Кишечная микробиота у недоношенных детей — современное состояние проблемы (обзор литературы)

The problem of intestinal microbiota influencing the health of early aged children has become especially relevant over the past few years. On one hand, this is due to the significant worsening of the human environment ecology, on the other — due to the high prevalence of digestive disorders in children, especially premature ones. The introduction of modern high-informative molecular-genetic research methods (PCR-amplification with gene sequenation) made it possible to reveal the primary stage of human colonization by bacteria even at the stage of fetal ontogenesis and to thoroughly decode the microbiota structure in newborns and first-year babies. It is established, that the mothers microbiota has a direct effect on the quantity and quality of the child’s microbiota. The mother’s microbiota depends not only on her possessing inflammatory, but also metabolic diseases (obesity). There is also a direct correlation between the children’s microbiota and the wway they were born (microbiota is better in cases of natural birth), and these differences are prevalent after a number of months after birth. One of the main factors affecting microbiota after birth from the very first day is nutrition. Most studies earnestly confirm the role of breastfeeding in contributing to an optimal microbiocenosis in the child. Antibacterial therapy, being received by either the mother or the child has a negative effect on the colonization of the intestines by symbiont microbes. The negative impacts on the micro flora are especially significant for premature children especially those born with a very low and extremely low body mass. The ontogenesis of these children is most severed by malicious factors (infections followed by the necessity of a massive antibacterial therapy, hypoxia, surgical birth, forced artificial feeding) in connection with a general immaturity, including not yet fully-fledged body defense systems. Directive microbiota correction in premature children is an important condition for prevention and treatment of such severe diseases as sepsis necrotizing enterocolitis. For this reason, the usage of probiotics is considered as one of the promising practices of practical neonatology. The article contains an example of studying the effectiveness of probiotic therapy in premature babies with a combined perinatal pathology.Проблема влияния микробиоты кишечника на состояние здоровья детей раннего возраста приобрела особую актуальность в последние годы. Это связано, с одной стороны, со значительным ухудшением экологии среды обитания человека, с другой — с высокой частотой расстройств пищеварения у детей, особенно родившихся преждевременно. Внедрение современных высокоинформативных молекулярно-генетических методов исследования (ПЦР-амплификация с секвенированием генов) позволило выявить начальный этап микробной колонизации человека еще в периоде внутриутробного онтогенеза и подробно расшифровать структуру микробиоты у новорожденных и младенцев 1-го года жизни. Установлено, что на количественную выраженность и качественный состав кишечной микробиоты влияет состав микробиоты матери, который зависит от наличия/отсутствия у нее не только воспалительных, но и метаболических болезней (ожирения). Обнаружено, что имеется достоверная связь состава микробиоты у младенцев со способом родоразрешения их матерей (более благоприятный состав после естественных родов), причем указанные различия сохраняются на протяжении нескольких месяцев после рождения. Один из основных факторов, влияющих на микробиоту с первых дней, — питание; большинство исследований убедительно подтверждают роль грудного вскармливания в становлении оптимального микробиоценоза у младенца. Антибактериальная терапия, получаемая матерью и/или ребенком, оказывает негативное воздействие на колонизацию кишечника микробами-симбионтами. Негативные внешние влияния на микробиоту особенно значимы у недоношенных детей, прежде всего у родившихся с очень низкой и экстремально низкой массой тела. Онтогенез этих младенцев наиболее отягощен вредными факторами (инфекцией и необходимостью массивной антибактериальной терапии, гипоксией, оперативным родоразрешением, вынужденным искусственным вскармливанием) на фоне общей незрелости, в том числе несформированности защитных механизмов организма. Направленная коррекция микробиоты у недоношенных детей является важным условием профилактики и лечения таких грозных заболеваний, как сепсис и некротизирующий энтероколит. Именно поэтому использование препаратов-пробиотиков представляется одним из перспективных направлений практической неонатологии. В статье приводится пример исследования эффективности пробиотикотерапии у недоношенных детей с сочетанной перинатальной патологией

Дизонтогении микробиоты кишечника у детей первых месяцев жизни как фактор формирования атопии

The article describes the modern views on the relationship between altered development of gut microbiota in infants and the risk of developing atopic diseases (atopic dermatitis and bronchial asthma). The studies of genetic susceptibility to atopy and the influence of epigenetic mechanisms involved in the regulation of gene expression responsible for the hyperproduction of immunoglobulin E are discussed. The characteristics of the microbiota of infants with already developed atopic diseases and children at risk of atopy are analyzed. In infants who subsequently developed atopy, the composition of gut microbiota at the birth is characterized by a reduced abundance of bifidobacteria  and high content of potentially pathogenic microorganisms.  The triggering role of active metabolites of altered microbiota on the differentiation of T-regulatory  cells has been established.  A preventive effect of optimal breastfeeding has been confirmed: meta-analyzes of recent studies indicate a link between the duration of breastfeeding  and a decrease in the frequency of bronchial asthma. The microbiota of breast milk contributes to the proper development of the infant’s microbiota, determines its diversity and immunomodulating action. On the basis of the conducted research, methods of targeted correction of the intestinal microbiota in children with risk of atopy can be developed.В статье отражены  современные взгляды  на связь формирования  микробиоты кишечника у детей первого  года жизни с риском развития атопических заболеваний (атопического дерматита и бронхиальной астмы). Обсуждаются исследования  генетической  предрасположенности к атопии и влияния эпигенетических  факторов  на регуляцию экспрессии генов, ответственных за гиперпродукцию иммуноглобулинов  класса Е. Проанализированы  характеристики микробиоты младенцев с уже развившимися атопическими заболеваниями и детей из группы риска по атопии. У детей, впоследствии  сформировавших атопию, состав микробиоты кишечника при рождении  характеризуется сниженным содержанием бифидобактерий и высоким — условно-патогенных микроорганизмов. Установлена триггерная роль активных метаболитов измененной микробиоты в трансформации Т-регуляторных клеток. Подтверждена превентивная  роль  адекватного  грудного  вскармливания:  метаанализы  исследований  последних лет  свидетельствуют  о связи продолжительности грудного  вскармливания  со снижением  частоты бронхиальной астмы. Микробиота грудного молока способствует адекватному формированию микробиоты младенца, определяет ее разнообразие и иммуномодулирующее действие. На основе проведенных исследований могут быть разработаны методы направленной коррекции кишечной микробиоты у детей группы риска по атопии

ЗНАЧЕНИЕ ГРУДНОГО ВСКАРМЛИВАНИЯ В ПРОФИЛАКТИКЕ ОТДАЛЕННЫХ НАРУШЕНИЙ МЕТАБОЛИЗМА: ОБЗОР ЛИТЕРАТУРЫ

The literature review is dedicated to the preventive role of breastfeeding in preserving long-term health of individuals and the population in whole. The issue is urgent due to high prevalence of multifactor metabolic diseases (obesity, pancreatic diabetes, hypertonic disease etc.) in adolescents and adults; these socially significant have started to set on in younger persons in the recent years. The article presents results of the studies dedicated to the association between the nature of the infant's feeding and risk of metabolic pathology conducted in the recent decades in various countries. Most works put premature infants in the high risk group, as the diets involving special formulas contributing to "catching-up" growth of neonates with low birth weight are statistically significantly associated with high risk of long-term cardiovascular diseases. According to numerous studies, artificial feeding significantly increases the risk of excess weight and obesity, hypertonic disease and atherogenic dyslipidemia. Possible mechanisms of realization of hereditary susceptibility to metabolic disorders in the setting of artificial feeding are enhanced insulin burst paired with further development of insulin resistance; preventive role of breast milk is associated with the hormones therein, which program the individual's metabolism. Along with that, breastfeeding provides metabolic and immunological programming by means of forming optimal intestinal microbiota in a child. All the studies indicate importance of prolonged breastfeeding during infancy, which is why medical administrative support provided by medical personnel of medical and preventive facilities is important for preventing hypolactasia. District pediatricians and nurses not only control, but also organize the process of breastfeeding; when necessary, they recommend special devices intended to optimize lactation (breast pumps, nipple shields); if breast latching is not feasible – feeding with extracted breast milk using bottles and pacifiers reproducing natural breast sucking mechanism. Обзор литературы посвящен оценке профилактической роли грудного вскармливания в обеспечении отдаленного здоровья индивидуума и популяции в целом. Актуальность проблемы обусловлена высокой распространенностью мультифакториальных метаболических заболеваний (ожирения, сахарного диабета, гипертонической болезни и др.) у подростков и взрослых; в последние годы отмечена тенденция к омоложению возраста дебюта этих социально-значимых заболеваний. Приводятся результаты исследований, выполненных в последние десятилетия в различных странах и посвященных связи характера вскармливания ребенка на первом году жизни со степенью риска реализации метаболической патологии. В большинстве работ указывается, что в группе особого риска находятся недоношенные дети, поскольку диеты с использованием специальных смесей, способствующих «догоняющему» росту маловесных новорожденных, статистически достоверно были связаны с высоким риском отдаленных сердечно-сосудистых заболеваний. Искусственное вскармливание, как установлено многочисленными исследованиями, значимо повышает риск формирования избыточного веса и ожирения, а также гипертонической болезни, атерогенной дислипидемии. К возможным механизмам реализации наследственной предрасположенности метаболических расстройств на фоне искусственного вскармливания относят усиленный выброс инсулина с последующим формированием инсулинорезистентности; профилактическая роль грудного молока связывается с наличием в нем гормонов, обладающих программирующим воздействием на метаболизм индивидуума. Наряду с этим метаболическое и иммунологическое программирование при грудном вскармливании осуществляется через формирование оптимальной микробиоты кишечника ребенка. Все исследования свидетельствуют о важности пролонгирования грудного вскармливания на протяжении первого года жизни, поэтому в профилактике гиполактазии важную роль играет медико-организационная поддержка, которую оказывают медицинские работники лечебно-профилактических учреждений. Участковый педиатр и медицинская сестра не только контролирует, но и организуют процесс грудного вскармливания; при необходимости рекомендуют специальные приспособления, оптимизирующие лактацию (молокоотсосы, накладки для соска), в случае невозможности прикладывания к груди — вскармливание сцеженным грудным молоком с использованием бутылочек и сосок, воспроизводящих механизм естественного сосания из груди

Intestinal Microbiota in Premature Children — the Modern State of the Problem (Literature Analysis)

The problem of intestinal microbiota influencing the health of early aged children has become especially relevant over the past few years. On one hand, this is due to the significant worsening of the human environment ecology, on the other — due to the high prevalence of digestive disorders in children, especially premature ones. The introduction of modern high-informative molecular-genetic research methods (PCR-amplification with gene sequenation) made it possible to reveal the primary stage of human colonization by bacteria even at the stage of fetal ontogenesis and to thoroughly decode the microbiota structure in newborns and first-year babies. It is established, that the mothers microbiota has a direct effect on the quantity and quality of the child’s microbiota. The mother’s microbiota depends not only on her possessing inflammatory, but also metabolic diseases (obesity). There is also a direct correlation between the children’s microbiota and the wway they were born (microbiota is better in cases of natural birth), and these differences are prevalent after a number of months after birth. One of the main factors affecting microbiota after birth from the very first day is nutrition. Most studies earnestly confirm the role of breastfeeding in contributing to an optimal microbiocenosis in the child. Antibacterial therapy, being received by either the mother or the child has a negative effect on the colonization of the intestines by symbiont microbes. The negative impacts on the micro flora are especially significant for premature children especially those born with a very low and extremely low body mass. The ontogenesis of these children is most severed by malicious factors (infections followed by the necessity of a massive antibacterial therapy, hypoxia, surgical birth, forced artificial feeding) in connection with a general immaturity, including not yet fully-fledged body defense systems. Directive microbiota correction in premature children is an important condition for prevention and treatment of such severe diseases as sepsis necrotizing enterocolitis. For this reason, the usage of probiotics is considered as one of the promising practices of practical neonatology. The article contains an example of studying the effectiveness of probiotic therapy in premature babies with a combined perinatal pathology

INTRODUCTION OF SUCCESSFUL BREASTFEEDING PRINCIPLES TO THE SYSTEM OF MEDICAL CARE DELIVERY TO PREMATURE INFANTS

Optimal feeding in the early postnatal ontogenesis is especially important for premature infants with overlapping perinatal pathologies. As is known, unique properties of breast milk ensure adequate physical and neuropsychic development of children, as well as balanced development of metabolism; this is especially important for premature infants. The article presents the main stages of securing priority of breastfeeding for healthy infants: the history of development of the commonly known “ten steps” of breastfeeding for obstetric institutions and the objective impediments to implementation of these steps at neonatal resuscitation and intensive care units (NRICUs) and neonatal pathology units. A group of experts of the World Health Organization summarized experience of several neonatal inpatient hospitals in the framework of the Baby Friendly Hospital Initiative and formulated the basic principles of breastfeeding support for implementation at NRICUs. The experts emphasize utmost importance of a long-lasting contact with the mother (skin-to-skin) and teaching lactation preservation methods to mothers for the support of breastfeeding of premature infants. An attitude toward withdrawal from other feeding methods, rubber teats and pacifiers, as well as organization of breastfeeding “upon request” from premature infants is restricted due to peculiarities of health status and physiological maturity of such children. The experts state that mothers must remain with premature infants around the clock and the necessity of contact with other family members. They also emphasize the importance of preparation of parents to breastfeeding maintenance after discharge from hospital. Implementation of these modified approaches is expected to contribute to successful prolonged breastfeeding of premature infants

Gut microbiota dysontogeniya in infants as a factor in the development of atopy

The article describes the modern views on the relationship between altered development of gut microbiota in infants and the risk of developing atopic diseases (atopic dermatitis and bronchial asthma). The studies of genetic susceptibility to atopy and the influence of epigenetic mechanisms involved in the regulation of gene expression responsible for the hyperproduction of immunoglobulin E are discussed. The characteristics of the microbiota of infants with already developed atopic diseases and children at risk of atopy are analyzed. In infants who subsequently developed atopy, the composition of gut microbiota at the birth is characterized by a reduced abundance of bifidobacteria  and high content of potentially pathogenic microorganisms.  The triggering role of active metabolites of altered microbiota on the differentiation of T-regulatory  cells has been established.  A preventive effect of optimal breastfeeding has been confirmed: meta-analyzes of recent studies indicate a link between the duration of breastfeeding  and a decrease in the frequency of bronchial asthma. The microbiota of breast milk contributes to the proper development of the infant’s microbiota, determines its diversity and immunomodulating action. On the basis of the conducted research, methods of targeted correction of the intestinal microbiota in children with risk of atopy can be developed

ROLE OF BREASTFEEDING IN PREVENTING LONG-TERM METABOLIC DISORDERS: REVIEW

The literature review is dedicated to the preventive role of breastfeeding in preserving long-term health of individuals and the population in whole. The issue is urgent due to high prevalence of multifactor metabolic diseases (obesity, pancreatic diabetes, hypertonic disease etc.) in adolescents and adults; these socially significant have started to set on in younger persons in the recent years. The article presents results of the studies dedicated to the association between the nature of the infant's feeding and risk of metabolic pathology conducted in the recent decades in various countries. Most works put premature infants in the high risk group, as the diets involving special formulas contributing to "catching-up" growth of neonates with low birth weight are statistically significantly associated with high risk of long-term cardiovascular diseases. According to numerous studies, artificial feeding significantly increases the risk of excess weight and obesity, hypertonic disease and atherogenic dyslipidemia. Possible mechanisms of realization of hereditary susceptibility to metabolic disorders in the setting of artificial feeding are enhanced insulin burst paired with further development of insulin resistance; preventive role of breast milk is associated with the hormones therein, which program the individual's metabolism. Along with that, breastfeeding provides metabolic and immunological programming by means of forming optimal intestinal microbiota in a child. All the studies indicate importance of prolonged breastfeeding during infancy, which is why medical administrative support provided by medical personnel of medical and preventive facilities is important for preventing hypolactasia. District pediatricians and nurses not only control, but also organize the process of breastfeeding; when necessary, they recommend special devices intended to optimize lactation (breast pumps, nipple shields); if breast latching is not feasible – feeding with extracted breast milk using bottles and pacifiers reproducing natural breast sucking mechanism

Predictors of Cognitive Defects and Its Prevention Capabilities in Premature Infants

The article summarizes the materials of modern publications on cognitive development of premature infants in connection with perinatal factors and parenting conditions. Leading risk predictors of cognitive defects in premature infants are severe dysmaturity by the time of birth (gestational age <27 weeks) and need for intensive care during the first weeks of life. The data of longitudinal researches of the premature infants’ development until reaching their adulthood is presented. The structure of cognitive defects in this population is studied. The most common problems were revealed in learning mathematics, operational memory and purposeful behavior and activity. Frequency of these cognitive defects is associated with both: stage of prematurity social problems of the family. Modern neurovisualization methods (diffusion weighted imaging and functional magnetic resonance imaging (MRI) of the brain) allows to identify the defects in child nervous system (Connectome) development already at the age of 18 months. It can be the substrate of cognitive defects, and it will allow to predict individual development pathway and implement direct corrections and interventions

THE DEVELOPMENT OF DONATED BREAST MILK BANKS IN RUSSIA: NECESSITY AND POSSIBILITIES. SURVEY RESULTS WITHIN THE PILOT PROJECT OF A DONATED BREAST MILK BANK POWERED BY THE FEDERAL STATE BUDGETARY SCIENTIFIC INSTITUTION «SCIENTIFIC CENTRE OF CHILDREN’S HEAL

A child should receive the donated breast milk when a mother cannot provide it. The United Association of Perinatal Care resolution underlines that the creation of donated breast milk banks pursuits the national policy for the support and popularization of breast feeding. The article presents the results of survey among mothers, fathers and medical workers regarding necessity and possibility of developing donated breast milk banks in Russia. The respondents showed low awareness of the benefits and safety of the donor breast milk for children with deficiency or lack of the mother's milk. Received data points out the necessity of promotion of donated breast milk banks in order to stimulate breast feeding as well as to raise the awareness of breast feeding necessity