Probiotics: Functions

With the experimental and clinical studies currently available, it can be demonstrated that probiotics are capable of the following beneficial effects:

  • Promotion or maintenance of optimal intestinal flora.
  • Prevention of colonization of pathogenic germs in the intestine and the passage of pathogenic bacteria through the intestinal wall (translocation).
  • Formation of the short-chain fatty acid butyrate, which is the main source of energy of intestinal cells. It is considered an important factor in maintaining human health, as it strengthens the intestinal epithelium and stabilizes local immune defenses.
  • Strengthening immunological defense mechanisms
  • Prevention of intestinal and vaginal infections
  • Lower frequency, shorten the duration and reduce the severity of various diarrheal diseases.
  • Improvement in symptoms of irritable colon (irritable bowel syndrome).
  • Increase motility of the intestine, relieve constipation (constipation) and flatulence (flatulence).
  • Reduction in the risk of allergies and autoimmune diseases.
  • Inhibition of carcinogenesis (cancer development) in the colon (large intestine).
  • Lowering cholesterol levels – avoiding hypercholesterolemia -, influencing lipid metabolism.
  • Alleviation of symptoms of lactose intolerance and improvement of lactose digestion in malabsorption.
  • Delay the aging process
  • Prevention and treatment of diverticulosis and diverticulitis.
  • Positive influence on radiation therapies
  • Protection against neurodermatitis
  • Potential effect in hepatic encephalopathy and renal insufficiency (kidney weakness).
  • Biosynthesis of vitamins such as vitamin B12, vitamin B6 (biotin) or vitamin K1.
  • Increase mineral absorption, especially calcium.
  • Osteoporosis prevention
  • Metabolism of xenobiotics (chemical compounds foreign to the biological metabolic cycle of an organism or natural ecosystems).

In addition to the protective effects on health, probiotic lactic acid bacteria also guarantee the shelf life of the fermented food. The acids formed during fermentation by the bacteria and other microbial inhibitors have a growth-inhibiting effect on undesirable germs.

Promotion or maintenance of optimal intestinal flora

Probiotic microorganism cultures are able to influence the composition of the natural intestinal flora. In the foreground are lactobacilli and bifidobacteria, which displace potentially harmful germ groups from binding sites of the intestinal epithelium by forming organic acidslactic acid, acetic acid, short-chain fatty acids – and bacteriocins – proteins and low-molecular peptides. In this way, they make it difficult for pathogenic microorganisms to adhere to the intestinal mucosa and hinder their settlement in the intestinal tract. Thus, lactobacilli and bifidobacteria exhibit antibacterial and antimicrobial effects, respectively. Bifidobacteria, in contrast to lactobacilli, can express acetic acid in addition to lactic acid and short-chain fatty acids. These organic acids lower the pH in the intestine. On the one hand, this leads to increased growth of desirable microorganisms and, on the other, to a significant reduction in the number of various pathogenic germ species, such as Fusobacteria, Clostridia, Bacteroides and E. Coli. In addition, bifidobacteria are believed to be able to inhibit the growth of pathogenic bacteria. Among lactobacilli, the species Lactobacillus reuteri in particular has the ability to exert antimicrobial activity on intestinal bacteria and fungi as well as protozoa (single-celled organisms with a cell nucleus). By competing with the aforementioned microorganisms for nutrients and growth factors, the probiotic L. reuteri interfere with the pathogenic bacteria, fungi and protozoa in their development and reproduction. Furthermore, the antimicrobial effect of probiotic cultures is based on the synthesis of hydrogen peroxide. This reacts with thiocyanate, which is produced as a metabolic intermediate in the intestine or comes from food. Subsequently, under the influence of the milk-derived enzyme lactoperoxidase, various oxidation products are formed, which are said to have antimicrobial effects.Finally, with the help of probiotic microorganisms, the balance in the intestine is maintained or restored and a healthy intestinal environment is established.

Immunomodulatory effect

The intestine is the largest immune organ of the human body. The so-called M cells (specialized epithelial cells) of the intestinal mucosa (intestinal mucosa) are part of the immunological barrier and allow constant contact of the intestinal contents with the intestinal associated lymphoid tissue – gut-associated lymphoid tissue, GALT. The GALT plays an essential role in the maintenance of immunological functions. Via M cells, it can recognize potentially pathogenic macromolecules and microorganisms in the intestinal lumen and thus trigger specific immune responses. By rebalancing increased permeability of the intestinal mucosa on the one hand and optimizing the immunological barrier on the other, probiotic microorganism cultures strengthen the barrier function of the intestinal mucosa. The risk of developing autoimmune diseases can thus be limited. With the use of probiotics, immunomodulatory effects can also be achieved outside the intestine. Since probiotic cultures promote the functions of the gut-associated immune system, certain mucous membranes, such as the bronchial mucosa, are influenced in a positive sense via the GALT. Based on experimental findings, the supply of lactic acid bacteria influences the release of cytokines. Cytokines are also called mediators, as they regulate the function of the cells of the immune system. There are four main groups of cytokines:

  • Interferons – with immunostimulatory, especially antiviral and antitumor effects.
  • Interleukins – serve among themselves to communicate the immune defense cells (leukocytes) to fight coordinated pathogens or even tumor cells.
  • Colony-stimulating factors – growth factors of erythrocytes and leukocytes (red and white blood cells), for example, erythropoietin (synonyms: erythropoietin, EPO).
  • Tumor necrosis factors – endogenous messengers of the cells of the immune system; tumor necrosis factor-alpha – TNF-alpha, cachectin – acts on inflammation, hematopoiesis, immune defense, the formation of blood vessels and tumors; tumor necrosis factor-beta -TNF-beta, lymphotoxin – activates macrophages, which subsequently release interleukin-1, interleukin-6 and TNF-alpha.

Finally, probiotics contribute to the improvement of humoral – concentration of immunoglobulins, interferons and interleukins – and cell-mediated – activity of macrophages and B cells – immunological defenses by stimulating cytokine release. The probiotic microorganisms affect, among others, proliferation of tumor cells, multiplication of viruses, activation of macrophages, inflammatory reactions, and antibody formation. The special importance of secretory immunoglobulin A – IgA antibodies was demonstrated in a study. Healthy subjects were given fermented milk containing Bifidobacteria and Lactobacillus acidophilus and an attenuated strain of Salmonella typhi. The result was a more than several-fold higher concentration of specific serum IgA against Salmonella typhi. In another study, Lactobacillus acidophilus was shown to increase both macrophage activity and gamma interferon synthesis in lymphocytes. Macrophages represent scavenger cells of the immune system that take up pathogens by phagocytosis and destroy them intracellularly. The use of probiotics can improve the immune response to oral poliomyelitis vaccination. Poliomyelitis is an infectious disease caused by polioviruses that can affect the muscle-controlling nerve cells of the spinal cord in the unvaccinated and cause permanent paralysis and even death. Probiotic lactobacilli should be administered daily for at least 5 weeks prior to poliomyelitis vaccination to achieve significant effects. They lead to the increase of the following parameters:

  • Activity of virus-neutralizing antibodies
  • Serum concentration of poliospecific IgG.
  • Local immunity of the intestinal mucosa by increasing the concentration of IgA.

Prevention of intestinal and vaginal infections

Fermented dairy products or the lactic acid bacteria they contain are considered important in the prevention or treatment of intestinal infections. This applies to viral, bacterial and fungal infections. In prospective studies, the administration of fermented milk resulted in a lower incidence of gastroenteritis caused by rotaviruses in children. If infection had already occurred, the probiotic germs reduced the frequency of defecation as well as the excretion of the viruses in the stool. Rotaviruses are the most common cause of severe diarrhea. The therapeutic effect of probiotics has also been noted in diarrhea of other etiologies (causes), such as diarrhea caused by radiation and antibiotic therapy. According to a multicenter study, rehydration solutions with an addition of Lactobacillus GG resulted in faster recovery in children with severely watery diarrhea. Furthermore, reports on the positive influence of lactobacilli in diarrhea caused by Clostridium difficile – anaerobic, gram-positive rod bacterium – as a result of antibiotic treatment are known. Also of practical-clinical interest is the protection of probiotic cultures against colonization of the gastric mucosa by Helicobacter pylori, a Gram-negative, microaerophilic bacterium. In a study of 138 patients, it was shown that administration of probiotic yogurt containing lactobacilli and bifidobacteria improved the eradication rate of Helicobacter pylori in combination with antibiotic therapy. Thus, probiotics play an important role in the prevention and treatment of gastritis (inflammation of the gastric mucosa). The use of lactic acid bacteria in the treatment of vaginal fungal infections proved to be quite successful. Under controlled experimental conditions, women with recurrent candidavulvovaginitis consumed yogurt containing Lactobacillus acidophilus daily for a period of 6 months. The antimicrobial effect of Lactobacillus was evident by a significant decrease in clinical symptoms and a reduction in colonization by the fungus Candida albicans. In addition, probiotic germs also protect the rectum and mucous membranes from Candida albicans infestation. By improving the intestinal immune system, normalizing the intestinal flora, and inhibiting inflammatory tissue responses, probiotics can positively influence the disease course of both inflammatory bowel diseases, such as Crohn’s disease and ulcerative colitis, and extraintestinal diseases, such as rheumatoid arthritis and allergies. The cause of inflammatory and allergic reactions is considered to be the misregulation of the immune response to the antigenic structure of intestinal microorganisms. Patients with chronic inflammatory bowel disease or extraintestinal diseases therefore exhibit an incorrect composition of their intestinal flora, as a result of which the tolerance of the intestinal microorganisms is apparently disturbed. Healthy people, on the other hand, tolerate their intestinal flora. In ulcerative colitis patients, treatment with the E. coli strain Nissle led to a significant decrease in disease symptoms within 12 months. In addition to intestinal and vaginal infections, probiotic organisms also play a role in urogenital infections. Several reports suggest that regular probiotic intake reduced the recurrence (reoccurrence) of urinary tract infections.

Effect on irritable bowel syndrome (IBS)

Irritable colon is the irritable bowel syndrome associated with symptoms originating from the small and large intestine. In the majority of cases, certain symptoms are prominent. These include constipation, diarrhea, and flatulence associated with pain. Irritable colon is a factor disease, meaning that the condition can be triggered by several factors. Several lines of evidence suggest that peculiarities in the composition of the intestinal flora are involved in the development of irritable colon. In therapy studies, the effect of probiotics on patients with irritable bowel syndrome was tested, with extremely positive results.The fermented foods, most of which contained Lactobacillus plantarum, restored intestinal balance in the patients and led to the establishment of healthy intestinal flora. This resulted in a significant decrease in both abdominal pain and flatulence. In a study of 77 participants with irritable bowel syndrome, treatment with Bifidobacterium infantis normalized the ratio of anti-inflammatory to pro-inflammatory signaling substances and improved symptoms.

Anticarcinogenic effect

It is considered certain that oral intake of certain strains of Lactobacillus acidophilus and casei is associated with a reduction of bacterially synthesized enzymes via a change in the microbial spectrum in the colon. We are talking about beta-glucoronidase, nitroreductase and azoreductase. These enzymes activate precursors and inactivated forms of carcinogens, respectively, and thus promote the formation of atypical adenomas. The latter represent tumors of mucosal or glandular tissue that have been associated with the development of colorectal cancer. Also, administration of Bifidobacterium bifidum and Lactobacillus GG resulted in a decrease in the concentrations of beta-glucuronidase, nitroreductase, and azoreductase in intestinal contents and feces in human and animal studies. In addition, the probiotic effect of lactic acid bacteria inhibits the activity of 7-alpha-dehydroxylase synthesized by colon bacteria. This enzyme converts primary into secondary bile acids. The latter increase cell proliferation in the colon mucosa, leading to uncontrolled cell growth and thus promoting the development of colon carcinoma. The mechanism of inhibition of 7-alpha-dehydroxylase is based on the acidifying properties of probiotic microorganisms. The expressed lactic and acetic acids and short-chain fatty acids lower the pH in the colon. Since 7-alpha-dehydroxylase is only active at a pH of 7.0-7.5, the now acidic pH leads to a decrease in activity of the enzyme. The formation of carcinogenic secondary bile acids is thus prevented. A reduction in the activities of beta-glucuronidase, nitroreductase, azoreductase and 7-alpha-dehydroxylase in intestinal contents and feces was observed not only with the ingestion of fermented milk, but also after prolonged regular consumption of sauerkraut and kimchi – lactic acid-fermented vegetables, predominantly Chinese cabbage, regularly consumed in Korea. When protein-rich foods are heated, heterocyclic amines are formed that can exert mutagenic or carcinogenic effects. Some strains of lactobacilli are able to bind these amines and render them harmless. Furthermore, lactobacilli can degrade N-nitroso compounds, which are carcinogenic and are formed from nitrites and amines during the frying and smoking of food or in the human stomach. Animal studies confirmed that lactic acid-producing bacteria are able to inhibit tumorigenesis and tumor growth in rats. Rats were administered the probiotically active Bifidobacterium longum and at the same time the carcinogenic 2-amino-3-methylimidazole [4,5-f]-quinoline, which is produced by heating meat and fish. By promoting the degradation of this carcinogenic pyrolysis product, Bifidobacterium longum, the probiotic bacterial strain greatly reduces tumor rates. Animal and clinical studies support that probiotic lactic acid bacteria counteract carcinogenesis in the intestine by the following criteria:

  • Nonspecific stimulation of the immune system
  • Improvement of cellular immunity
  • Reduced formation of carcinogenic substances in the intestine
  • Synthesis of antimutagenic and anticarcinogenic substances by quantitative and qualitative changes in intestinal flora.
  • Inhibition of tumor cell division and tumor growth by glycopeptides and metabolites of lactobacilli.
  • Reduction of the genetic modification effect of the intestinal contents.
  • Reduction of DNA damage already induced.

The risk of extratestinal carcinogenesis is also significantly reduced by regular use of probiotic lactobacilli. The results of numerous studies made it clear that in healthy subjects who consumed roasted beef and also fermented milk with Lactobacillus casei, urinary mutagenicity decreased.In addition, probiotic intake reduced the recurrence rate (reoccurrence) of superficial bladder cancer.

Lowering serum cholesterol levels

The cholesterol-lowering effect of probiotic lactic acid bacteria is based on the observation that men from the Masai tribe in Africa drink 4-5 liters of fermented milk daily and have exceedingly low serum cholesterol levels. In particular, fermented milk and milk enriched with Lactobacillus acidophilus led to a decrease in serum cholesterol in some studies. However, studies also exist that failed to demonstrate a relationship between probiotics and serum cholesterol levels. For example, a number of targeted studies with yogurt, predominantly prepared using Lactobacillus acidophilus, yielded inconsistent results. A possible mechanism of action under discussion is an inhibitory effect of probiotics on the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase – HMG-CoA reductase. In the liver, HMG-CoA reductase converts HMG-CoA, which is formed by the breakdown of free fatty acids, to cholesterol. Due to the enzyme inhibition, endogenous cholesterol synthesis is ultimately restricted and serum cholesterol levels are lowered. Furthermore, it is believed that probiotic lactic acid bacteria can deconjugate conjugated bile acids, resulting in less bile acids being reabsorbed. The result is an increased de novo synthesis of bile acids. Endogenous cholesterol is increasingly used for their regeneration, resulting in a reduction of serum cholesterol levels. In addition to the effect of probiotics on endogenous cholesterol, the influence on exogenous cholesterol is probably also decisive for the cholesterol-lowering effect. It is assumed that probiotic cultures can directly degrade dietary cholesterol.

Effect in lactose intolerance (milk sugar intolerance)

Individuals with lactose intolerance are unable, or only partially able, to break down lactose (milk sugar) ingested with food. Poor lactose digestion is due to a lack of or reduced production of the enzyme beta-galactosidase, also known as lactase. In the small intestine, lactase breaks down milk sugar into the sugars glucose and galactose, which are usable by humans. If uncleaved lactose reaches the large intestine, it is fermented by intestinal bacteria. The fermentation products lead to flatulence (bloating), meteorism (flat stomach) with muscle tension and pain in the abdominal area, a feeling of pressure and diarrhea (diarrhea) after consuming milk or dairy products. Consumption of dairy products in fermented form is comparatively well tolerated by lactase deficiency syndrome patients. The reason for this is the high number of live lactic acid bacteria that contain the lactose-cleaving enzyme beta-galactosidase. This is firmly enclosed in the bacterial cell and, supported by the buffering capacity of milk, can pass through the stomach unharmed – it is rapidly inactivated at a pH of less than 3. Due to the high bile salt concentration in the upper small intestine, the permeability of the bacterial cell membrane is presumably increased, promoting the release of lactase into the intestinal lumen. As a result, increased lactose degradation occurs. Crucial for the release of beta-galactosidase from bacterial cells is the structure of the cell wall, which differs from bacterium to bacterium. When comparing Lactobacillus acidophilus and Lactobacillus bulgaricus with the same lactase activity inside the cell, it was found that the intake of probiotic dairy products containing mainly L. bulgaricus resulted in significantly higher lactose tolerance in patients. This is due to the specific wall structure of this bacterial species, which allows increased lactase secretion and thus increased lactose cleavage in the intestinal lumen. Since different bacterial strains and species are used in the production of fermented milk products, lactose tolerance varies depending on the product consumed. Heat-treated fermented milk products have a less pronounced effect on lactose intolerance. Therefore, patients should be careful to select only those dairy products with live germs.

Delaying the aging process

Scientific findings increasingly demonstrate the importance of intestinal microorganisms for functions of the human organism. Of particular interest is the influence of intestinal flora on the aging process. With increasing age, the number of bifidobacteria decreases and that of Clostridium perfringens decreases. This leads to increased putrescence – bacterial protein degradation – in the colon and thus to the formation of toxic degradation products. It is possible that these toxic degradation products are involved in the aging process. As early as the end of the 19th century, the Russian bacteriologist Ilya Metschnikov saw a link between probiotic microorganisms and aging. Since probiotics are able to modify the intestinal flora in favor of bifidobacteria, putrescence in the colon is reduced. Thus, regular intake of probiotic lactic acid bacteria could delay the aging process.

Diverticulosis, diverticulitis

Diverticulosis is a change in the colon in the form of small outpouchings (diverticula) of the entire intestinal wall and is usually completely asymptomatic. Diverticulitis, on the other hand, is a disease of the colon in which inflammation forms in the diverticula of the intestinal mucosa. Various bacterial strains have been shown to be effective in both prevention and therapy of diverticulosis and diverticulitis. Therefore, this type of therapy will play a greater role in the future than it has in the past.

Radiatio (radiation therapy)

It was found that patients after pelvic radiotherapy suffered less diarrhea (diarrhea) when they ingested lactic acid-producing bacteria. In addition, consumption of fermented dairy products reduced the extent of late effects of radiation.

Atopic eczema (neurodermatitis)

The administration of probiotic bacteria was able to reduce the incidence of atopic eczema by half in newborns. In this study, both the mothers before birth and the newborns received the probiotic bacterial strain Lactobacillus GG until six months after birth. Subsequent follow-up -(follow up) of the study participants showed persistence of this protective effect.

Potential effect in hepatic encephalopathy and renal insufficiency

Patients with hepatic encephalopathy (brain dysfunction resulting from insufficient detoxification function of the liver) and renal insufficiency (kidney weakness) suffer from liver and kidney dysfunction, respectively. By reducing toxic protein degradation products and decreasing the absorption of ammonia (NH3) due to a decrease in intestinal pH, probiotics can contribute to the prevention of these diseases or alleviate the symptoms of an existing disease. For additional functions of probiotics, see the “Prevention” and “Therapy” subtopics below.