Despite the improvement of preventive and therapeutic methods and the emergence in the arsenal of doctors of new highly effective drugs, infections of the respiratory tract (GI) and of the gastrointestinal tract (mainly acute diarrhea) continue to be a urgent problem, especially in children attending groups of children. Thus, in children attending kindergartens, the risk of developing respiratory and gastrointestinal tract infections is 1.5 to 3.0 times higher than that of “domestic” children [1, 2].
One of the most discussed approaches in recent years for the prevention and treatment of IDPs and the treatment of acute diarrhea is the use of probiotics. It is believed that the use of probiotics can improve the immune properties of the macro-organism, especially resistance to infectious diseases of the respiratory and gastrointestinal tract. It should be noted that a specific prophylactic or therapeutic effect can only be attributed to a specific probiotic strain, the proof of effectiveness of which has been obtained in adequate controlled clinical trials, and this effect should not be transferred to other strains of the same type [3].
Currently, the most studied probiotic strains of microorganisms with established positive effects on human health are Lactobacillus rhamnosus GG (ATCC 53103) and Bifidobacterium lactis Bb-12 ( species Bifidobacterium animalis, ATCC 25527) [4].
In 2010, a new medicine for children from 3 years old containing L. was registered in USA. rhamnosus GG and B. lactis Bb-12 - "Beefiform Kids" (State registration certificate n ° LSR-009020/10 of 08/31/2010, Ferrosan A / S, Denmark). In addition to the probiotic strains, Bifiform Kids also contains vitamins B1 and B6. Vitamin B1 (thiamine) - one of the most important vitamins of energy metabolism, which is a necessary component of carbohydrate metabolism, also plays an important role in the metabolism of proteins and fats and has an effect on the conduct of l nervous excitement in cholinergic synapses. Vitamin B6 (pyridoxine) is involved in the synthesis of nucleic acids, regulates calcium-phosphorus metabolism, improves liver function, participates in hematopoiesis and is important for the normal functioning of the central and peripheral nervous system.
The drug Bifiform Kids is indicated in children over 3 years of age for the treatment of acute intestinal infections of established and unknown etiology, including viral diarrhea; for the prevention and treatment of dysbiosis of various etiologies; in the treatment of food allergies.
Efficacy of the use of B. lactis Bb-12 and L. rhamnosus GG in various nosological forms in pediatric practice has been demonstrated in a number of clinical studies.
Probiotics colonize the intestinal wall and limit the excessive growth of pathogenic bacteria, and competition for mucosal receptors reduces the adhesion and growth of enterotoxic gram-negative anaerobes and enteropathogenic viruses. Lactobacilli and bifidobacteria secrete substances with antibacterial properties, reduce the acidity of the intestinal contents, allowing “beneficial” bacteria to multiply on the surface of the mucosa [5]. In addition, L. rhamnosus GG, has an immunomodulatory effect, can reduce the severity of inflammation of the intestinal wall [5].
The European Society of Pediatric Gastroenterology, Hepatology and Nutrition has conducted the largest study on the use of L. rhamnosus GG in the treatment of moderate to severe acute diarrhea in children [ 6]. The study involved 287 children aged 1 to 36 months from 10 countries. Patients who received standard treatment - rehydration therapy - were randomized to receive L. rhamnosus GG or placebo. With the use of lactobacilli, the duration of diarrhea decreased on average by 14 hours, and in children with a 20-hour etiology of rotavirus, the length of hospital stay and the likelihood of prolonged persistence of diarrhea has been reduced [6].
In 2002, a meta-analysis of RCTs was published that examined the use of standard rehydration therapy in combination with probiotics in the treatment of acute diarrhea in children. The following probiotics were used in the studies: L. rhamnosus GG - 9 studies, other probiotics (bifidobacteria, other lactobacilli, thermophilic streptococci, yeast fungi) - 9 studies. In most cases, a decrease in the duration of the disease by 0.6-1.0 days was detected, while in 3 studies, a decrease in the duration of the diarrhea by 1.5-3.0 days has been observed. When using lactobacilli, the greatest reduction in the duration of diarrhea was observed - by 1.1 days [7]. In another meta-analysis, a significant decrease in the number of stools by 1.6 / day on day 2 of lactobacillus treatment was compared with the control and a decrease in the duration of diarrhea in children by 0.7 day on average [8].
Thus, the use of the probiotic L. rhamnosus GG is an appropriate complement to rehydration therapy in the treatment of acute infectious diarrhea in children.
In addition to the therapeutic effect in acute diarrhea, the use of L. rhamnosus GG is effective for the prevention of antibiotic-associated diarrhea (AAD), which is a common side effect of antibiotic therapy.
The mechanism of action of lactobacilli in the treatment and prevention of ADA is to stimulate local immunity of the intestinal mucosa (synthesis of IgA and IgG, release of interferon); the production of compounds with antimicrobial activity and an obstacle to the adhesion of enteropathogens to intestinal epithelial cells [9].
In one study, 167 children aged 2 weeks to 13 years (4.5 years on average) who received antibiotics for respiratory infections were randomized to L. rhamnosus GG or placebo for 2 weeks from the start of antibiotic therapy. It was found that in the group of lactobacilli, the incidence of symptoms of diarrhea decreased by around 70% compared to placebo (5% vs 16%, respectively) [10].
In another study of 202 children aged 6 months to 10 years who received oral antibiotics, the use of L. rhamnosus GG simultaneously with antibiotics reduced the incidence of symptoms of diarrhea (8% in the lactobacillus group and 26% in the placebo group) [11].
According to a meta-analysis dedicated to the evaluation of the role of various probiotics in the prevention of ADA in children, the use of L. rhamnosus GG has a statistically significant protective effect (the relative risk of developing AMA in the context of the use of this lactobacillus strain is 0.29) [12]. Similar results were obtained in two other meta-analyzes, which found that L. are the most promising probiotics that have been shown to be effective in preventing ADA in children. rhamnosus GG and yeast S. boulardii [13, 14].
According to one hypothesis, the cause of the generalized spread of food allergies is the qualitative and quantitative changes in the intestinal microflora.
The use of lactobacilli and bifidobacteria has been shown to stimulate an antiallergic response, probably due to their ability to compensate for disturbances in the composition of the microflora and to normalize the permeability of the intestinal wall [16, 17]. In addition, probiotics improve the specific IgA response and reduce the production of cytokines associated with allergic inflammation [15].
In a placebo-controlled study of 31 children 2.5 to 15.7 months of age, the efficacy of L. was evaluated. rhamnosus GG in children with atopic eczema and allergies to cow's milk. All children received a nutritious milk mixture with or without L. rhamnosus GG for 1 month. The severity of the disease was assessed on a SCORAD scale. During the evaluation after 1 month, a significant decrease in the score was observed in children receiving the probiotic (from 26 to 15 points, p = 0.008) compared to the placebo group (from 21 to 19 points, p = 0, 89) [17].
In a second randomized, double-blind, placebo-controlled study, 27 infants with atopic eczema who were breastfed were transferred to breastfeeding with a highly hydrolyzed whey formula with or without the addition of one of the two probiotic strains: L. rhamnosus GG or B. lactis BB-12 for 6 months. After 2 months, the severity score for atopic dermatitis on the SCORAD scale decreased in the two treatment groups compared to the control group (p = 0.002). Thus, the score on the scale was 16 points before the start of the study and decreased in the B. lactis BB-12 group to 0 and in the L. rhamnosus group GG at 1, against 13.4 points in the control group [18].
In another study of similar design, 230 children with atopic dermatitis or atopic eczema and suspected cow's milk intolerance clinic received either L. rhamnosus GG, or placebo for 4 weeks. Four weeks after the end of the study, 120 children received a double-blind, placebo-controlled test for cow's milk tolerance. It was found that there was no statistically significant difference in the variation of the SCORAD score between the study groups immediately after treatment and after 4 weeks. However, in children sensitized to cow's milk proteins (presence of specific IgE), the use of lactobacilli led to a more pronounced drop in the SCORAD score than in the placebo group (-26.1 vs-19.8, p = 0.036), from the initial visit to the evaluation 4 weeks after the end of treatment. The results of this study indicate that in children with an atopic eczema clinic, use L. rhamnosus GG relieves the symptoms of the disease precisely in patients with an IgE-dependent form of the disease. [19].
Thus, the use of L. rhamnosus GG and B. lactis BB-12 is effective in the treatment of atopic eczema in children.
The first study on the efficacy of probiotics for the prevention of PDI and the gastrointestinal tract in children was published in 2001 in the British Medical Journal. A multicenter, double-blind, randomized, placebo-controlled study evaluated the effectiveness of lactobacilli in preventing displacement and the gastrointestinal tract in children visiting daycare centers in Helsinki [20]. The study looked at healthy children (n = 571) aged 1 to 6 years (mean age 4.6 years) who were randomized to receive milk enriched with L. rhamnosus GG for 7 months in the fall-winter-spring period or to receive the same milk in composition, but without probiotic. It turned out that in the group of children receiving L. rhamnosus GG, there were fewer days of absence from kindergarten due to illness (4.9 vs 5.8; p = 0.03). In the lactobacillus group, the number of PDIs was lower (97 vs 123, p = 0.05), and the frequency of complicated PDIs and lower respiratory infections decreased by 17%. In addition, far fewer antibiotics for displaced people (acute otitis media, acute sinusitis, acute bronchitis and pneumonia) were prescribed in the study group compared to the control (111 vs 140, p = 0.03). The period of absence of respiratory tract symptoms was longer in the lactobacillus group compared to the control (5 vs 4 weeks, p = 0.03). At the same time, there was no significant difference in the length of the remission period for symptoms of gastrointestinal lesions (25 vs 24 weeks, p = 0.2) [20 ].
In a study in Croatia, the prophylactic efficacy of L. has been demonstrated. rhamnosus GG. In a randomized, double-blind, placebo-controlled study, children (n = 281) attending daycares were randomly assigned to receive a fermented dairy product enriched with L. rhamnosus GG (n = 139) or the same dairy product, but without lactobacilli (n = 142), for 3 months. The use of L. rhamnosus GG has been shown to significantly reduce the risk of upper respiratory tract infections (relative risk 0.66, 95% confidence interval [CI] 0, 52-0.82), reduces the risk of developing IDIs that last more than 3 days (relative risk 0.57, 95% CI 0.41-0.78) and statistically significantly reduces the number of days of symptoms respiratory tract (p less than 0.001). The results allow us to recommend the use of L. rhamnosus GG as an effective measure for the prevention of upper respiratory tract infections in children frequenting groups of children [21].
Thus, the efficacy of L. rhamnosus GG and B. lactis Bb-12 probiotics, which is part of the drug Bifiform Kids, is confirmed in the treatment of acute diarrhea. , prevention of antibiotic-associated diarrhea, treatment of food allergies and prevention of respiratory infections in pediatrics.

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