Formation of intestinal microflora in children during the first year of their life

In 525 young children the state of intestinal microbiocenosis was studied every month of the first year their life. The study revealed that the process of the microflora formation lasted throughout the first year of their life and was characterized by dysbiotic disturbances. During this period the aggravation of dysbiotic changes in the intestine of these children on months 3, 6-7 and 11-12 was of particular importance. The formation of stable dysbacteriosis led to a decrease in the immunological status of the child, which was manifested by the increased content of such microorganisms as hemolytic cocci, Proteus and a decrease in the quantitative level of bifidobacteria in the total intestinal microbiocenosis by the end of the first year of child's life.     

New experimental models in microbial ecology

Peculiar features of dysbiosis development in persons under extreme conditions were studied. It was shown that a number of extreme factors participated in formation of dysbiotic disorders in intestinal microflora. Of paramount importance was the neuro-emotional stress. Lability of bifido- and lactoflora was considered as the starting mechanism in dysbacteriosis under the extreme conditions. In the experimental models with rats SPF and Primates during flights of biosatellites of the Kosmos series the role of indigenous++ microflora in maintaining the microecological homeostasis, as well as the need for development of artificial and controlled intestinal microflora promising in prophylaxis of dysbacteriosis under extreme conditions was shown. The theoretical and experimentally grounded necessity of maintaining constant intestine microbiocenosis was confirmed by the practice of using the system of measures for recovery, stabilization and optimization of microflora in persons under extreme conditions.     

The autologous intestinal microflora in the postresuscitation period after acute blood loss in rats

In this work the data obtained in the study of intestinal microbiocenosis in rats on the third day of the postresuscitation period after acute blood loss are presented. The quantitative and qualitative shifts of microflora at different biotopes, such as the wall of the small intestine, the parietal microflora of Peyer's patches, the contents and wall of the large intestine, have been characterized. Some specific features of dysbiotic changes have been revealed in comparison with the shifts of intestinal microflora in cases of dysbacteriosis caused by other reasons. The translocation of different microorganisms, including Bacterium bifidum and lactobacilli, into mesenteric lymph nodes, the liver, the spleen and the blood has been observed.     

Role of dysbacteriosis in the formation of chronic noninfectious pathology in children

The results of clinical observations and laboratory data make it possible to regard dysbacteriosis as an important factor in the pathogenesis of chronic noninfectious pathology in children. The adequate complex correction of intestinal dysbacteriosis on the basis of probiotic therapy facilitates the prolonged remission of the disease in children with diabetes mellitus of type 1 (DM1) and myopathy, decreases severity of late complications of DM1. A suggestion is made on the role of dysbiotic microflora in the development of chronic non-infectious pathology in children.     

菌群失调小鼠感染鼠伤寒沙门菌后Th1和Th2细胞因子的动态研究

目的研究鼠伤寒沙门菌感染小鼠在菌群失调下Th细胞因子的动态变化,以探讨菌群失调对沙门菌感染的免疫机制。方法分别建立菌群失调、感染和空白对照的小鼠模型。各组动物在感染不同时点处死,观察小肠、肝脏和脾脏病理改变。采用流式细胞仪检测脾脏细胞中IFN-γ和IL-4表达,以此代表Th1和Th2细胞。结果菌群失调组病理损害最重,Th1明显增加,表达水平高,Th2变化不大,Th1/Th2比值升高。结论菌群失调后,能够加重小鼠感染鼠伤寒沙门菌引起的的Th1型反应,产生炎症性损伤。     

Clinical and diagnostic importance of the evaluation of the Ig proteases activity in children with intestinal dysbacteriosis

The specific activity of serine, metal dependent and thiolic Ig proteases in the coprofiltrates of children with manifestations of intestinal dysbacteriosis was determined by the enzyme immunoassay. 56 children with pronounced symptoms of intestinal disorders (37 children aged up to 1 year and 19 children over 1 year) were examined. A group of 25 clinically healthy children was used as control. Simultaneously with protease activity of coprofiltrates, there was detected the level of Ig-degrading activity of the opportunistic bacteria islolates of different taxonomic groups from feces of children with dysbacteriosis of different severity (as determined by the classical bacteriological method). The evaluation of the Ig-proteolytic activity of fecal supernatants, associated with the presence of serine, metal-dependent and thiolic proteases in the intestine, as well as detection of such proteases in microbial isolates, seems to be highly important for the diagnosis of intestinal disorders in children and is recommended for screening of intestinal dysbacteriosis.     

Microflora of the large intestine in patients with connective tissue dysplasia

The specific features of intestinal aerobic and anaerobic intestinal microflora in children with nondifferentiated connective tissue dysplasia were under study. A high rate of dysbiotic disturbances was noted in patients with connective tissue dysplasia in comparison with healthy persons. Profound quantitative and qualitative changes in the biocenosis of the intestine were detected in patients with the pathology of the gastrointestinal tract as well as that of the locomotor system. Changes in the species composition and the persistence properties of the intestinal microflora may serve as pathogenetic factors in the development of connective tissue dysplasia.     

Treatment of intestinal dysbacteriosis in children with diabetes mellitus]

The use of the probiotic Acylact in combination with Viferone containing human recombinant interferon-alpha 2 in the treatment of intestinal dysbacteriosis in children with insulin-dependent diabetes mellitus (IDDM) was shown to be highly efficient. Elimination of microecologic disorders in the intestine was accompanied in all the children by immune rearrangements. The quantity of secretory and serum immunoglobulins and complement increased and the white blood cell chemiluminescence proved to be higher. The correction of the immune status of the children with IDDM resulted in a certain decrease of glycemia. The data are indicative of the fact that such a treatment of intestinal dysbacteriosis in children with IDDM is promising.     

The frequency of staphylococcal colonization of the intestines in children with the manifestations of dysbacteriosis

In 2100 children of different age groups the microbiocenosis of the large intestine was studied. The study revealed that the colonization of the mucous membrane of the large intestine with staphylococci developed in 30% of children with intestinal dysbacteriosis. Young children were mainly affected (91%). The prevailing species among isolated staphylococci was S. aureus (86%), capable of persistence in the intestine (30.9%). In children non typing S. aureus strains mainly circulated (70%), and among phage-typing strains isolates of phage group III prevailed (70.2%). The colonization of the intestine with coagulase-negative staphylococci was possible (14%). Microecological intestinal disturbances in children of different age groups were characterized by different degrees of changes in normal microflora with the prevalence of opportunistic microorganisms in the microbial picture.     

Dysbacteriosis in patients with colon polyposis

The study revealed the most profound changes in the composition of intestinal microflora in patients with polyposis of the large intestine. In these patients anaerobic microflora (bifidobacteria, lactic acid bacteria) was more often suppressed than in other examined groups, in particular, patients with cholelithic disease. The associations of hemolytic Escherichia with Klebsiella pneumoniae, Pseudomonas aeruginosa, Citrobacter freundii were often observed as well as the increased content of enterococci and fungi of the genus Candida. The determination of frequency and degree of manifestations showed that dysbacteriosis was registered in the absolute majority of patients (97.4%) with polyposis of the large intestine. Among patients with cholelithic disease disturbances in microbiocenosis were detected in 60.0% of cases, the profundity and character of the microflora composition changes being less pronounced.     

Microflora of the upper respiratory tract of normal young children and in respiratory tract diseases. Normal microflora and dysbiosis at different levels of the upper respiratory tract in healthy children and pneumonia patients

Material obtained from the mucous membranes of the upper respiratory tract (the anterior section of the nasal cavity, the fauces) in young children, both healthy and suffering with different forms of acute pneumonia, has been analyzed with due regard to the structure of the microflora, its specific composition and the size of populations formed by different species constituting the microflora. This analysis has made it possible to determine the species constituting normal microflora, to detect its dysbiotic changes, and to determine their degree (partial or complete dysbacteriosis). The degree of pathologic changes in the microecological balance of the upper respiratory tract has been shown to reflect the severity of acute pneumonia and to be determined by the characteristics of the natural resistance system in young children.     

Microbiocenosis of the large intestine in acute complicated pneumonia in children

Fifty-six children of early age with pneumonia developed on the background of frequent respiratory infections were placed under observation. In 91.1% of these cases microecological disturbances in the intestine were detected, 46.6% of the patients having third-degree dysbacteriolysis. In such cases it is more correct to regard the "intestinal" syndrome as the clinical manifestation of disturbances in the biocenosis of the intestine, the state of its microflora. Intestinal dysbacteriosis aggravates the course of acute aggravated pneumonia in children and requires the inclusion of special therapy aimed at normalizing intestinal microflora.     

Bacterial endotoxinemia in children with intestinal dysbacteriosis

34 children with gastrointestinal diseases of infectious, allergic and mixed etiology were examined. The state of normal microflora in the large intestine as indicated by fecal bacterial charts and the level of secretory immunoglobulin A (sIgA) in the contents of the intestine as indicated by the results of radial immunodiffusion were studied. In addition, the content of endotoxin in the children's plasma was determined with the use of the Limulus (LAL) test. The presence of endotoxin in the plasma of children with intestinal dysbiosis was determined in 71.1% of cases. The frequency of the detection of antigenemia was found to be related to the severity of manifestations of dysbiotic changes in the intestine and to the level of sIgA in fecal supernatants. The inclusion of the probiotic preparation Bifidumbacterin forte containing live bifidobacteria adsorbed on activated charcoal into the complex therapy of digestive tract diseases ensured a decrease in the detection rate of endotoxinemia, which correlated with the tendency towards the normalization of defective intestinal microflora.     

Effects of ceftriaxone‐induced intestinal dysbacteriosis on dendritic cells of small intestine in mice

Intestinal microflora plays a pivotal role in the development of the innate immune system and is essential in shaping adaptive immunity. Dysbacteriosis of intestinal microflora induces altered immune responses and results in disease susceptibility. Dendritic cells (DCs), the professional antigen‐presenting cells, have gained increasing attention because they connect innate and adaptive immunity. They generate both immunity in response to stimulation by pathogenic bacteria and immune tolerance in the presence of commensal bacteria. However, few studies have examined the effects of intestinal dysbacteriosis on DCs. In this study, changes of DCs in the small intestine of mice under the condition of dysbacteriosis induced by ceftriaxone sodium were investigated. It was found that intragastric administration of ceftriaxone sodium caused severe dysteriosis in mice. Compared with controls, numbers of DCs in mice with dysbacteriosis increased significantly (P = 0.0001). However, the maturity and antigen‐presenting ability of DCs were greatly reduced. In addition, there was a significant difference in secretion of IL‐10 and IL‐12 between DCs from mice with dysbacteriosis and controls. To conclude, ceftriaxone‐induced intestinal dysbacteriosis strongly affected the numbers and functions of DCs. The present data suggest that intestinal microflora plays an important role in inducing and maintaining the functions of DCs and thus is essential for the connection between innate and adaptive immune responses.     

The effect of enterococci on normalizing the intestinal microflora in experimental dysbacteriosis

The normal microflora of the intestine produces essential influence on the vital activity of the host. The exposure of the body to the action of different unfavorable factors (roentgen radiation, the administration of antibiotics, Salmonella infection, etc) results in changes in the normal microflora of the gastrointestinal tract. This work was aimed at the study of the influence of Streptococcus faecium YDC-48 on the intestinal microflora of mice in experimental (chemotherapeutic, postirradiation) dysbacteriosis and Salmonella infection. The effect of the oral administration of S. faecium YDC-48 on the correction of the intestinal microflora of mice in cases of dysbacteriosis etiology was studied. The intragastric administration of S. faecium YDC-48 was found to induce an increase in the level of lactobacterin and a decrease in the number of opportunistic microorganisms in chemotherapeutic and postirradiation dysbacteriosis. The oral administration of S. faecium YDC-48 decreased the manifestations of intestinal dysbacteriosis in experimental Salmonella infection. The possibility of developing a preparation on the basis of S. faecium YDC-48, a representative of normal intestinal microflora, is discussed.     

The microbiological characteristics of intestinal dysbacteriosis in children and adults in the city of Moscow

The bacteriological analysis of 302 children has revealed that dysbacteriosis with the increased content of hemolytic Escherichia in the intestine develops more frequently in the presence of the deficiency of bifido- and lactobacteria. The development of other kinds of dysbacteriosis with the increased content of different opportunistic enterobacteria, staphylococci, enterococci and fungi, as well as dysbacteriosis with the decreased content of Escherichia, does not practically depend on the deficiency of bifido- and lactobacteria. In patients with the increased content of Escherichia an increase in the content of opportunistic enterobacteria, staphylococci and fungi is observed more frequently than in patients with the low content of Escherichia.     

胃转流术对2型糖尿病患者近期肠道菌群的影响

目的研究2型糖尿病患者行胃转流术前后肠道菌群是否发生变化。方法收集30例2型糖尿病患者术前和术后粪便,测肠道菌群,以25例健康志愿者的粪便为对照组。结果 2型糖尿病患者的肠杆菌较健康人增多,双歧杆菌较正常人减少,胃转流术后双歧杆菌增加,肠杆菌减少。结论 2型糖尿病患者出现肠道菌群失调,胃转流术后控制了血糖,双歧杆菌数量增加。     

Dynamics of the establishment of intestinal microflora in healthy full-term newborns]

A study was made of the dynamics of establishment of the intestinal microflora in 79 healthy mature neonates born of healthy mothers. A total of 223 bacteriological examinations were conducted. A stable prevalence of bifidobacteria over the aerobic portion of the intestinal biocenosis occurred in all the children from the 8th day after birth. Along with this the following bacteria were continuously present in the intestine: lactic bacilli and streptococci E. coli, enterococci and staphylococci; however, their portion in the biocenosis was not great. Bacteroids, microbes of the Proteus genus, and yeast-like fungi were found in the cultures only before the establishment of a high bifidobacteria level. Conditionally pathogenic microorganisms and their associations were continuously revealed in 19.8% of healthy mature neonates. Apparently the qualitative prevalence of bifidobacteria prevented the clinical expression of dysbacteriosis in these children.     

Microecological aspects of small intestinal bacterial overgrowth syndrome

Small intestinal bacterial overgrowth syndrome (SIBOS) means chronic recurrent diarrhea with malabsorption, intoxication and increased risk of endogenous infection. This syndrome are accompanied by increase of overall bacterial burden in biotope >10(5) CFU/ml in adults and >10(4) CFU/ml in children, emergence of different species of enterobacteria, bacteroides, clostridia and fusobacteria et al. in small intestine. Such characteristics of the syndrome allow to consider it as syndrome of disturbances of intestinal microflora (dysbacteriosis). Microecological changes are accompanied by B12 vitamin deficiency anemia, hypovitaminosis, protein deficiency, translocation of bacteria and their toxins from intestine in blood, emergence of endotoxinemia and possible generalization of infection. SIBOS is diagnosed by concentration of hydrogen in expiratory flow (lactulosa load test) or by bacteriological study of aspirate from proximal part of small intestine. Complex treatment includes containing lacto- and bifidobacteria probiotics and, in more severe cases, antimicrobial agents (vancomycine, metronidazole, aminoglycosides, amoxicillin clavulanate, tetracycline, and cephalosporines of 2nd generation) with following correction of disturbed microbiocenosis by different probiotics.     

Possible use of total blood analysis for diagnosis of intestinal dysbacteriosis accompanied by bacteremia

Possible application of total blood analysis in the diagnosis of intestinal dysbacteriosis of the 2nd--3d degree, accompanied by bacteriemia, is substantiated. The proposed method includes the calculation of tentative coefficients of peripheral blood characteristics. These coefficients reflect changes in the intestinal microbiocenosis and make it possible to make conclusions on the presence of bacteriemia. This method is recommended for use as the screening test in the laboratory diagnostics of bacteriemia.