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1 FGAOU VO First Moscow State Medical University named after M.V. THEM. Sechenov Moscow State Medical University (Sechenov University), Moscow
2 GBUZ "DGKB No. 9 named. G.N. Speransky DZM ", Moscow; FSBI NMITs DGOI im. Dmitry Rogachev "Ministry of Health of Russia, Moscow
For citation: Moonblit D.B., Korsunsky I.A. Pro- and prebiotics in the prevention and treatment of allergic diseases // BC. 2016. No. 6. S. 354-357
The article discusses aspects of the use of pro- and prebiotics in the prevention and treatment of allergic diseases
For citation. Moonblit D.B., Korsunsky I.A. Pro- and prebiotics in the prevention and treatment of allergic diseases // BC. 2016. No 6.P. 354–357.
Introduction
From the second half of the XX century. there has been a marked increase in the prevalence of allergic diseases such as atopic dermatitis, allergic rhinitis and asthma. According to the latest data from the International Study of Asthma and Allergies in Childhood, which contains data on more than a million children from 98 countries, a high prevalence of allergic diseases is noted in both developed countries and economically backward ones.
These allergic diseases are already among the most pressing public health problems around the world. Thus, in the United States, bronchial asthma annually causes 10.1 million days of absence from school, 200 thousand hospitalizations, 1.9 million days of inpatient treatment. Allergic rhinitis has a significant impact on the quality of life of patients, leading to costs of drugs and doctor visits in the amount of $ 3.4 billion per year. Atopic dermatitis also reduces the household budget. For example, in Canada, the associated total cost is about CAD 1.4 billion per year.
In 1989, Strachan put forward the so-called "hygiene hypothesis", suggesting that a pronounced increase in the prevalence of allergic diseases may be associated with a decrease in the microbial antigenic load on the child's body, which, in turn, affects the immune response. This theory was supported by animal studies: scientists identified differences between populations of Th1 and Th2 lymphocytes and proved that infections lead to a Th1 response and the release of the corresponding cytokines, in turn suppressing the Th2 response associated with IgE-mediated allergic reactions.
However, not all subsequent immunological and epidemiological studies have confirmed the theory of "excess hygiene". Later, there were suggestions about the relationship between the intestinal microbiocenosis and the immune system through the interaction of dendritic and T-regulatory cells, bacterial metabolites and cytokines, which may help to understand the mechanism of allergies. As a result of the experiments, a new direction in research has emerged, devoted to the modification of bacterial colonization of the intestine with the help of pro- and prebiotics.
What are pro, pre- and synbiotics?
The history of probiotics began more than a hundred years ago, when Ilya Mechnikov, who worked at Pasteur's laboratory in Paris, hypothesized that lactic acid bacteria could improve human health and prolong life. His diet of milk, fermented by a bacterium, which he called "Bulgarian bacillus", became widely known in Europe. Probiotics got their name in 1965, when Lilly and Stillwell identified microbial factors that can stimulate the growth of other microorganisms, as opposed to the effect of antibiotics.
Probiotics are living microorganisms that can be included in various types of food (including drugs and food additives), as well as have shown benefits to human health in controlled studies.
Probiotic strains are classified according to characteristics such as class, species, and alphanumeric name. More often than others, the following probiotic strains were used in studies aimed at preventing the development of allergic diseases: lactobacilli: L. rhamnosus (mainly HN001 and GG), L. acidophilus, L. reuteri, L. lactis; bifidobacteria: B. animalis, B. longum, B. bifidum, B. lactis.
Strain specificity is extremely important because the results of clinical studies, as well as meta-analyzes and review articles on specific strains, cannot be used as evidence of the effectiveness of strains for which research has not yet been conducted. Also, if the effectiveness of a particular strain has been confirmed at a certain dose, it cannot be said that with a decrease in the dose, its effectiveness will remain.
Let's try to apply this postulate to clinical practice. If, for example, the L. acidophilus and B. infantis strains are included in the composition of the drug that we give the patient, and we want to achieve the effect that was shown in the study in which the L. rhamnosus strain was used, then this approach is fundamentally wrong. It is also necessary to compare the dose of the probiotic, which showed a beneficial effect, with the dose contained in the drug we are prescribing to the patient.
Prebiotics- these are food substances that are poorly digested and thus have a positive physiological effect on the host, selectively stimulating the necessary growth or activity of the intestinal microflora.
Many prebiotics are used as food additives in chocolate, cookies, cakes, dairy products and cereals. Of the most famous prebiotics, it is necessary to note oligofructose, inulin, galacto-oligosaccharides, lactulose, as well as breast milk oligosaccharides.
Finally, it is necessary to mention synbiotics, which have been used in clinical trials in recent years. They are a combination of pro- and prebiotics, suggesting to combine the beneficial effects of both.
The concept of using pro- and prebiotics in the prevention and treatment of allergic diseases
When scientists and clinicians pondered which strategy was the most effective and cost-effective in tackling the growing problem of allergic diseases, they concluded that it was necessary to focus on primary prevention. Since allergic diseases often manifest themselves already during the first year of a person's life, prevention strategies should be focused on pregnancy and the early postnatal period.
Since before the first symptoms appear, it is impossible to reliably say which of the children will suffer from allergic diseases, prevention is aimed primarily at children from the so-called risk group. This group, firstly, includes children with a family history of allergic diseases.
It is known that the ecosystem of the human intestine is extremely complex, contains more than 1014 microorganisms (which is 10 times the number of cells of the organism itself) and contains a huge potential for local and systemic influence. These effects are especially important in infancy, when the sterile intestines of the newborn are rapidly colonized by bacterial flora.
For the first time, probiotics were used to prevent the development of allergic diseases by scientists from Finland; Isolauri et al. gave probiotics to women during pregnancy and in the early postnatal period. The authors noted a 50% reduction in the risk of developing atopic dermatitis, which generated a lot of enthusiasm among scientists and spawned a whole series of studies that used different strains of probiotics in different populations.
Despite the fact that the results of many subsequent studies have been extremely controversial, the concept of using probiotics for the prevention and possibly treatment of allergic diseases remains extremely attractive.
It is possible that the observed discrepancy in research results can partly be explained by epigenetic differences between populations and specific responses to specific probiotic strains within a specific population. Today we are far from fully understanding the details of the functioning of the complex intestinal ecosystem.
The studies carried out focused mainly on two aspects: prevention of the development of allergic diseases with the help of pro- and prebiotics and their use in the treatment of allergic diseases.
Probiotics in the prevention of the development of allergic diseases
As mentioned above, the use of probiotics as a preventive measure against the development of allergic diseases has been in the focus of attention of scientists for a long time. This allowed us to accumulate a sufficient amount of data in order to conduct a qualitative analysis. In 2015, Zuccotti et al. published a meta-analysis summarizing the data of 4,755 children (2,381 in the probiotic group and 2,374 in the control group). The studies differed in their design: probiotics were given to both women during pregnancy (and sometimes lactation) and their children for a certain period of time (from 6 months to 2 years). The probiotic strains used in the studies included in the meta-analysis also often differed: four studies used probiotic combinations containing lacto- and bifidobacteria; in three studies, single strains of lacto- and bifidobacteria were used separately; the other ten used different strains of lactobacilli. These differences highlight the heterogeneity of the data analyzed.
Despite the differences in study design and the difference in the strains of probiotics used, the authors made a confident conclusion that the use of probiotics during pregnancy and / or during the first months of life in children led to a statistically significant reduction in the risk of developing atopic dermatitis RR 0.78. A particularly pronounced effect was noted in those cases when a combination of several strains of probiotics RR 0.54 was used.
It can be assumed that the preventive effect is not as long-term as we would like, since there was no statistically significant difference in the risk of developing bronchial asthma RR 0.99, bronchial obstruction RR 1.02, or allergic rhinoconjunctivitis RR 0.91.
As can be seen from the results of this meta-analysis, probiotics are a means of preventing the development of atopic dermatitis and can potentially be indicated for use during pregnancy and lactation.
Probiotics in the treatment of allergic diseases
Most of the existing studies have been conducted with infants or young children. This is probably due to the fact that, as soon as the formation of intestinal microbiocenosis and allergic phenotype is completed, the therapeutic potential of using probiotics is sharply reduced.
The therapeutic effect of probiotics has been well studied in children with atopic dermatitis. The results of a Cochrane systematic review by Boyle et al., Which summarized data from 12 studies, showed no significant effect of probiotics in the treatment of atopic dermatitis. The results showed that probiotic therapy did not reduce the incidence of symptoms such as itching or sleep disturbance, nor did it affect the severity of the disease. Thus, it is extremely unlikely that the use of probiotics could play a significant role in the treatment of atopic dermatitis. The authors noted the heterogeneity as well as the low quality of some studies.
Since asthma and allergic rhinitis mainly appear at an older age (when the intestinal flora and the characteristics of the immune response have already been formed), it can be assumed that the potential effect of probiotics on the course of these diseases will be more limited. Perhaps for this reason, there is very little qualitative research on this topic. Vilagoftis et al. conducted a meta-analysis of existing randomized trials and showed that the use of probiotics for allergic rhinitis was associated with a decrease in symptoms and a reduction in the frequency of drug use. However, it should be noted that the lack of standardization of studies, the heterogeneity of design and study populations complicated the interpretation of the data. The authors concluded that although the data indicate a positive effect of probiotics on the course of allergic rhinitis, they are not enough for final conclusions. The results of studies of the effect of probiotics on the course of asthma, considered in the meta-analysis, showed that to date there is no data confirming the positive effect of their use.
Prebiotics and allergic diseases
The use of prebiotics, such as fermentable oligosaccharides, seems to be a very interesting approach, since they can promote colonization of the intestine with beneficial microflora, especially bifidobacteria, which, in turn, can lead to a more pronounced effect than the addition of individual probiotic strains.
To date, not very many studies have been conducted in which prebiotics have been used to prevent the development of allergic diseases. However, the available data allow us to draw a number of preliminary conclusions.
Much of the research has focused on the postnatal period, when prebiotics are added to formula milk or food. In general, the results can be considered quite optimistic: the risk of developing atopic dermatitis decreased with the use of prebiotics both in children at risk for the development of allergic diseases and in children of the general population.
Research on the use of prebiotics during pregnancy suggests that they can protect the baby from developing allergies. This may be due to both the effect on the mother's microbiocenosis and on the metabolism of short-chain fatty acids during fetal development, and the effect on the composition of breast milk.
The place of prebiotics in the treatment of allergic diseases in children remains unclear. Very limited information on this topic, as well as conflicting research results, do not give grounds to recommend them as a therapeutic agent.
Recommendations for the use of pro- and prebiotics in clinical practice
The results of the above-mentioned meta-analyzes were reflected in a number of consensus documents of various international organizations and associations on the use of probiotics in the prevention and treatment of allergic diseases in children. These documents, as well as quality meta-analyzes, provide clinicians with answers to a number of important practical questions.
Should Probiotics Be Used During Pregnancy?
The European Academy of Allergy and Clinical Immunology (EAACI) consensus document on food allergy and anaphylaxis states that “there is not sufficient evidence to recommend that women change their diet during pregnancy or take any supplements (eg probiotics) to preventing the development of food allergies in their children. " The consensus documents of a number of other leading associations and organizations do not make any recommendations regarding the use of probiotics during pregnancy. The only organization recommending the use of probiotics during pregnancy is the World Allergy Organization (WAO): a 2015 document recommends the use of probiotics in pregnant women whose children are at risk of developing allergic diseases, as it can have a positive effect. expressed in the prevention of the development of atopic dermatitis. The authors note that this recommendation is selective and based on very low quality evidence.
Should I use probiotics while breastfeeding?
A similar picture is observed regarding the use of probiotics during lactation: the EAACI advisory document says that there is not enough evidence to recommend lactating women to change their diet or use any supplements (for example, probiotics) in order to prevent the development of food allergies in children. Despite the poor quality of the existing evidence base, WAO suggests using probiotics in breastfeeding women whose children are at risk of developing allergic diseases, as this may reduce the risk of developing atopic dermatitis. A number of other conciliatory documents do not provide any recommendations on this issue.
Should probiotics be used in newborns to prevent the development of allergic diseases?
There is complete unanimity among the experts on this issue. The consensus document of the World Gastroenterological Organization says that to date the best quality evidence exists regarding the reduction of the risk of developing atopic dermatitis when using certain strains of probiotics in pregnant mothers and newborns up to the age of 6 months. ... The WAO recommendations express a similar position, although the authors note the low quality of the evidence due to the high heterogeneity of studies.
Should probiotics be used in the treatment of allergic diseases?
The question of the need to use probiotics in clinical practice in children who already suffer from allergic diseases is extremely important. To date, there is not enough evidence to recommend the use of probiotics for the treatment of allergic diseases. The authors of meta-analyzes agree that probiotics do not reduce symptoms of atopic dermatitis or asthma. It is possible that in the future, specific strains of probiotics can be used in certain groups of patients with atopic dermatitis or asthma, but so far their use in clinical practice is not advisable.
Should I use prebiotics during pregnancy and lactation?
To date, we are not aware of any recommendations provided by leading international organizations or meta-analyzes on this topic. This is due to the relatively small number of studies and, accordingly, insufficient evidence base, which does not allow making unambiguous conclusions. It is possible that prebiotics will take their place in preventing the development of allergic diseases in children, but this remains to be seen. While there is no proven prophylactic potential for prebiotics, adequate fiber (whole grain breads and cereals, legumes, fruits and vegetables) should be welcomed in a normal, healthy diet.
Conclusion
The increase in the incidence of allergic diseases worldwide is an important signal that the modern environment is negatively affecting the child's immune system. This process represents a long-term impact on the health of the child, which in part carries over into adulthood. Understanding what interventional methods can be used during pregnancy and during the first months of a child's life may reduce the risk of developing a number of chronic diseases, including allergic pathology.
Despite the fact that probiotics are a very interesting option for preventing the development of allergic diseases and their treatment, you need to be very careful in their use. As a preventive measure, probiotics can be used in pregnant and lactating women whose children are at risk of developing allergic diseases in order to reduce the risk of developing atopic dermatitis. Prebiotics can probably play a role in the prevention of allergic diseases, but a large evidence base is required for their introduction into routine clinical practice. According to existing data, both probiotics and prebiotics are not indicated for the treatment of allergic diseases.
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