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Microorganisms have been part of the human diet for a very long time. They occur in large amounts in fermented foods in particular, and provide not only a particular taste, but also a longer shelf life. Milk is fermented with lactic acid bacteria to make yoghurt, kefir, sour milk, buttermilk and cheese. Vegetables and meat can be kept for longer periods using fermentation, which is how they were previously able to provide important nutrients also in winter or on long voyages at sea. In Germany, as well as in many of its neighbouring countries, sauerkraut is a particularly famous fermented product. However, it is not as widely known that this exceptionally valuable foodstuff was also known and cherished in Ancient Greece, the Roman Empire and China. The earliest references to fermented foodstuffs can be found in Sumerian wall paintings which were created around 2500 B.C. In a Persian version of the Old Testament, Abraham traces his long life back to the fact that he regularly consumes acidified milk.  As with the entire field of research of microbiology in general, the idea that bacteria can have a positive influence on human health is comparatively young. In his book, “The Prolongation of Life”, published in 1907, Ilya Ilyich Mechnikov, Vice-President at the Institut Pasteur—which is still famous to this day—and later Nobel Prize winner for physiology and medicine, published the theory that living lactic acid bacteria in yoghurt could suppress harmful bacteria in the gut. Today, such bacteria are called probiotics in accordance with the definition set by the former Federal Institute for Consumer Health Protection and Veterinary Medicine (BgVV): “Probiotics are selected living microorganisms which, when they reach the gut in sufficient amounts and in active form, generate positive health benefits.” However, don’t expect any probiotic effects from classic yoghurt and other sour milk products. The bacteria which grow in these are specialists at living in this medium, not in the human gut. The bacteria and yeasts which are used today in large-scale production are also selected based on whether their characteristics are ideally suited to the manufacturing conditions, while the natural gut bacteria on their part are highly specialised for the intestinal environment.  Probiotics must contain bacterial strains which can both survive contact with stomach acid and bile acid, as well as have a positive influence on the gut. These characteristics are not only typical of specific species of bacteria, such as Lactobacillus lactis, but are, above all, specific to the strain. This is why, when it comes to probiotic foods, great care is taken to ensure that only very specific bacterial strains are ever used; strains which are made up of identical cells with the same characteristics.
As bacteria were attributed to the plant kingdom for some time, the community of microorganisms which live in the gut is referred to as the “gut flora”. The correct term of “gut microbiota” or “intestinal microbiota” is now slowly becoming more established. This community includes at least 500 different types of bacteria; but we are far from having identified all of them. Some estimates even assume the existence of 15,000 – 36,000 types of bacteria.  We have a symbiotic relationship with our gut microbiota. This means that, as the host, we offer the bacteria a habitat while, on the other hand, these bacteria are essential for our health. They carry out very different functions within the body. It was only recently discovered that bacteria communicate with human cells via messenger substances and exchange information. [4-7]
Gut bacteria primarily feed off fibre, which is why it is so important to ensure that we consume a sufficient amount of fibre in our diets. The bacteria split the fibre and transform it into short-chain organic acids. In turn, these are used by the cells in the intestinal mucosa—the epithelium—to produce energy. The nourishment provided by our blood vessels is not enough when it comes to these cells. They depend on fibre intake and an intact gut flora. Should, as a result of intestinal operations, sections form in the gut which are cut off from the flow of nutrients, the bacteria cannot create any acids and the intestinal mucosa becomes inflamed as a result of a lack of energy (diversion colitis). Additionally, the acids formed by the gut bacteria improve the resorption of water and the absorption of certain minerals in the large intestine. They also have an influence on the smooth muscles of the large intestine and stimulate them to make the necessary movements.
What’s more, gut bacteria are able to break down some toxic substances and make them harmless, for example the carcinogenic group of substances known as nitrosamines, as well as polycyclic aromatic hydrocarbons. Bacteria also produce many vitamins, primarily vitamin B1, B2, B6, B12 and vitamin K. While the B vitamins are poorly absorbed by our bodies in the large intestine, the vitamin K which is produced there contributes towards providing nourishment to the individual, especially when too little vitamin K is taken in through the diet. 
The gut bacteria’s contribution towards fighting off pathogens is equally important; something which actually happens on multiple levels. The bacteria live on the protective film which lies on top of the intestinal mucosa. They form a barrier between pathogens which are ingested along with food and our gut, and strengthen the connections between the epithelial cells so that fewer pathogens are able to get through the gaps. What’s more, they secrete antibodies in response to foreign bacteria. In addition to this protective function, the gut microbiota also directly influences our immune system. The gut is an exceptionally important contact point for our body to the outside world. A large portion of our antibody-forming B cells can be found in the gut-associated lymphoid tissue (GALT). This means that an immune reaction can quickly be given against new pathogens which are ingested along with food, preventing infection. Thus, the gut is an important training centre for the immune system. The gut bacteria are essential for the maturing process of GALT in newborns and ensure that the body is able to protect itself from infections at a later date. [9, 10]
All of these functions carried out by the gut bacteria are essential for our bodies. Thus, a healthy gut microbiota is a prerequisite for a healthy body. In adults, the structure of the gut microbiota is very stable. However, it can still be influenced by some factors. This includes, of course, diet—especially when it is low in fibre or too high in protein or fats—as well as factors determined by the body itself, such as immune deficiencies, diabetes, stomach acid and bile acid, stress hormones and age. External influences include fungi, infections, the climate, intestinal operations, radiotherapy, as well as heavy metals, herbicides and fungicides from conventional agriculture. When the natural balance of the gut microbiota has been disrupted, special probiotics can have a positive effect.
While a baby is still in the womb, there are no bacteria in its gut. It is only once the baby is born that bacteria begin to colonise the gut. The first bacteria come from the mother or from the environment in the hospital. Over the first years of the child’s life, the composition of these gut bacteria changes until they have reached a balance which, in normal circumstances, remains stable. Using a supply of probiotic bacteria to colonise the gut only takes place in exceptional cases. Nor is this desired or necessary in order to make the positive effects of probiotics possible. Regularly ingesting probiotics ensures that the gut always has the necessary amount of bacteria available, thus enabling it to extend its beneficial influence. As the gut bacteria are much more complex than a simple active ingredient, they also have an extremely broad range of effects. Wide-ranging positive effects have been demonstrated through numerous studies over the past years; effects which shall be explained below.
Taking probiotics can mean that the symptoms associated with lactose intolerance—stomach pains, fatigue or difficulty concentrating—no longer occur. This is because probiotic bacteria are able to divide lactose in a manner similar to our natural lactase enzymes. In doing so, the lack of enzymes which causes the intolerance can be balanced out in a natural manner. 
When it comes to diets which are dominated by protein—something which has become more frequent since the emergence of the low-carb trend—the proteins can no longer be completely absorbed, which leads to some of these reaching the large intestine undigested. These are then broken down by various types of bacteria, which creates metabolic products which are harmful for our bodies, such as phenol, cresol, hydrogen sulphide and ammonia. This can be serious, particularly for people with liver or kidney failure. This is because, in these cases, ammonia can make it into the primary circulation system and damage the entire nervous system. This damage can be prevented effectively by increasing the body’s supply of fibre and probiotic bifidobacteria. With an increase in activity among healthy gut bacteria, the environment in the large intestine once again becomes slightly acidic. In doing so, ammonia exists in the form of ammonium ions, which can penetrate the cells of the gut in considerably smaller amounts. 
Triggered by the unfamiliar bacterial surroundings, traveller’s diarrhoea is the most common illness experienced when travelling by far. When it comes to journeys to Asia, Africa and South America, the sickness rate amounts to 50% of all holidaymakers who come from a temperate climate zone. Traveller’s diarrhoea is very unpleasant and often results in the traveller having to spend several days in bed. However, by taking probiotics shortly before and during the trip, the presence of supplied healthy gut bacteria prevents the harmful bacteria obtained from the surrounding environment from multiplying. In many cases, traveller’s diarrhoea can be avoided through this prophylaxis with probiotics, allowing for the holiday to be enjoyed in good health. 
Probiotics can also be helpful with problems on the other end of the scale, i.e. with constipation. This has been shown to be the case with chronic constipation which has no acute sources such as medication or metabolic disorders. Chronic constipation affects 5% of men and as many as 15% of women aged 25 and over. In studies, various strains—from E. coli Nissle to strains of Lactobacillus and Bifidobacterium—demonstrated positive effects and were able to alleviate chronic constipation and, in some cases, cure it completely. [13, 14]
Positive clinical study results have been achieved when it comes to irritable bowel syndrome and ulcerative colitis, an inflammation which primarily affects the mucosa of the large intestine. In cases of ulcerative colitis, probiotics were introduced alongside therapy and were able to considerably extend the time between the acute phases of inflammation—so-called “remission”.  To this day, we are yet to discover the causes of irritable bowel syndrome. Often, irritable bowel syndrome is a lasting result of inflammations of the gut and sometimes even other organs. Probiotics have been proven to have an influence on this disorder. They have been shown to improve individual symptoms—alleviating pain in particular. 
Due to the close link between gut microbiota and the human immune system, probiotics can strengthen our natural defences. Probiotics can be used not only prophylactically to prevent diarrhoea—such as in the case of traveller’s diarrhoea—but can also be used as a successful method with which to treat a diarrhoea-based illness after this has already broken out [17, 18]. A protective effect has also been demonstrated in the case of colds. In one study, the duration and severity of the time spent with a cold and the number of days with a fever during the three winter months was able to be reduced through administering probiotics. [19, 20]
A very recent study on hay fever patients demonstrates that the gut bacteria’s influence on the immune system is not only one which strengthens it, but also one which can regulate it. Allergies occur when an immune response is triggered in response to harmless factors such as pollen. This overreaction can be reduced via probiotics. In the study, the eye problems associated with a pollen allergy were able to be reduced, and the general well-being of the patients improved as a result of the probiotics. 
When viewed as a whole, the gut microbiota have an exceptionally major influence on whether we are healthy and whether we feel at ease. It is very important to provide them with fibre through our diets and, where necessary, to support them with probiotic bacteria.
The positive effect of probiotics has been well researched. However, to date, no health claims have yet been approved for dietary supplements with probiotic bacteria. This is mainly due to the fact that, when it comes to health claims, particular consideration is given to avoiding making reference to illnesses and thus to strictly differentiate dietary supplements from pharmaceutical products. Therefore, in order to support a health claim, a study must have been carried out exclusively on healthy, adult test subjects who were investigated according to very specific parameters. As the studies which have been carried out until now were not specially aimed at fulfilling the criteria of the EFSA, a successful application for a health claim is yet to have been made. However, this issue is being discussed in-depth with the EFSA. Subsequently, various guidelines with exact definitions for bodily functions, risk factors and even disease end-products have already been determined, which can be referred to to substantiate health claims. This has made the planning of studies considerably easier and we should be able to expect new, successful applications for health claims with probiotics in the future.
However, the health-promoting effect of probiotics or intestinal microbiota has since become general knowledge among end consumers, meaning that probiotics products are being bought more for their active ingredients—the health-promoting bacterial strains—than due to any health-related statements on the packaging.
Dr. Susanne Kühnl
is the Projects and Development Manager at Goerlich Pharma GmbH. She completed her studies in food chemistry at the Technical University of Munich and will soon be completing her PhD at the University of Innsbruck on the subject of new anti-inflammatory and immunomodulating natural substances. During this time, she has taken part in numerous international conferences on this subject, including the DNTI Symposium – Drugs from Nature Targeting Inflammation.
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