"The Digestive Contract of Friendly Bacteria & Gut Health"

Lennart Cedgård MD and CEO Wasa Medicals, Halmstad, Sweden

Introduction

Probiotics have been defined as a live microbial feed supplement that beneficially influences the health of the host by improving the intestinal microflora.  The use of probiotic bacteria in therapy is not a new invention. Yoghurt, containing probiotic bacteria have for hundreds of years been appreciated for its health bringing properties. Today, research is ongoing throughout the world to clarify the mechanism of probiotics. Intake of probiotic bacteria have many positive effects on health like increasing the digestion and absorption of nutrients, improvement of intestinal lactose digestion, improving the intestinal milieu, regulating the gut motility, stimulating the immune system, prevention of cancer, reduction of catabolic products eliminated by kidney and liver etc.

The concepts of Metchnikoff are thus finally being confirmed both experimentally and clinically. Metchnikoff (1845-1916) claimed in his theory of longevity that intake of yoghurt decreases the toxic effect of the colonic flora by inhibiting the growth of putrefactive bacteria in the large intestine. He further claimed that the toxic products produced by putrefactive bacteria are the cause of many ageing processes in our body and that the long life of Bulgarian peasants resulted from their consumption of fermented milk products. Continuous conditioning of the intestinal ecosystem is useful in medicine and should be routine care, particularly in aged individuals.

Why is there a need of probiotic bacteria today?

In modern times, we have dramatically changed the composition of bacteria entering our body via food and drinks. The intake of bacteria, preferably Lactobacillus species is highly reduced. In former times, fermentation was one of the main ways of preserving food, vegetables and dairy products. This assured a constant intake of lactic acid-producing bacteria. Today the situation has changed. Use of freezers, refrigerators and pasteurisation of feeds like dairy products and the use of different kinds of preservatives have replaced fermentation as a method for preservation of food. Today, most people do not get probiotic bacteria via the food in the same amount as in former times. As a matter of fact we get 2g faeces every day without knowing via contamination and by inhalation!

Uses of antibiotics in healthcare and agriculture, and the increased hygienic measures in modern society with antibacterial substances in cleaning agents, toothpaste, deodorants etc., have decreased the amount of total bacteria in our environment. Studies have shown differences between the intestinal microflora of people in developed and developing countries, both in infants (2) (3) and adults (26). In developing countries, people have a more varied intestinal microflora with more strains and a higher turn - over of bacteria. In Western industrialised countries we have relatively few strains in the intestinal flora and we keep the same strains for longer periods maybe years. A high turn - over of bacteria is certainly very important in keeping the immune system stimulated (39).

 On top of this, we have today an increased interference on the bacterial ecosystem in our body compared to previous times, via a changed diet (rich in protein, fat and refined products like sugar and poor in fibres), stress, increased intake of medicines like antibiotics, and environmental toxins etc. The need of probiotic bacteria is thus due to the many factors in our society that can damage the intestinal health and the fact that the intake of probiotic bacteria via the food has decreased. A healthy intestinal milieu is crucial for our health.

We have since the discovery of bacteria and the invention of antibiotics had the general idea that the major part of the microbes are pathogenic but it is in fact only a minor part of the thousand of bacterial species that are harmful to the humans.

The intestinal microflora.

There is a whole world of "microlife" in our intestines. The normal intestinal microflora build up a fantastic ecosystem, which is extremely complex and impossible to understand completely. What we know today is that our intestinal microflora consists of about E14 cells, which is ten times the number of human cells in our body. The normal microflora, sometimes called the biggest “organ” in the body has a weight of approximately 0,5-1,0 kg and at present it is estimated to consist of 1000 different species. However, recent genetic research shows that, when mapping the genome of the colonic bacteria only 35 per cent in previous times were to be identified and assigned to known bacteria. The remainder were unknown! We know today that the amount intestinal viruses are 10 times that of bacteria still to be defined.

 

The stomach and the upper part of the small intestine contain low counts of bacteria (E3–5/ml gastric juice) due to the gastric- and bile acid. Further down in the small intestine the number of bacteria increase to E6-7 and in the colon the counts are as high as E11/g faeces.

 

The intestinal microflora consists of both aerobic bacteria, which need oxygen to survive, and anaerobic bacteria that will die in the presence of oxygen. There are also facultative anaerobic bacteria, which can live, in both aerobic and anaerobic milieus.

Immediately after birth, bacteria start colonising the skin and the mucosal membranes like the respiratory tract and the intestine. During the first days of life the milieu in the intestine is rich in oxygen. Therefore the first colonisers are aerobic and facultative anaerobic bacteria like E.coli and other Enterobacteriaceae, Enterococcus spp and Staphylococcus spp.  (6) (7) (36). When these bacteria start proliferating they consume oxygen so the intestinal milieu will become more and more anaerobic, which in turn makes it possible for anaerobic bacteria like Bacteroides, Bifidobacterium, Clostridium and Lactobacillus to start colonising. Within a few days anaerobic bacteria will dominate the intestinal microflora of the infant and in adults more than 99% of the bacteria in the intestine are anaerobic. The intestinal microflora of infants are much simpler and much more liable to fluctuate than the one of the adults, which is generally very “stable”. During the weaning period the infants' bacterial flora starts to resemble the one of the adult but may not be fully developed until 4-8 years of age.

 

The dominant species in colon of an adult are Bacteroides and Bifidobacterium whereas Lactobacillus spp. and Streptococcus spp. dominate the small intestinal microflora. It is possible that the flora in the proximal parts of the gastrointestinal tract, though quantitatively much smaller than that in the colon, is most important since its products pass the absorptive part of the intestine. The bacteria in the small intestine may also have the strongest influence on the immune system since the gut-associated-lymphoid-tissue (GALT) is situated mainly in the small intestinal wall estimated to contain approximately 80% of the total immune system.

 

Some bacteria are said to be colonising, which means that they are able to colonise, proliferate and remain in the intestine for longer periods, weeks, months or years. Other bacteria are referred to as transient. These bacteria enter the gastrointestinal tract via food or drinks and are in transit from the mouth to the anus. Most probiotics are transient even if said to be colonizing as they remain in the colon up to 2 weeks after intake.

 

The habitats of the normal bacterial flora in the intestine are shredded intestinal cells or food particles, the mucosa, or rather the overlying mucous layer and the Lieberkühn's crypts. The crypts have shown to contain a very specific flora, often consisting of a single species. Both the crypt flora and the mucosal flora may be physiologically important but not reflected in faecal cultures. Another fact to consider is that the cell turnover may be great although the culture counts are not impressive.

 

Even though, the intestinal flora of adults is considered as stable as to the composition of species, new strains are entering the intestinal tract all the time via food and beverages or in other way swallowed and other strains leave via the faeces. Thus, there is a constant turnover of bacteria in the intestine, which is very important for the stimulation of the immune system.

In  1972 van der Waaij introduced the term “competitive colonisation” which describes the interference between the normal intestinal microflora and the invading pathogens. By competing about nutrients and space and by secretion of antibacterial substances the normal intestinal microflora can prevent pathogenic bacteria from colonising. In germ free animals only 10-100 salmonella bacteria is needed for infection to occur while in a conventional animal it takes 1.000.000 bacteria. The prerequisite for a bacterial infection to occur is that the normal microflora is disturbed. The Terrain is decisive!


The intestinal ecology is vital in both in the genesis, prevention and treatment of disease.

The small intestine and the immune system

The mucosal membrane of the intestine, which has an area of around 200m2, is under constant challenge by different kinds of antigens. Not only do we swallow food antigens (60-70 tons throughout a lifetime) and food-borne microbes, but also inhaled particles that become trapped in the respiratory tract and transported up to pharynx are finally swallowed and reach the intestine. Furthermore, the mucosal membrane of the intestine has intimate contact with the normal intestinal microflora.  It is therefore not surprising that the intestine contains the largest accumulation of lymphoid tissues in the body. Eighty per cent (!) of the lymphocytes in the body are situated in the intestinal wall, in the so-called gut-associated-lymphoid-tissue (GALT). They appear as aggregates in lymph nodules called Peyer's patches and as scattered lymphoid cells in the lamina propria. Further, the intestinal epithelia are seeded by small lymphocytes termed intraepithelial lymphocytes.

The GALT is associated with the rest of the lymphatic system via lymphatic vessels directed toward lymph nodules situated in the mesenteric fibrous tissue that lines the small intestine.

The immune system has two major functions, equally important: to react on foreign, dangerous antigens and particles like pathogenic bacteria and viruses and to not react on harmless antigens like food antigen and body tissue. These two functions have shown to be associated with each other.

Intestinal immune responses to bacteria are mainly induced in the Peyer's patches. When lymphocytes (B- and T-cells) in the Peyer's patches are activated by bacterial antigens they start proliferate and leave the intestinal tissue for the blood. They circulate during a couple of days before they settle down somewhere in the mucosa-associated-lymphoid-tissue (MALT) (10) (31) (16), which is the lymphoid tissue associated with all the mucosal membranes in the body like the intestinal, respiratory and uro-genital mucosa. Lymphoid tissues of all the mucosal membranes in the body are in this way interconnected. Immunological reactions, like allergic reactions in the intestine are likely to influence the status of other mucosal tissues. When the activated B-cells have settled down they mature and start producing IgA antibodies. Thus, the bacteria induce immunity against themselves. The paradox is that at the same time as the bacteria induce strong immunological reactions against themselves they decrease immunological reactivity against other antigens like food antigens. The mechanism of this is not completely known, but studies have shown that it is difficult to achieve oral tolerance in animals lacking an intestinal microflora (28) (42) while administration of bacterial antigens with the food increases the tolerating affect of feeding (20). Conversely some bacterial toxins like cholera toxin may break oral tolerance to food antigens (12) so the composition of the intestinal flora is of importance.

Further, studies points to the importance of a high-turn over of bacteria for the stimulation of the immune system. It is important that the immune system meet with new bacterial antigens continuously. As soon as IgA antibodies are produced against a certain bacterial antigen, antibodies bind to the antigen and inhibit it from translocating the intestinal wall and reach the Peyer's patches (39). The low turn-over of bacteria and the decreased number of bacterial strains in the intestinal microflora of people in the western world may lead to a decreased bacterial stimulation of the immune system which could lead to over-reactivity against other antigens like food antigens.

The immune system of an infant is not fully developed. The intestinal barrier is immature and the capacity to generate IgA-producing cells is inadequate.  Bacterial colonisation provides maturational signals to the GALT (17). Thus, the intestinal microflora is important for the maturation of the immune system in infants. Animals lacking an intestinal microflora have very small Peyer's patches, the level of IgA antibodies in blood is low and the amount of T-cells in the intestinal wall is also decreased.

General aspects of probiotics

Probiotics has been defined as live microbial feed supplement that beneficially affects the host by improving the intestinal bacterial balance. Bacterial species commonly referred to as probiotic are lactic-acid producing bacteria such as Bifidobacterium spp., Lactobacillus spp. and Streptococcus spp., but also other micro-organisms like the fungi S. boulardii have been used. There are many properties of probiotic bacteria that may help to improve the intestinal milieu like their metabolism, cell-wall structures and intracellular components.

Suggested beneficial effect of probiotics:

  • Increased nutritional value (better digestibility, increased absorption of minerals and vitamins).
  • Promotion of intestinal lactose digestion.
  • Positive influence on the intestinal microflora (antibiotics or radiation induced colitis).
  • Prevention of intestinal tract infections (bacteria or virus induced, Candida enteritis, Helicobacter pylori ulcers/neoplasia).
  • Regulation of gut motility.
  • Improvement of the immune system
  • Prevention of cancer.
  • Reduction of catabolic products eliminated by kidney and liver.
  • Prevention of atherosclerosis by the reduction of inflammation!
  • Prevention of osteoporosis.
  • Improved wellbeing.        (11)

 

Lactic-acid-producing bacteria metabolise nutrients by fermentation. During this process different organic acids are formed like (L+) lactic acid and butyric acid, which lowers the intestinal pH. The lowered pH has many beneficial effects on the intestinal milieu like inhibiting growth of putrefactive bacteria. Putrefactive bacteria produce nitrogen waste products during digestion of nutrients. The benefits of inhibiting growth of these bacteria are the reduction of blood ammonia, free serum phenols and free amino acids in the urine. This implies improved nitrogen retention. These characteristics could be responsible for the growth and improved body weight (muscle volume) seen in different animal studies. Reduced concentration of nitrogen related toxins play an important role in the detoxification of the liver. Uric acid, the natural antioxidant produced in the liver as a response to excess amounts of free radicals, is related to the level of dysbiosis in the intestinal tract. This explains why probiotics will stimulate liver regeneration and subsequently would be used in a "liver support program".

 

It is often claimed that a probiotic culture has to be able to adhere to the intestinal epithelia and colonise the intestine to have any effect. This issue is controversial. First of all, what is the definition of a “colonising bacteria”? Colonising bacteria are sometimes referred to bacteria that are more permanently found in an individuals flora but in other cases bacteria remaining in the intestinal flora for 1-3 days are considered as colonising (15). In constipated people transient bacteria can probably be found in faeces for longer periods than three days.

A method, often used to test bacteria's ability to colonise in the intestine is to see if they adhere to intestinal epithelial cells in vitro.  This is not a fully adequate way of looking at colonisation ability since there are other habitats for colonising bacteria than the epithelia like the overlying mucosal layer and loose particles. Thus, bacteria with negative results in the test mentioned may anyway be able to colonise. Ninety-nine per cent of the intestinal microflora consists of anaerobic bacteria, which means that they die in the presence of oxygen. The area closest to the epithelia is probably not the preferable habitat for these bacteria since oxygen diffuses from underlying blood vessels to the epithelial cells and than to the supraepitelial area. This supports the fact that bacteria must not be able to adhere to the intestinal epithelia to be able to colonise.

Lactobacillus GG have shown to reduce traveller’s diarrhoea, antibiotic-associated diarrhoea and relapsing Clostridium difficile colitis even though only “colonizing” for 1-3 or 7 days, which would be considered as transient.

Bacterial strains regarded as transient can certainly also have effect when administered in high counts by interaction with the immune system and by improving the intestinal environment, stimulating growth of the normal bacterial flora.

Nutritional aspects of probiotics

All mineral- and vitamin substitution will demand a healthy intestinal ecosystem. The microflora must be in a good shape and in balance for the nutritional system to be able to effectively utilising minerals and vitamins. This is often not the case. The metabolism of proteins, lipids and carbohydrates will be improved if the bacterial flora is balanced. The endocrine, the immune and the nutritional system are dependent of that both the external and the internal ecology are in balance.

Daily supplementation of friendly bacteria, probiotics is needed to replace the bacteria we are supposed to get and that we did get earlier via the food but is deficient today due to modern technique of preserving food.

All mineral- and vitamin supplementation demands a healthy intestinal ecosystem.

Bacteria consume vitamins. When there is an overgrowth of colonic bacteria in the small intestine the loss of vitamins due to bacterial consumption can be remarkable and lead to vitamin deficiency. Probiotic bacteria inhibit overgrowth of colonic bacteria in the small intestine and therefore reduce the loss of vitamins. Compare to imbalances in spite of additional intake of vitamins.

An improved effect on the mineral absorption due to:

  • Osmotic effects
  • Increased production of organic acids due to fermentation
  • Increased formation of soluble salts of these acids
  • Proliferation of the intestinal wall

 

Enzyme induction or enzyme support will improve the absorption of nutrients.

The stimulated bifidobacteria increase the production of the vitamins B1, B2, B3, B6, B7, B9 and B12. These vitamins are absorbed by the intestine and utilised by the different tissues of the human body.

Reduced production of toxins or so-called free radicals, which consumes vitamins, minerals and antioxidants.

To be noted: most production of free radicals is to be seen in the intestine. This will increase if the microflora is dysbiotic. Bifidobacteria and lactobacilli produce organic acids, which will work as antioxidatives. Studies by Kaizu et. al. (19) shows that there is a reduction of app. 70% of the oxidative activity in the intestine during supplementation of lactic-acid producing bacteria, which also implied a better status of vitamin E (35).

Immunological aspects of probiotics

Probiotics has been defined as live microbial feed supplement that beneficially affects the host by improving the intestinal bacterial balance.  Probiotics have a balancing effect on the immune system, both the innate and specific immunity. It is though important to notice that different probiotic bacteria may elicit different kinds of immunological responses, differently strong.  The administration route of bacteria is also important to consider when testing the immunological response to probiotics. Many bacterial species are compromised or damaged during the pathway through the stomach and upper small intestine. Using acid and bile acid resistant strains and by using protective tableting matrix technique assures that the main part of the supplemented bacteria reach the intestine and can be immunologically active.

The normal intestinal microflora is part of the innate immune system. By  "competitive colonisation" (43) commensal bacteria inhibit pathogenic bacteria from colonising the mucosal tissue, which is the initial step of infection. Probiotic bacteria inhibit colonisation of pathogens by producing organic acids like lactic acid and butyric acid, which lowers the intestinal pH and in that way inhibit growth of potentially pathogenic microorganisms. They also produce other bactericides that inhibit growth of certain bacteria. Competition about nutrients and space are also involved in the term competitive colonisation. The antimicrobial activity of probiotic bacteria explains the usefulness of such bacteria for conservation of food.

Regarding the influence of probiotics on the cell-mediated immunity, research have shown that intake of probiotic bacteria increase the production of IgA antibodies (18) (32) (27) (44) increase the activity of macrophages and NK-cells (34) (33) (5), which leads to an increased killing of bacteria. It has also been shown that probiotic bacteria modulate the cytokine activity. Cytokines are signal substances in the immune system, which regulates the activity of the immune cells. Probiotics stimulates the immune system in an “anti-allergic” direction with decreased production of IgE antibodies as a result (25). Cytokines also work as a link between the immune system and the nervous system.

 

The intestinal barrier

The mucosa of the intestines is a selective barrier which, when functioning normally, prevents the penetration of potentially noxious agents into the bloodstream, while still enabling the passage of useful substances, such as nutrients. The health of the intestinal wall is totally crucial for our health.

Probiotic bacteria have a healing effect on the intestinal mucosal membrane by stimulation of the formation of epithelial cells and by decreasing inflammation in the intestine, shown by a decreased production of inflammatory cytokines during intake of probiotic bacteria (22). A prerequisite for development of allergy is that substances that in normal cases do not pass the intestinal barrier leak out into the blood and come in touch with the immune system. It has been shown that atopic eczema is associated with intestinal inflammation and increased antigen transfer over the intestinal barrier (23). Treatment of food-allergies with probiotics has shown to have positive effect (22).

 

Technical aspects of probiotics

As I have been involved many years in the field of intestinal micro-ecology, my interest in how to develop probiotics has increased. There are some objectives that are to be looked upon if to create an "optimal performance" probiotic product.

 

The choice of bacterial cultures

Would it be best with just one single strain culture or a mixture of different cultures? Some advocate that a multi-strain product is positive, due to that there are different beneficial characteristics in the different cultures that will be added to each other. The performance of the different cultures could thus be synergistic (30) but this is not always the case as the more different strains introduced the more competition, which could inhibit the activities for the superior probiotic strains! It is also more difficult to achieve high standards of quality control in multi-strain products. Single strain probiotics may be so far a little easier to document. As probiotic strains are transient the diversity of the innate flora would not be influenced whatever amount of strains included in the probiotic product.

 

Quality and stability

Freeze dried cultures are to be preferred and tablets produced by a low-compression method as ProBion with its ingenious matrix have a better stability and sustainability compared with capsules.

 

Administration and packaging

The freeze - dried powders would be packaged in an optimal form. To administer the powder itself directly into the gastrointestinal system is not particularly cost effective. This is due to heavy loss of bacteria caused by the bactericidal effect of the bile acid and to a lesser degree of the gastric acid. Choosing acid tolerating and bile-acid-resistant cultures could reduce these losses. Another way is to encapsulate the powder into gelatine capsules. The stability of the cultures is however influenced by the moisture content (5-10 %)! in these capsules.

Therefore many attempts have been made during the last years to produce tablets. This is however quite difficult due to the compression forces that the bacterial cells will experience during the formation of tablets.

 

In the company Wasa Medicals, where I am engaged, a new method of making tablets with viable cultures has been developed. This is a low compression method, which minimise the splint forces as compared to conventional methods.  The products benefiting from this technique are now introduced to the market.

 

Background.

Tablets made with conventional methods will damage the cultures due to splint and compression forces. Capsules contain 10% moisture, which is detrimental to the cultures. This implies poor stability and viability. With powders administered in sachets or similar, it is difficult to conduct the dissolution and disintegration in the gastrointestinal tract and this will therefore reduce the effect of the cultures. Tablets with controlled disintegration give better delivery and research shows that customers (85%) prefer them.

 

Technology.

The method of tableting has the advantage of promoting and improving the quality and the effect of the cultures, since it involves less compression, less split forces and reduced heat development. The cultures are protected in clusters formed during compression. This supports good viability and stability. The tablet makes it possible to conduct dissolution of the cultures in the gut, activating them properly in the right place and thereby achieving an optimal biological effect. The innovation involves the use of fructooligo- and polysaccharides. These are also defined as prebiotics and work in synergy with the probiotic cultures - synbiotics!

 

Probiotics must be seen as the primary food supplement.

 

ProBion is by definition probiotics + prebiotics = synbiotics, i.e. health promoting transient biocultures with influence on the gastrointestinal ecology. The probiotics work mainly through the substrate that the culture itself represents. As a complement to the probiotic cultures inulin acts as a substrate to the bifidobacteria. These, metabolic fibres, are considered prebiotics and contains fructooligosaccarides and  fructopolysaccharides (FOS and FPS). They promote and stimulate the activities of the bifidobacteria and thus they are called bifidogenic.

Safety of probiotics

Probiotic cultures are “generally recognised as safe” (GRAS). No case of infection has until now been traced to food-borne lactic acid-producing bacteria (1). However, theoretically all bacteria can become pathogens depending on the immunological status of the host so the safety of probiotic supplementation ought to be discussed.

Rare cases of local or systemic infections due to bifidobacteria, lactobacilli or other lactic acid-producing strains have been reported (13) (4) (14). In these cases a severe disease, like cancer or AIDS afflicted nearly all patients and most important, the infecting organism appeared to come from the patient's own microflora.  In two Finnish studies 9229 blood samples were cultured and the isolates were compared with dairy strains. Twenty samples contained lactobacilli, but none were identical to any of the commercial strains (38) (37).

Theoretically, digestive lesions or immunodeficiency could increase the risk of infection caused by probiotic bacteria. However, S. boulardii a fungal probiotic have been given to patients with Chrohn's disease, enteritis and AIDS and no cases of infection were reported in these patients. L. rhamnosus strain GG has been given to premature babies and patients with Crohn's disease with no side effect reported.

Administration of probiotics have shown no immunological side effects like fever, arthritis or autoimmune diseases except for one case of autoimmune hepatitis that might have been enhanced by ingestion of large doses of yoghurt (9).

Diseases due to deleterious metabolic effects of probiotics have never been reported. Supplementation of probiotics highly increases the number of bacteria in the small intestine, which could increase the deconjungation and dehydroxylation of bile acids to toxic, free secondary bile - salts. The biological effect of this has though shown to be minimal (24) and it should not be considered as a dangerous side effect of the tested probiotic product.

Some probiotic bacteria have the ability to degrade mucus, which theoretically could harm the mucosal membrane of the intestine. A study of the mucous degrading effect of L.acidophilus, Bifidobacterium spp and L. rhamnosus showed no effect in vitro or in gnotobiotic rats mono-associated with the strain.

Finally, the questions of gene transfer. Antibiotic resistance genes, especially those carried by plasmids can be transferred between microorganisms. The question is weather antibiotic resistance genes may be transferred between probiotic bacteria to pathogens and render them antibiotic resistant. It is well known that resistance to vancomycin can be transferred among E. faecium, which makes it important to investigate the safety of this strain.  Some lactobacilli strain like L. casei, L. rhamnosus, and L. plantarum are also resistant to vancomycin, but the resistance genes are chromosomally encoded and not transferable to pathogenic species. In conclusion the antibiotic resistance profile does not appear to be a real problem of a probiotic exception for plasmid encoded antibiotic resistance like in E. faecium. It is important to emphasise the great value of supplementation with probiotics during antibiotic treatment in the prevention of Clostridia difficile diarrhoea and other complications associated with antibiotic treatment.

Clinical aspects of probiotics

As we have been working with many different patients during the last 10 years, there are a great number of stories to be told.

 

In general people with disturbances from the gastrointestinal tract react very positive on ProBion supplementation. What we often call a "stressed stomach", respond quite well after being administered ProBion. Loose stools become normalised and constipated individuals suddenly experience a normalised defecation pattern i.e. 1-3 times daily. It is important to consider that initially, when beginning with probiotics, symptoms of unbalanced flora will be pronounced. This implies a slow and soft approach in most cases. Otherwise the individual could interpret these aggravations incorrectly. The more of adjustment you need, the more possible it is that these initiation symptoms will arise. These symptoms could be of any kind. They are related to the symptoms that are related to the dysbiosis itself, see all case reports beneath.

Certain conditions when probiotics are of importance

Neurogenic diseases

Spinal muscular atrophy also called SMA. This is genetic dependent disease amongst small children. Already in the first year of life, these children will be affected by an increasing atrophy of their nerve cells in the spinal cord. Their muscular capacity is markedly reduced. The disease is somewhat similar to the more well known Amyotrophic lateral sclerosis also called ALS. A father, who told me that after about 7-10 days of ProBion supplementation his child converted and started to stand up and walk, once contacted me. This was something that he had not been able to do for months. Withdrawing the ProBion led to his earlier condition after a week. The procedure was repeated with the same manifestation! There certainly is a link between the microflora in the intestine and the immune system and the nervous system. What really happens is still to be explored.

 

Gastritis and ventricle ulcer, dyspepsia

These people respond quite quickly and they are therefore very grateful to treatment.

 

Constipation or colon irritabile

Together with an adequate adjustment of the diet, these people need to start slowly with probiotics to achieve their objectives. Good results.       

 

Migraine; conversion of tyrosine to tyrosamine

If related to diet there is an excellent effect.

 

Atopies i.e. eczema, hay fever, urticaria and asthma   

Allergies are very complex immunological dysbalances. Probiotic approach will often give positive results. Allergies are often connected with a leaky gut, which leads to increased passage of potential allergens over the intestinal wall. Probiotics have a healing effect on the intestinal epithelium, which is beneficial in the treatment of allergies. However, asthma is a severe condition and usually takes longer time to cure. A change in diet is often needed.

 

Food intolerance e.g. gluten intolerance, lactose intolerance

If acquired by the use of antibiotics or other dysbiotic factors, these conditions often regress and vanish after a correct probiotic administration. Probiotic bacteria improve lactose digestion and increase the enzyme activity in the intestine, which is an important step in preventing food allergies. Studies and practise have shown good results in these cases.                       

Chronic inflammatory diseases or autoimmune diseases such as rheumatism, SLE, fibromyalgia, colitis ulcerosa and Mb.Crohn

As being related to a dysfunction in the immune system, adjusting the balance in the intestinal flora will give a good support in the recovery from the diseases.

 

Infections in the genito-urinary system

Recidives of chronic infections are often related to a dysbiosis. When taking the ProBion there are many reports of reduced frequency or a total regression.

 

Mycosis i.e. Candida albicans

As being the top of the dysbiotic pyramid, this condition is corrected together with an adequate diet.

 

Exposition to radiation, cortisone, antibiotics and contraceptives

These ecological stress factors must be supported with probiotics, if to reduce the side- effects of these therapies.

 

Conditions with impaired immune defence i.e. malignant disease

These conditions need the support of probiotics.

 

Insufficiency of vitamins or minerals

All therapies with a nutritional impact must be supported by effective probiotics to increase the uptake of nutrients supplemented.

 

Stress

Maybe this is the most common condition. The need to adjust behaviour would naturally be supported by probiotics.

 

Skin diseases e.g. acne and herpes

The dysfunction of the endocrine system is often related to the intestinal flora. Herpetic infections are more complicated due to the intracellular nervous manifestation. Though these may respond as the outbreak of herpetic blisters is influenced of the general condition of the immune system.

 

Hormonal dysfunction i.e. bleedings, menstruation dysfunction, infertility and osteoporosis

As the hormonal balance in the body is influenced by the intestinal flora via the entero-hepatic linkage, problems of these natures could be adjusted by probiotic administration.

 

Metabolic syndrome and diabetes

There is a relation to the intestinal flora and to what you eat. Food with hyperglycaemic characteristics will influence both the flora and the conditions themselves. There are some reports indicating that some strains in the flora are able to produce insulin analogues. These may interfere with the normal insulin performance. It could even be a factor responsible to the development of insulin resistance!

   

Chronic fatigue syndrome

Antibodies against the intracellular mitochondria are found to be of intestinal origin! These are thought to be responsible for this condition.

 

Atherosclerosis

As we today understand chronic inflammation triggered by dysbiotic conditions in the gastrointestinal tract initiates many of the health disorders connected with modern life style.

 

 

Diarrhoea.

Products of microbial metabolism of dietary foodstuffs may also cause alterations of the mucosa. Such bacterial end products may be responsible for the diarrhoea and the colic, which often accompany small bowel contamination.

The use of antibiotics is known to result in massive disturbances of the intestinal flora composition, often with long lasting negative effects including overgrowth by E. coli or other potential pathogens with resultant septicaemia and endotoxemia. Diarrhoea thus is a common manifestation with patients receiving antibiotic therapy

Everyday stress situations can also cause alterations in the quantity and composition of lactic-acid producing flora in the gastrointestinal tract. Diarrhoea frequently accompanies periods of nervous tension. This neurogenic diarrhoea is caused by excessive stimulation of the parasympathetic nervous system that greatly excites both motility and secretion of mucus into the colon.

 

Supplementation of probiotic bacteria has shown to decrease diarrhoea during antibiotic treatment (41) and improve the health of children with persistent diarrhoea (8).

 

Dysbiosis in man under extreme conditions was investigated (21). It was shown that Yoghurt and other types of lactobacilli containing products could be used with success in order to minimise the disturbances caused in cosmonauts by the stress situations in long-term and short-term flights in space.

 

Neumeister (29) investigated the variations of normal bacterial flora in the small intestine during and after irradiation therapy in 500 patients with cancer. In order to eliminate some of the disturbances, 162 patients were administered orally a mixture of flora culture isolated from healthy human intestine and consisting of non-pathogenic E. coli, L. acidophilus and B. bifidus, and pancreatic enzymes. The bacterial treatment was started at the same time as the X-ray treatment and continued during the whole treatment. Using X-ray therapy and supplementation with the lactobacilli preparation, the frequency of diarrhoea and other side reactions decreased from 61 to 12 % and in cobalt therapy from 79 to 21 % which values are highly significant.

 

In gastro-enteritis where it can be an infection at any point of the gastrointestinal tract, in infectious diarrhoea, the infection is most extensive in the large intestine. At any point of infection in the intestine, the mucosa becomes extensively irritated, and therefore its rate of secretion is enhanced. The motility of the intestinal wall is increased and large quantities of fluids are made available for washing the infectious agent toward the anus with strong peristaltic waves. This is an important mechanism for ridding the intestinal tract of the debilitating infection. Lactobacilli can reverse this state, calm down the irritation of the mucosa and thus minimise the disturbance and diarrhoea.

In ulcerative colitis where also extensive areas of the intestinal wall of the large intestine is irritated and ulcerative, the motility is often increased as much as 10-fold, and the patient has repeated diarrheal bowel movements. During this state there is an impaired absorption of nutrients and a massive loss of fluids and electrolytes and thus a vicious circle for the patient.

 

 Both during everyday stress and during extreme stress situations as well as infections the additional Yoghurt intake with large amounts of viable lactobacilli may prove as beneficial in preventing and curing gastrointestinal disturbances (40).

 

Some final comments

A quite new field in science is called psycho-neuro-immunology, which is the study over the interaction between psychological factors, the nervous system and the immune system. Since the intestinal microflora has such a strong influence on the immune system and also interacts with the hormonal system it could be said that there is a psycho-neuro-immuno-endocrino-intestinal-microbiological linkage. In other words, all systems in the body are connected and a “holistic thinking” is necessary in medicine.

 

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