Marmara University, Faculty of Pharmacy
"A healthy gut is the foundation of a healthy life."
What is microbiota?
Did you know that there are at least 1014 (about 100 trillion) microorganisms in our body? The vast majority of these microorganisms live in the human gastrointestinal (GI) tract, that is, the intestines. Our intestines host various bacteria, yeasts, viruses and parasites. All of these microorganisms constitute the intestinal flora. The communities created by microorganisms are called microbiota, and the genome carried by microorganisms is called microbiome.
In healthy individuals, the intestinal flora contains 6 types of bacterial microbiota, namely Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Fusobacteria and Verrucomicrobia. The most common among these types are: Lactobacillus, Bacillus, Enterococcus, Ruminococcus and Clostridium.
At birth, the human gut is nearly sterile and colonized by our mother's microbiome. The mode of delivery (vaginal or cesarean section) plays an important role in shaping the newborn's microbiome.
Intestinal microbiota takes part in important events such as protection of the intestinal barrier, shaping and maturation of the immune system, regulation of human metabolism and absorption of nutrients and drugs. Additionally, it has a dynamic structure as it is affected by various factors such as age, genetics, environment, lifestyle and basically nutrition.
Intestinal dysbiosis
The bacteria in the intestinal microbiota contain a certain ratio of beneficial and harmful bacteria. When the rate of harmful bacteria in our intestines increases, a pathological process we call "microbial dysbiosis" begins.
Our diet is the most important environmental factor that determines the content of intestinal microbiota. Change in diet, especially inadequate and unbalanced nutrition, leads to changes in the number and content of microorganisms in the microbiota, that is, dysbiosis. The microbial dysbiosis process is associated with many diseases such as allergy, inflammatory bowel disease, cancer, lupus, asthma, multiple sclerosis, Parkinson's disease, celiac disease, obesity, diabetes and cardiovascular diseases.
Another situation in which the ratio of beneficial/harmful bacteria is disrupted is the use of antibiotics. It is known that the antibiotics used disrupt the composition and enzyme activity of the gut microbiota. After antibiotic treatment, our gut microbiota is reshaped. During this process, foreign bacteria or resistant species may settle in the intestinal flora. All of these are situations that can cause permanent changes in the microbiota and diseases.
Today, probiotic, prebiotic and synbiotic (combination of probiotics and prebiotics) components are used to strengthen the beneficial microflora of the intestine.
What is probiotic?
The term probiotic is a word of Greek origin and means 'for life'. Probiotics are live microorganisms that increase beneficial bacteria in the intestine, reduce pathogenic bacteria, and maintain and renew the natural balance of bacteria. In addition to maintaining bacterial balance, these microorganisms also prevent the negative effects of stress and antibiotic use. The most important known probiotics are Lactobacillus, Bifidobacterium, Streptococcus and Saccharomyces.
Probiotics are mostly classified as bacterial, lactic acid and non-lactic acid bacterial species and yeasts. Especially lactic acid-producing bacterial cultures benefit health when consumed in sufficient quantities. Most strains of probiotics added to food products are preferably isolated from naturally fermented products. Cultures of lactic acid bacteria such as Enterococcus, Lactobacillus, and Bifidobacterium have been confirmed to be beneficial bacterial species for humans.
Benefits of probiotics
Probiotics, when taken in adequate amounts, provide many beneficial effects on our body. Research has shown that probiotics are effective in the prevention and treatment of type 2 diabetes. Some types of probiotics increase insulin sensitivity and improve the lipid profile in obesity, type 2 diabetes and dyslipidemic diseases. In addition, taking probiotics in appropriate amounts reduces metabolic syndrome, the risk of overweight and obesity, and peripheral inflammation.
It has been reported that the use of probiotics is effective in many different diseases such as lactose intolerance, diarrhea, inflammatory bowel diseases, obesity, diabetes, allergies and cancer.
Lactose intolerance
Lactose intolerance is a disorder caused by the decrease in the lactase enzyme as a result of the deterioration of the intestinal mucosa due to reasons such as advancing age, digestive system diseases or antibiotic use. Studies have shown that when components containing Bifidobacteria and other probiotic bacteria are given to lactose intolerant patients for a long time, the symptoms decrease or disappear completely.
Diarrhea
Probiotics increase IgA secretion and local interferon release in the intestine by stimulating the immune system. In this way, it plays a healing role in diarrhea by affecting the intestinal mucosa. Probiotics such as Saccharomyces boulardii show beneficial effects by changing the microflora of the intestines against pathogenic bacteria. Probiotics are of great importance in diarrhea that develops due to antibiotic use, especially in children.
Inflammatory bowel diseases
Probiotics affect the disease by modifying the immune response in our body. Studies have shown that probiotics are effective in both adjuvant (preventive) and maintenance treatment of inflammatory bowel diseases.
Immune system and probiotics
One of the most important known benefits of probiotics is their effects on our immune system.
To maintain intestinal balance, a healthy interaction between the host immune system and microbiota is required. Disruption of this interaction can cause dysbiosis due to changes in bacterial function and diversity. Developing dysbiosis can lead to the occurrence of infectious diseases and the development of autoimmune diseases. This puts the immune system's health at risk.
Probiotics stimulate immune system compounds that are secreted or present in the cellular barrier. In this way, they improve the body's defenses by triggering the immune response and maintaining a balance between pro- and anti-inflammatory cytokines secreted by activated immune cells.
Research shows that probiotics affect systemic immune responses and ensure homeostasis of healthy microbiota in the intestinal mucosa. Therefore, it is thought that probiotics can be used as a preventive treatment in the treatment of immune-mediated diseases. There is evidence that probiotics promote the production of some cytokines, including IL-10, transforming growth factor (TGF)-β, IL-12, and INF-γ, which regulate the immune response and reduce allergic inflammation.
The immune-supporting mechanisms of probiotics include mucus secretion, antimicrobial peptide production, maintenance of gastrointestinal-epithelial barrier function, ensuring adequate interaction between the intestinal microbiota and mucosal immune cells, and finally assisting in the activation of the host immune system.
In these respects, probiotics act as a non-specific adjuvant (preservative) to the innate immune response.
Allergy and probiotics
Probiotics are also very effective in treating and preventing allergic diseases. Many allergic reactions (e.g. eczema, asthma, atopic dermatitis) may develop due to intestinal dysbiosis. For example, there is an association between the presence of Clostridium difficile colonization in the intestines and allergies in children. Research shows that the gut microbiota of children with atopic dermatitis has less diversity and lower levels of Bifidobacterium than healthy children. Higher numbers of Staphylococcus aureus and Enterobacteriaceae and lower numbers of Bifidobacterium were detected in allergic children compared to healthy children.
Allergies such as eczema are thought to develop in association with a decrease in the density of Bifidobacterium, Akkermansia, Faecalibacterium and Lachnospira in the gut microbiota, especially in early life.
The therapeutic potential of probiotics in allergic diseases is achieved through various mechanisms such as regulating the immune system, inhibiting harmful bacteria in the intestine, reducing the effects of pathogens and strengthening the function of the intestinal wall. Studies have reported that various probiotic supplements can balance the gut microbiota, regulate the immune system and reduce allergies. Synbiotics, a synergistic combination of probiotics and prebiotics, have proven beneficial for different allergic conditions, for example by reducing asthma-like symptoms and the use of asthma medications.
Cancer and probiotics
Probiotics show anticancer and antimutagenic activity in our body through different mechanisms. Binding, cleavage and inhibition of mutagen; inhibition of procarcinogen and conversion of harmful, toxic and highly reactive carcinogens; lowering of intestinal pH by short-chain fatty acids (SCFAs) formed during the breakdown of indigestible carbohydrate are some of these mechanisms.
Studies have reported that probiotic bacteria and yeasts eliminate the toxicity of carcinogens and the induction of cancer cell death. In particular, probiotic lactic acid bacteria are considered one of the most important microorganisms in anti-carcinogenic activity. Their effects depend on metabolic properties, strain-specific molecules presented, and secreted components. Different Lactobacillus species and their components have been reported to have anti-proliferative properties that fight cancer cells in vitro and in vivo.
A study in 46 rheumatoid arthritis patients investigated the role of taking Lactobacillus casei for 8 weeks. As a result of the study, treated patients showed improvement in disease activity score, increase in serum IL-10 levels, and decrease in tumor necrosis factor, IL-6 and IL-12 levels.
However, it should not be forgotten that cancer immunotherapy offers a very effective treatment for cancer types that are resistant to chemotherapy and radiotherapy. Studies are showing that probiotics reduce the effectiveness of immunotherapy. Therefore, cancer patients should not use probiotics without consulting their doctor.
Obesity and probiotics
The microbiota of individuals with obesity is different from that of healthy individuals. Studies have shown that the rate of Firmicutes increases and the rate of Bacteroidetes decreases in the microbiota of obese individuals. This indicates that the balance of beneficial and harmful bacteria in the microbiota is disturbed. In addition, the increase in fat tissue in the body due to obesity increases inflammation and therefore becomes the source of various diseases.
At this point, regulation of the diet and balance of external nutrients are of vital importance. Excess fat and sugar in the diet causes pathogenic microorganisms to grow and multiply. Especially excess fatty acids taken from outside contribute to the proliferation of some lactobacilli (Streptococci, Lactococci, Clostridia). A diet high in fat and sugar leads to a decrease in the mucus layer in the intestines and the growth of Helicobacter Pylori and Entomoeba histolytica species. The dysbiosis that develops as a result causes inflammation of the fat tissue, increasing the risk of developing obesity and diabetes.
A known effect of probiotics is to reduce the risk of obesity. Probiotics reduce the accumulation of fat cells in our body and in this way regulate metabolic and inflammatory processes. It also corrects intestinal dysbiosis and prevents inflammation of fatty tissue.
What are natural probiotics?
Probiotics, especially lactic acid bacteria including Lactobacillus, Bifidobacteria and Streptococcus species, can be taken as supplements or naturally through fermented foods. Fermented foods have distinctive functional properties such as enzyme production, antimicrobial, peptide and antioxidants, and other probiotic properties. Examples of foods with high probiotic content include yoghurt, pickles, soy products, some cheeses, kefir, and sourdough bread. Adding these foods to the diet in a balanced manner will regulate the intestinal microbiota and eliminate the risks of diseases that may develop due to dysbiosis.
What is the recommended probiotic dosage?
For healthy adults, the dosage specified by ISAPP (International Scientific Association for Probiotics and Prebiotics) is 1 x 10⁸ to 1.8 x 10¹² CFU twice daily, depending on the strain and disease, and the duration of treatment varies from 3 weeks to 5 months.
For elderly patients, dosage to improve immune response ranges from 1 x 10⁷ to 3 x 10¹¹ CFU for 3-12 weeks. The clinical effectiveness of probiotics for children has been found to be between 1-5 billion CFU and is especially effective on antibiotic-induced diarrhea.
Misconceptions
Will there be more benefits as the probiotic dose is increased?
Just because a probiotic product has a higher number of colony forming units (CFU) does not mean it will have more effect. The best dose is the dose that has been tested in humans and shown to provide positive results. These levels can range from 100 million to one trillion CFU per day. It is important to comply with the recommended dosage schedules during the treatment process in order to obtain maximum therapeutic benefit.
Does increasing the variety of strains in the probiotic product also increase the therapeutic benefit?
There are different studies conducted on the strain diversity of probiotic products. While some studies support the benefits of a single-strain probiotic product, other studies show that specific mixtures of probiotic strains have positive results. However, it should not be thought that a variety of strain will always produce more beneficial effect.
Does the specificity of the strain of choice matter?
Studies show that not all probiotics show the same effectiveness. Depending on the intended use of probiotics, different probiotic strains or their mixtures can be preferred. When making your choice, you can seek advice from a doctor/pharmacist or get support from internationally valid probiotic guides.
Does the sugar content of probiotic foods reduce the effectiveness of treatment?
Some of the frequently preferred probiotic foods today may contain added sugar. Probiotic fruit-flavored yoghurts and kefirs can be given as examples. Most of the research examining the health benefits of probiotics in foods has been conducted on sugary yoghurts/drinks. Therefore, sugar does not adversely affect the effects of probiotics. Taking sugar with probiotic foods does not reduce the effectiveness of the treatment if it is part of a balanced nutrition process.
Do all fermented foods display probiotic properties?
While fermented foods are prepared, they go through stages such as pasteurization, baking, smoking or filtering. These steps can eliminate live cultures in the fermented food, leaving it unable to provide viable microbes. However, even if a fermented food provides a live source of microbes, its health benefits may not be tested.
Foods defined as probiotic foods contain live microbes that have been shown to have an effect on health when given in adequate amounts. If a fermented food contains a studied probiotic in a beneficial dose, then it can be said to have probiotic properties.
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