, usually on a regular basis for maximum effectiveness. That entails providing the general public with credible and comprehensive information on their benefits.
The Union has supported a series of food safety research projects. These have included investigations into mycotoxins (dangerous food contaminants secreted by mushrooms) and the development of biosensors capable of detecting the presence of toxins in ...
Probiotic foods are of major economic importance. According to a survey carried out in May 2001, the European market is worth over a billion euros and the figure is growing all the time. The US market, although smaller, is also growing and is a potential ...
Our knowledge of probiotics is not new. In 1907, the immunologist Ilya Metchnikoff first came up with the idea that the body's defences could be boosted by the absorption of fermentative bacteria. Nevertheless, it is only recently that researchers have ...
Tiina Mattila-Sandholm, Proeuhealth coordinator email
The Union has supported a series of food safety research projects. These have included investigations into mycotoxins (dangerous food contaminants secreted by mushrooms) and the development of biosensors capable of detecting the presence of toxins in meat or milk. A number of major research projects have also been carried out on BSE, particularly to develop tests which monitor the progress of the disease. The Sixth Framework Programme is further boosting this research effort with €685 million dedicated to Food Quality and Safety (Priority 5).
Probiotic foods are of major economic importance. According to a survey carried out in May 2001, the European market is worth over a billion euros and the figure is growing all the time. The US market, although smaller, is also growing and is a potential strategic target. Probiotics are already common currency in Japan where they are present in more than 50% of dairy products. They are generally found in yoghurts and other dairy products, but also in some soups, fruit and vegetable juices, and cereals.
Our knowledge of probiotics is not new. In 1907, the immunologist Ilya Metchnikoff first came up with the idea that the body's defences could be boosted by the absorption of fermentative bacteria. Nevertheless, it is only recently that researchers have started to show an interest in prebiotics, molecules which help beneficial micro-organisms to survive and function. These prebiotics are usually complex sugars, such as the insulin in chicory. They pass unchanged through the upper section of the digestive tract enabling them to interact with the bacteria in the intestines. A growing range of foods containing probiotics and prebiotics are now being tested with the aim of stimulating the bacterial effect. These mixed or symbiotic products would appear to have a promising future as researchers meet with growing success in achieving the delicate optimal balance between bacteria and protective molecules.