Pediatrics. Consilium MedicumPediatrics. Consilium MedicumПедиатрия. Consilium Medicum2658-66302658-6622Consilium Medicum10956310.26442/26586630.2022.2.201551ArticlesСтатьиReview ArticleProblems of gut microbiota formation as a risk factor for the development of immunopathological diseases and opportunities for their prevention: A reviewПроблемы становления кишечной микробиоты как фактор риска развития иммунопатологических заболеваний и возможности их профилактикиhttps://orcid.org/0000-0003-2743-1460KornienkoElena A.КорниенкоЕлена Александровна
Russian Federation

D. Sci. (Med.), Prof., Saint Petersburg State Pediatric Medical University

д-р мед. наук, проф., проф. каф. детских болезней им. проф. И.М. Воронцова фак-та послевузовского и дополнительного профессионального образования ФГБОУ ВО СПбГПМУ

elenkornienk@yandex.ruSaint Petersburg State Pediatric Medical UniversityФГБОУ ВО «Санкт-Петербургский государственный педиатрический медицинский университет» Минздрава России3007202221741792907202229072022Copyright ©; 2022, Consilium MedicumCopyright ©; 2022, ООО "Консилиум Медикум"2022Consilium MedicumООО "Консилиум Медикум"https://creativecommons.org/licenses/by-nc-sa/4.0https://pediatria.orscience.ru/2658-6630/article/view/109563

The formation of infant intestinal microbiota begins in the womb when there is a selective transport of certain bacteria from the intestine through the placenta and amniotic fluid which has been proved in experiments. The mode of delivery has a significant impact on the establishment of the intestinal biocenosis: babies born by caesarean section show a slower colonisation rate and a higher risk of developing food allergies later in life. Antibiotic therapy at an early age can permanently alter the composition of the intestinal microbiota and has a proven risk of developing a range of diseases, both immunopathological and metabolic. The type of feeding also has a significant impact. Exclusive breastfeeding from birth promotes the establishment of a bifidobacterial and bacteroide-dominated infant microbiota. Supplementation at birth and early transfer to complementary feeding contribute to microbiocenosis alteration and sensitisation to cow's milk protein. Probiotics due to their protective and immunomodulatory effects can improve the composition of the microbiota of breast milk and the baby's gut and their perinatal administration reduces the risk of food allergies and other diseases.

Формирование кишечной микробиоты младенца начинается еще в утробе матери, когда происходит селективная транспортировка некоторых бактерий из кишечника через плаценту и амниотическую жидкость, что доказано в экспериментах. Существенное влияние на становление кишечного биоценоза оказывает способ родоразрешения: дети, рожденные путем кесарева сечения, демонстрируют замедленные темпы колонизации и более высокий риск развития в дальнейшем пищевой аллергии. Антибиотикотерапия в раннем возрасте может надолго изменить состав кишечной микробиоты и имеет доказанный риск развития целого ряда заболеваний, как иммунопатологических, так и метаболических. Существенное влияние оказывает и вид вскармливания. Исключительно грудное вскармливание с рождения способствует становлению младенческой микробиоты с доминированием бифидобактерий и бактероидов. Докармливание молочной смесью в роддоме и ранний перевод на искусственное вскармливание способствуют альтерации микробиоценоза и сенсибилизации к белку коровьего молока. Пробиотики благодаря своему защитному и иммуномодулирующему действию способны улучшить состав микробиоты грудного молока и кишечника ребенка, их перинатальное назначение уменьшает риск развития пищевой аллергии и других заболеваний.

intestinal microbiotacolonizationprobioticsLactobacillus rhamnosus GGBifidobacterium animalis lactis Bb12кишечная микробиотаколонизацияпробиотикиLactobacillus rhamnosus GGBifidobacterium animalis lactis Bb12Dong TS, Gupta A. Influence of early life, diet and the environment on the microbiome. Clin Gastroenterol Hepatol. 2018;21(11):5-17.Arboleya S, Binetti A, Salazar N, et al. Establishment and development of intestinal microbiota in preterm neonates. FEMS Microbiol Ecol. 2012;79:763-72.Zaidi AZ, Moore SE, Okala SG. Impact of maternal nutritional supplementation during pregnancy and lactation on the infant gut or breastmilk microbiota: A systematic review. Nutrients. 2021;13:1137-62.Timmerman HM, Rutten NBMM, Boekhorst J, et al. Intestinal colonisation patterns in breastfed and formula-fed infants during the first 12 weeks of life reveal sequential microbiota signatures. Sci Rep. 2017;7.Pannaraj PS, Li F, Cerini C, et al. Association Between Breast Milk Bacterial Communities and Establishment and Development of the Infant Gut Microbiome. JAMA Pediatr. 2017;171:647.Stewart CJ, Ajami NJ, O’Brien JL, et al. Temporal development of the gut microbiome in early childhood from the TEDDY study. Nature. 2018;62:82-92.Jimenez E, Marin ML, Martin R, et al. Is meconium from healthy newborns actually sterile? Res Microbiol. 2008;159:187-93.DiGiulio DB, Romero R, Amogan HP, et al. Microbial Prevalence, Diversity and Abundance in Amniotic Fluid During Preterm Labor: A Molecular and Culture-Based Investigation. PLoS ONE. 2008:e3056.Collado MC, Rautava S, Aakko J, et al. Human gut colonisation may be initiated in utero by distinct microbial communities in the placenta and amniotic fluid. Sci Rep Sep. 2016;6:23129.Epstein FH, Goldenberg RL, Hauth JC, Andrews WW. Intrauterine Infection and Preterm Delivery. N Engl J Med. 2000;342:1500-7.Приходченко Н.Г. Клинико-патогенетические механизмы формирования аллергии к белку коровьего молока у детей первого года жизни: автореф. дис. … д-ра мед. наук. М., 2020 [Prikhodchenko NG. Kliniko-patogeneticheskie mekhanizmy formirovaniia allergii k belku korov'ego moloka u detei pervogo goda zhizni: avtoref. dis. … d-ra med. nauk. Moscow, 2020 (in Russian)].Petersen C, Dai DLY, Bouth RCT, et al. A rich meconium metabolome in human infants is associated with early life gut microbiota composition and reduced allergic sensitization. Cell Reports Medicine. 2021;2:100280.Backhed F, Roswall J, Peng Y, et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe. 2015:17.Martin R, Makino H, Yavuz AC. Early-Life events, including mode of delivery and type of feeding, siblings and gender, shape the developing gut microbiota. PLoS ONE. 2016;11:e0158498.Chu DM, Ma J, Prince AL, et al. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat Med. 2017;23:314-26.Dominguez-Bello MG, Costello EK, Contreras M, et al. Delivery mode shapes the acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc Natl Acad. Sci U S A. 2010;107:11971-5.Nagpal R, Tsuji H, Takahashi T, et al. Sensitive Quantitative Analysis of the Meconium Bacterial Microbiota in Healthy Term Infants Born Vaginally or by Cesarean Section. Front Microbiol. 2016;7.Biasucci G, Rubini M, Riboni S, et al. Mode of delivery affects the bacterial community in the newborn gut. Early Hum Dev. 2010;86:13-5.Penders J, Thijs C, Vink C, et al. Factors Influencing the Composition of the Intestinal Microbiota in Early Infancy. Pediatrics. 2006;118:511-21.Negele K, Heinrich J, Borte M, et al. Mode of delivery and development of atopic disease during the first 2 years of life. Pediatr Allergy Immunol. 2004;15:48-54.Guaraldi, F, Salvatori, G. Effect of breast and formula feeding on gut microbiota shaping in newborns. Front Cell Infect Microbiol. 2012;2:94.Williams JE, Price WJ, Shafii B, et al. Relationships among Microbial Communities, Maternal Cells, Oligosaccharides, and Macronutrients in Human Milk. J Hum Lact. 2017;33:540-51.Perez PF, Dore J, Leclerc M, et al. Bacterial Imprinting of the Neonatal Immune System: Lessons from Maternal Cells? Pediatrics. 2007;119:e724-32.Sela DA, Chapman J, Adeuya A, et al. The genome sequence of Bifidobacterium longum subsp. infantis reveals adaptations for milk utilization within the infant microbiome. Proc Natl Acad Sci U S A. 2008;105:18964-9.Stark PL, Lee A. The Microbial Ecology of the Large Bowel of Breastfed and Formula-fed Infants during the First Year of Life. J Med Microbiol. 1982;15:189-203.Chu S, Yu H, Chen Y, et al. Periconceptional and gestational exposure to antibiotics and childhood asthma. PLoS ONE. 2015;10:e0140443.Azad MB, Bridgman SL, Becker AB, Kozyrskyj AL. Infant antibiotic exposure and the development of childhood overweight and central adiposity. Int J Obes. 2014;38:1290-8.Hviid A, Svanstrom H, Frisch M. Antibiotic use and inflammatory bowel diseases in childhood. Gut. 2011;60:49-54.Metsala J, Lundqvist A, Virta LJ, et al. Mother's and offspring's use of antibiotics and infant allergy to cow's milk. Epidemiology. 2013;24:303-9.Bokulich NA, Chung J, Battaglia T, et al. Antibiotics, birth mode, and diet shape microbiome maturation during early life. Sci Transl Med. 2016;8:343-2.Aversa Z, Atkinson EJ, Schafer MJ, et al. Association of infant antibiotic exposure with childhood health outcomes. Mayo Clinic Proc. 2021;96(1):66-77.Turvey SE, Subbarao P. Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: A prospective cohort study. Int J Obstet Gynaecol. 2016;123:983-93.Rakoff-Naboum S, Paglimo J, Eslami-Varzanch F, et al. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004;118:229-41.Ng SC, Hart AL, Kamm MA, et al. Mechanisms of action of probiotics: recent advances. Inflamm. Bowel Dis. 2009;15(2):301-12.Yan F, Polk DB. Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial cells. J Biol Chem. 2002;277:50959-65.Righy R, Kamm MA, Knight SC, et al. Pathogenic bacteria stimulate colonic dendritic cells to produce pro-inflammatory IL-12 while the response to probiotic bacteria is to produce anti-inflammatory IL-10. Gut. 2002;50:A70.Smits HH, Engering A, van Der KD, et al. Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J Allergy Clin Immunol. 2005;115:1260-7.Houghteling PD, Walker WA. Why is initial bsterial colonization of the intestine important to infants’ and children’s health. J Pediatr Gasteroenterol Nutr. 2015;60(3):294-307.Fang H, Elina T, Heikki A, et al. Modulation of humoral immune response through probiotic intake. Immunol Med Microbiol. 2000;29:47-52.Kalliomaki M, Isolauri E. Role of intestinal flora in the development of allergy. Curr Opin All Clin Immunol. 2003;3(1):15-20.Rosenfeldt V, Benfeldt E, Nielsen SD, et al. Effect of probiotic Lactobacillus strains in children with atopic dermatitis. J Allergy Clin Immunol. 2003;111:389-95.Brouwer ML, Wolt-Plompen SA, Dubois AE, et al. No effects of probiotics on atopic dermatitis in infancy: a randomized placebo-controlled trial. Clin Exp Allergy. 2006;36:899-906.Dotterud CK, Avershina E, Sekelja M, et al. Does Maternal Perinatal Probiotic Supplementation Alter the Intestinal Microbiota of Mother and Child? J Pediatr Gastroenterol Nutr. 2015;61:200-7.Murphy R, Morgan X, Wang X, et al. Eczema-protective probiotic alters infant gut microbiome functional capacity but not composition: Sub-sample analysis from a RCT. Benef Microbes. 2019;10:5-17.Rutten NBMM, Gorissen DMW, Eck A, et al. Long Term Development of Gut Microbiota Composition in Atopic Children: Impact of Probiotics. PLoS ONE. 2015;10:e0137681.Abrahamsson TR, Sinkiewicz G, Jakobsson T, et al. Probiotic Lactobacilli in Breast Milk and Infant Stool in Relation to Oral Intake during the First Year of Life. J Pediatr Gastroenterol Nutr. 2009;49:349-54.Fernández L, Cárdenas N, Arroyo R, et al. Prevention of Infectious Mastitis by Oral Administration of Lactobacillus salivarius PS2 During Late Pregnancy. Clin Infect Dis. 2016;62:568-73.Jiménez E, Fernández L, Maldonado A, et al. Oral Administration of Lactobacillus strains isolated from breast milk as an alternative for the treatment of infectious mastitis during lactation. Appl Environ Microbiol. 2008;74:4650-5.Hurtado JA, Maldonado-Lobón JA, Díaz-Ropero MP, et al. Oral administration to nursing women of Lactobacillus fermentum CECT5716 prevents lactational mastitis development: A randomized controlled trial. Breastfeed Med. 2017;12:202-9.Baldassarre ME, Cacciotti F, Miccheli A, et al. Co28 Vsl#3 Probiotic maternal supplementation affects breast milk composition and newborn faeces microbiota. Dig Liver Dis. 2012;44:S253.Zaidi AZ, Moore SE, Okala SG. Impact of Maternal Nutritional Supplementation during Pregnancy and Lactation on the Infant Gut or Breastmilk Microbiota: A Systematic Review. Nutrients. 2021;13:1137. DOI:10.3390/nu13041137Schmidt RM, Laursen RP, Bruun S, et al. Probiotics in late infancy reduce the incidence of eczema. A randomized controlled trial. Pediatr Allergy Immunol. 2019;00:1-6.