medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2023-494medsovet-8072Research ArticleНЕОНАТОЛОГИЯNEONATOLOGYМикробиота грудного молока здоровых женщин, проживающих в Российской ФедерацииBreast milk microbiota of healthy women living in the Russian Federationhttps://orcid.org/0000-0002-8998-264XКучинаА. Е.KuchinaA. E.

Кучина Анастасия Евгеньевна, врач-педиатр 125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Anastasiya E. Kuchina, Pediatrician

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

kuchina_doc@mail.ruhttps://orcid.org/0000-0003-4200-4598ЗахароваИ. Н.ZakharovaI. N.

Захарова Ирина Николаевна, д.м.н., профессор, заведующая кафедрой педиатрии имени Г.Н. Сперанского

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Irina N. Zakharova, Dr. Sci. (Med.), Professor, Head of the Department of Pediatrics named after G.N. Speransky

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

kafedra25@yandex.ruhttps://orcid.org/0000-0003-1897-4033ОдинцоваВ. Е.OdintsovaV. E.

Одинцова Вера Евгеньевна, руководитель отдела анализа данных

123423, Москва, ул. Народного Ополчения, д. 34, стр. 1, пом. 1/1 

Vera E. Odintsova, Head of Data Analysis Department

 

vera.odintsova@gmail.comhttps://orcid.org/0000-0003-0090-6980ХолодоваИ. Н.KholodovaI. N.

Холодова Ирина Николаевна, д.м.н., профессор кафедры педиатрии имени Г.Н. Сперанского

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1

Irina N. Kholodova, Dr. Sci. (Med.), Professor of the Department of Pediatrics named after G.N. Speransky

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

chin5@yandex.ruhttps://orcid.org/0009-0005-3450-8253КозловаА. Д.KozlovaA. D.

Козлова Александра Дмитриевна, лаборант- исследователь

123098, Москва, пл. Академика Курчатова, д. 1

Aleksandra D. Kozlova, Laboratory Research Assistant

1, Akademik Kurchatov Square, Moscow, 123098

amiandwho@gmail.comhttps://orcid.org/0000-0001-9512-9277КошкинФ. А.KoshkinF. A.

 Кошкин Филипп Александрович, к.б.н., руководитель отдела по планированию и проведению научно-исследовательских проектов

050022, Алматы, ул. Кашгарская, д. 69

Filipp A. Koshkin, Cand. Sci. (Biol.), Head of the Department for Planning and Implementation of Research Projects

69, Kashgarskaya St., Almaty, 050022

philipkoshkin@gmail.comРоссийская медицинская академия непрерывного профессионального образованияРоссияRussian Medical Academy of Continuous Professional EducationRussian FederationAtlas Biomed Group – ООО «Кномикс»РоссияAtlas Biomed Group – Knomics LLCRussian FederationКурчатовский геномный центр НИЦ «Курчатовский институт»РоссияKurchatov Genome Center of the National Research Centre “Kurchatov Institute”Russian FederationТОО «Геномед»КазахстанGenomed LLPKazakhstan202423022024017–18Copyright © Кучина А.Е., Захарова И.Н., Одинцова В.Е., Холодова И.Н., Козлова А.Д., Кошкин Ф.А., 20242024Кучина А.Е., Захарова И.Н., Одинцова В.Е., Холодова И.Н., Козлова А.Д., Кошкин Ф.А.Kuchina A.E., Zakharova I.N., Odintsova V.E., Kholodova I.N., Kozlova A.D., Koshkin F.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/8072Введение

Введение. Грудное молоко матери – лучшее питание для ребенка и, как ни парадоксально, единственный продукт младенческого рациона, состав которого нам до сих пор не полностью известен. Данная статья посвящена результатам впервые проведенного в Российской Федерации исследования микробиоты грудного молока.

Цель

Цель. Изучить состав микробиоты грудного молока здоровых женщин, проживающих в Российской Федерации, и определить влияние различных факторов на его разнообразие.

Материалы и методы

Материалы и методы. Проведено молекулярно-генетическое исследование 56 образцов молозива и 12 образцов зрелого грудного молока от 56 здоровых доноров методом секвенирования бактериального фрагмента гена 16S рРНК.

Результаты

Результаты. В выборке из 56 образцов молозива были идентифицированы 22 типа и 242 рода бактерий. У здоровых женщин с нормальным индексом массы тела, от физиологически протекаю щей беременности, не принимавших антибиотики, после естественных родов в срок наиболее многочисленными типами бактерий оказались Firmicutes, Proteobacteria, Actinobacteriota, на уровне родов были наиболее распространены Streptococcus, Staphylococcus и Gemella. Статистический анализ влияния национальной принадлежности, возраста, количества детей в семье и длительности госпитализации (PERMANOVA) не показал существенных различий в пропорциях бактерий в молозиве женщин (p > 0,05). Единственный фактор, который оказался значимым, – пол ребенка. У матерей девочек биоразнообразие молозива (индекс Шеннона) выше, чем у матерей мальчиков. Кроме того, микробиота зрелого грудного молока (спустя 1 мес. после родов) отличается более низким альфа-разнообразием по сравнению с молозивом.

Обсуждение

Обсуждение. Проанализировав полученные нами результаты и отчеты зарубежных коллег, мы выявили существенные сходства и отличия, которые, безусловно, объясняются рядом причин, связанных с методологическими и географическими различиями, способом, сроком и даже временем суток сбора образцов грудного молока.

Заключение

Заключение. В целом молозиво здоровых женщин имело достаточно стабильный бактериальный состав, а его богатое биоразнообразие в полной мере демонстрировало высокое качество первого микробного инокулята для кишечника новорожденного. Полученные нами результаты дают полное представление о здоровой микробиоте грудного молока женщин, проживающих в Российской Федерации, и могут использоваться в качестве нормативных показателей, а также для сравнения с аналогичными показателями у женщин других стран.

Introduction

Introduction. Mother’s breast milk is considered to be the best source of infant nutrition and, paradoxical as it may sound, the only product of the infant diet, which composition is still poorly known to us. This article presents the findings of a study on the breast milk microbiota conducted in the Russian Federation for the first time.

Aim

Aim. To study the composition of the breast milk microbiota of healthy women living in the Russian Federation and identify the impact of various factors on its diversity.

Materials and methods

Materials and methods. A molecular genetic study on 56 colostrum samples and 12 mature breast milk samples from 56 healthy donors using a method based on sequencing of bacterial 16S rRNA gene was conducted.

Results

Results. In a batch of 56 colostrum samples, 22 species and 242 genera of bacteria were identified. Firmicutes, Proteobacteria, Actinobacteriota were the most predominant species of bacteria in healthy women with a normal body mass index, from a physiological pregnancy, who did not take antibiotics, after natural delivery at term; Streptococcus, Staphylococcus and Gemella were the most predominant at the level of delivery. Statistical analysis of the impact of nationality, age, number of children in the family and duration of hospitalization (PERMANOVA) showed no significant differences in the proportions of bacteria in the colostrum of women (p > 0.05). The gender of the child was the only factor that turned out to be significant. The biodiversity of colostrum of girl-delivered mothers were higher (Shannon index) than that of boy-delivered mothers. In addition, the mature breast milk microbiota (1 month after delivery) has lower alpha diversity as compared to colostrum.

Discussion

Discussion. The analysis of our results and reports from foreign colleagues showed significant similarities and differences, which, certainly, were explained by a number of reasons related to methodological and geographical differences, the method, timing and even the time of day when breast milk samples were collected.

Conclusion

Conclusion. In general, the colostrum of healthy women had a fairly stable bacterial composition, and its rich biodiversity fully demonstrated high quality of the first microbial inoculum for the newborn intestine. Our results provide valuable insights into the healthy breast milk microbiota in women living in the Russian Federation and can be used as reference ranges, as well as for comparison with similar indicators in women from other countries.

молозивозрелое грудное молокосеквенированиебактериальный составбиоразнообразиеcolostrummature breast milksequencingbacterial compositionbiodiversityАвторы выражают благодарность компании Medela за помощь в проведении исследования.The authors would like to thank the Medela Company for assistance in the study conductingReferencesKim SY, Yi DY. Components of human breast milk: from macronutrient to microbiome and microRNA. Clin Exp Pediatr. 2020;63(8):301–309. https://doi.org/10.3345/cep.2020.00059.Kim SY, Yi DY. Components of human breast milk: from macronutrient to microbiome and microRNA. Clin Exp Pediatr. 2020;63(8):301–309. https://doi.org/10.3345/cep.2020.00059.Garwolińska D, Namieśnik J, Kot-Wasik A, Hewelt-Belka W. Chemistry of Human Breast Milk-A Comprehensive Review of the Composition and Role of Milk Metabolites in Child Development. J Agric Food Chem. 2018;66(45):11881–11896. https://doi.org/10.1021/acs.jafc.8b04031.Garwolińska D, Namieśnik J, Kot-Wasik A, Hewelt-Belka W. Chemistry of Human Breast Milk-A Comprehensive Review of the Composition and Role of Milk Metabolites in Child Development. J Agric Food Chem. 2018;66(45):11881–11896. https://doi.org/10.1021/acs.jafc.8b04031.Galante L, Milan AM, Reynolds CM, Cameron-S mith D, Vickers MH, Pundir S. Sex-Specific Human Milk Composition: The Role of Infant Sex in Determining Early Life Nutrition. Nutrients. 2018;10(9):1194. https://doi.org/10.3390/nu10091194.Galante L, Milan AM, Reynolds CM, Cameron-S mith D, Vickers MH, Pundir S. Sex-Specific Human Milk Composition: The Role of Infant Sex in Determining Early Life Nutrition. Nutrients. 2018;10(9):1194. https://doi.org/10.3390/nu10091194.Hahn WH, Song JH, Song S, Kang NM. Do gender and birth height of infant affect calorie of human milk? An association study between human milk macronutrient and various birth factors. J Matern Fetal Neonatal Med. 2017;30(13):1608–1612. https://doi.org/10.1080/14767058.2016.1219989.Hahn WH, Song JH, Song S, Kang NM. Do gender and birth height of infant affect calorie of human milk? An association study between human milk macronutrient and various birth factors. J Matern Fetal Neonatal Med. 2017;30(13):1608–1612. https://doi.org/10.1080/14767058.2016.1219989.Powe CE, Knott CD, Conklin-Brittain N. Infant sex predicts breast milk energy content. Am J Hum Biol. 2010;22(1):50–54. https://doi.org/10.1002/ajhb.20941.Powe CE, Knott CD, Conklin-Brittain N. Infant sex predicts breast milk energy content. Am J Hum Biol. 2010;22(1):50–54. https://doi.org/10.1002/ajhb.20941.Bzikowska-Jura A, Sobieraj P, Szostak-Węgierek D, Wesołowska A. Impact of Infant and Maternal Factors on Energy and Macronutrient Composition of Human Milk. Nutrients. 2020;12(9):2591. https://doi.org/10.3390/nu12092591.Bzikowska-Jura A, Sobieraj P, Szostak-Węgierek D, Wesołowska A. Impact of Infant and Maternal Factors on Energy and Macronutrient Composition of Human Milk. Nutrients. 2020;12(9):2591. https://doi.org/10.3390/nu12092591.Pundir S, Wall CR, Mitchell CJ, Thorstensen EB, Lai CT, Geddes DT, Cameron-Smith D. Variation of Human Milk Glucocorticoids over 24 hour Period. J Mammary Gland Biol Neoplasia. 2017;22(1):85–92. https://doi.org/10.1007/s10911-017-9375-x.Pundir S, Wall CR, Mitchell CJ, Thorstensen EB, Lai CT, Geddes DT, Cameron-Smith D. Variation of Human Milk Glucocorticoids over 24 hour Period. J Mammary Gland Biol Neoplasia. 2017;22(1):85–92. https://doi.org/10.1007/s10911-017-9375-x.Jiang J, Wu K, Yu Z, Ren Y, Zhao Y, Jiang Y et al. Changes in fatty acid composition of human milk over lactation stages and relationship with dietary intake in Chinese women. Food Funct. 2016;7(7):3154–3162. https://doi.org/10.1039/c6fo00304d.Jiang J, Wu K, Yu Z, Ren Y, Zhao Y, Jiang Y et al. Changes in fatty acid composition of human milk over lactation stages and relationship with dietary intake in Chinese women. Food Funct. 2016;7(7):3154–3162. https://doi.org/10.1039/c6fo00304d.Van Sadelhoff JHJ, van de Heijning BJM, Stahl B, Amodio S, Rings EHHM, Mearin ML et al. Longitudinal Variation of Amino Acid Levels in Human Milk and Their Associations with Infant Gender. Nutrients. 2018;10(9):1233. https://doi.org/10.3390/nu10091233.Van Sadelhoff JHJ, van de Heijning BJM, Stahl B, Amodio S, Rings EHHM, Mearin ML et al. Longitudinal Variation of Amino Acid Levels in Human Milk and Their Associations with Infant Gender. Nutrients. 2018;10(9):1233. https://doi.org/10.3390/nu10091233.Martín R, Langa S, Reviriego C, Jimínez E, Marín ML, Xaus J et al. Human milk is a source of lactic acid bacteria for the infant gut. J Pediatr. 2003;143(6):754–758. https://doi.org/10.1016/j.jpeds.2003.09.028.Martín R, Langa S, Reviriego C, Jimínez E, Marín ML, Xaus J et al. Human milk is a source of lactic acid bacteria for the infant gut. J Pediatr. 2003;143(6):754–758. https://doi.org/10.1016/j.jpeds.2003.09.028.Rodríguez JM, Fernández L, Verhasselt V. The Gut – Breast Axis: Programming Health for Life. Nutrients. 2021;13(2):606. https://doi.org/10.3390/nu13020606.Rodríguez JM, Fernández L, Verhasselt V. The Gut – Breast Axis: Programming Health for Life. Nutrients. 2021;13(2):606. https://doi.org/10.3390/nu13020606.Zimmermann P, Curtis N. Breast milk microbiota: A review of the factors that influence composition. J Infect. 2020;81(1):17–47. https://doi.org/10.1016/j.jinf.2020.01.023.Zimmermann P, Curtis N. Breast milk microbiota: A review of the factors that influence composition. J Infect. 2020;81(1):17–47. https://doi.org/10.1016/j.jinf.2020.01.023.Selma-Royo M, Calvo Lerma J, Cortés-Macías E, Collado MC. Human milk microbiome: From actual knowledge to future perspective. Semin Perinatol. 2021;45(6):151450. https://doi.org/10.1016/j.semperi.2021.151450.Selma-Royo M, Calvo Lerma J, Cortés-Macías E, Collado MC. Human milk microbiome: From actual knowledge to future perspective. Semin Perinatol. 2021;45(6):151450. https://doi.org/10.1016/j.semperi.2021.151450.Togo A, Dufour JC, Lagier JC, Dubourg G, Raoult D, Million M. Repertoire of human breast and milk microbiota: a systematic review. Future Microbiol. 2019;14(7):623–641. https://doi.org/10.2217/fmb-2018-0317.Togo A, Dufour JC, Lagier JC, Dubourg G, Raoult D, Million M. Repertoire of human breast and milk microbiota: a systematic review. Future Microbiol. 2019;14(7):623–641. https://doi.org/10.2217/fmb-2018-0317.Efimova D, Tyakht A, Popenko A, Vasilyev A, Altukhov I, Dovidchenko N et al. Knomics-Biota – a system for exploratory analysis of human gut microbiota data. BioData Min. 2018;11:25. https://doi.org/10.1186/s13040018-0187-3.Efimova D, Tyakht A, Popenko A, Vasilyev A, Altukhov I, Dovidchenko N et al. Knomics-Biota – a system for exploratory analysis of human gut microbiota data. BioData Min. 2018;11:25. https://doi.org/10.1186/s13040018-0187-3.Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet CC, Al-Ghalith GA et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol. 2019;37(8):852–857. https://doi.org/10.1038/s41587-019-0209-9.Bolyen E, Rideout JR, Dillon MR, Bokulich NA, Abnet CC, Al-Ghalith GA et al. Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2. Nat Biotechnol. 2019;37(8):852–857. https://doi.org/10.1038/s41587-019-0209-9.Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13(7):581–583. https://doi.org/10.1038/nmeth.3869.Callahan BJ, McMurdie PJ, Rosen MJ, Han AW, Johnson AJ, Holmes SP. DADA2: High-resolution sample inference from Illumina amplicon data. Nat Methods. 2016;13(7):581–583. https://doi.org/10.1038/nmeth.3869.LeMay-Nedjelski L, Copeland J, Wang PW, Butcher J, Unger S, Stintzi A, O’Connor DL. Methods and Strategies to Examine the Human Breastmilk Microbiome. In: Beiko R, Hsiao W, Parkinson J (eds.). Microbiome Analysis. Methods in Molecular Biology. Vol. 1849. New York: Humana Press; 2018, pp. 63–86. https://doi.org/10.1007/978-1-4939-8728-3_5.LeMay-Nedjelski L, Copeland J, Wang PW, Butcher J, Unger S, Stintzi A, O’Connor DL. Methods and Strategies to Examine the Human Breastmilk Microbiome. In: Beiko R, Hsiao W, Parkinson J (eds.). Microbiome Analysis. Methods in Molecular Biology. Vol. 1849. New York: Humana Press; 2018, pp. 63–86. https://doi.org/10.1007/978-1-4939-8728-3_5.Corona-C ervantes K, Zavala-Torres NG, García-Gutiérrez R, Piña-Escobedo A, Hernández-Quiroz F, García-Mena J. Variation of the Human Milk Bacterial Diversity during the Time of the Day. Proceedings. 2020;66(1):33. https://doi.org/10.3390/proceedings2020066033.Corona-C ervantes K, Zavala-Torres NG, García-Gutiérrez R, Piña-Escobedo A, Hernández-Quiroz F, García-Mena J. Variation of the Human Milk Bacterial Diversity during the Time of the Day. Proceedings. 2020;66(1):33. https://doi.org/10.3390/proceedings2020066033.Fitzstevens JL, Smith KC, Hagadorn JI, Caimano MJ, Matson AP, Brownell EA. Systematic Review of the Human Milk Microbiota. Nutr Clin Pract. 2017;32(3):354–364. https://doi.org/10.1177/0884533616670150.Fitzstevens JL, Smith KC, Hagadorn JI, Caimano MJ, Matson AP, Brownell EA. Systematic Review of the Human Milk Microbiota. Nutr Clin Pract. 2017;32(3):354–364. https://doi.org/10.1177/0884533616670150.Jiménez E, de Andrés J, Manrique M, Pareja-Tobes P, Tobes R, Martínez-Blanch JF et al. Metagenomic Analysis of Milk of Healthy and Mastitis-Suffering Women. J Hum Lact. 2015;31(3):406–415. https://doi.org/10.1177/0890334415585078.Jiménez E, de Andrés J, Manrique M, Pareja-Tobes P, Tobes R, Martínez-Blanch JF et al. Metagenomic Analysis of Milk of Healthy and Mastitis-Suffering Women. J Hum Lact. 2015;31(3):406–415. https://doi.org/10.1177/0890334415585078.Boix-Amorós A, Collado MC, Mira A. Relationship between Milk Microbiota, Bacterial Load, Macronutrients, and Human Cells during Lactation. Front Microbiol. 2016;7:492. https://doi.org/10.3389/fmicb.2016.00492.Boix-Amorós A, Collado MC, Mira A. Relationship between Milk Microbiota, Bacterial Load, Macronutrients, and Human Cells during Lactation. Front Microbiol. 2016;7:492. https://doi.org/10.3389/fmicb.2016.00492.Ward TL, Hosid S, Ioshikhes I, Altosaar I. Human milk metagenome: a functional capacity analysis. BMC Microbiol. 2013;13:116. https://doi.org/10.1186/1471-2180-13-116.Ward TL, Hosid S, Ioshikhes I, Altosaar I. Human milk metagenome: a functional capacity analysis. BMC Microbiol. 2013;13:116. https://doi.org/10.1186/1471-2180-13-116.Patel SH, Vaidya YH, Patel RJ, Pandit RJ, Joshi CG, Kunjadiya AP. Culture independent assessment of human milk microbial community in lactational mastitis. Sci Rep. 2017;7(1):7804. https://doi.org/10.1038/s41598017-08451-7.Patel SH, Vaidya YH, Patel RJ, Pandit RJ, Joshi CG, Kunjadiya AP. Culture independent assessment of human milk microbial community in lactational mastitis. Sci Rep. 2017;7(1):7804. https://doi.org/10.1038/s41598017-08451-7.Hermansson H, Kumar H, Collado MC, Salminen S, Isolauri E, Rautava S. Breast Milk Microbiota Is Shaped by Mode of Delivery and Intrapartum Antibiotic Exposure. Front Nutr. 2019;6:4. https://doi.org/10.3389/fnut.2019.00004.Hermansson H, Kumar H, Collado MC, Salminen S, Isolauri E, Rautava S. Breast Milk Microbiota Is Shaped by Mode of Delivery and Intrapartum Antibiotic Exposure. Front Nutr. 2019;6:4. https://doi.org/10.3389/fnut.2019.00004.Jost T, Lacroix C, Braegger C, Chassard C. Assessment of bacterial diversity in breast milk using culture-dependent and culture-independent approaches. Br J Nutr. 2013;110(7):1253–1262. https://doi.org/10.1017/S0007114513000597.Jost T, Lacroix C, Braegger C, Chassard C. Assessment of bacterial diversity in breast milk using culture-dependent and culture-independent approaches. Br J Nutr. 2013;110(7):1253–1262. https://doi.org/10.1017/S0007114513000597.Cabrera-Rubio R, Collado MC, Laitinen K, Salminen S, Isolauri E, Mira A. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr. 2012;96(3):544–551. https://doi.org/10.3945/ajcn.112.037382.Cabrera-Rubio R, Collado MC, Laitinen K, Salminen S, Isolauri E, Mira A. The human milk microbiome changes over lactation and is shaped by maternal weight and mode of delivery. Am J Clin Nutr. 2012;96(3):544–551. https://doi.org/10.3945/ajcn.112.037382.Williams JE, Carrothers JM, Lackey KA, Beatty NF, York MA, Brooker SL et al. Human Milk Microbial Community Structure Is Relatively Stable and Related to Variations in Macronutrient and Micronutrient Intakes in Healthy Lactating Women. J Nutr. 2017;147(9):1739–1748. https://doi.org/10.3945/jn.117.248864.Williams JE, Carrothers JM, Lackey KA, Beatty NF, York MA, Brooker SL et al. Human Milk Microbial Community Structure Is Relatively Stable and Related to Variations in Macronutrient and Micronutrient Intakes in Healthy Lactating Women. J Nutr. 2017;147(9):1739–1748. https://doi.org/10.3945/jn.117.248864.Simpson MR, Avershina E, Storrø O, Johnsen R, Rudi K, Øien T. Breastfeeding-associated microbiota in human milk following supplementation with Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5, and Bifidobacterium animalis ssp. lactis Bb-12. J Dairy Sci. 2018;101(2):889–899. https://doi.org/10.3168/jds.2017-13411.Simpson MR, Avershina E, Storrø O, Johnsen R, Rudi K, Øien T. Breastfeeding-associated microbiota in human milk following supplementation with Lactobacillus rhamnosus GG, Lactobacillus acidophilus La-5, and Bifidobacterium animalis ssp. lactis Bb-12. J Dairy Sci. 2018;101(2):889–899. https://doi.org/10.3168/jds.2017-13411.Tuominen H, Rautava S, Collado MC, Syrjänen S, Rautava J. HPV infection and bacterial microbiota in breast milk and infant oral mucosa. PLoS ONE. 2018;13(11):e0207016. https://doi.org/10.1371/journal.pone.0207016.Tuominen H, Rautava S, Collado MC, Syrjänen S, Rautava J. HPV infection and bacterial microbiota in breast milk and infant oral mucosa. PLoS ONE. 2018;13(11):e0207016. https://doi.org/10.1371/journal.pone.0207016.Drell T, Štšepetova J, Simm J, Rull K, Aleksejeva A, Antson A et al. The Influence of Different Maternal Microbial Communities on the Development of Infant Gut and Oral Microbiota. Sci Rep. 2017;7(1):9940. https://doi.org/10.1038/s41598-017-09278-y.Drell T, Štšepetova J, Simm J, Rull K, Aleksejeva A, Antson A et al. The Influence of Different Maternal Microbial Communities on the Development of Infant Gut and Oral Microbiota. Sci Rep. 2017;7(1):9940. https://doi.org/10.1038/s41598-017-09278-y.Biagi E, Quercia S, Aceti A, Beghetti I, Rampelli S, Turroni S et al. The Bacterial Ecosystem of Mother’s Milk and Infant’s Mouth and Gut. Front Microbiol. 2017;8:1214. https://doi.org/10.3389/fmicb.2017.01214.Biagi E, Quercia S, Aceti A, Beghetti I, Rampelli S, Turroni S et al. The Bacterial Ecosystem of Mother’s Milk and Infant’s Mouth and Gut. Front Microbiol. 2017;8:1214. https://doi.org/10.3389/fmicb.2017.01214.Hendricks-Muñoz KD, Xu J, Parikh HI, Xu P, Fettweis JM, Kim Y et al. Skin-to-Skin Care and the Development of the Preterm Infant Oral Microbiome. Am J Perinatol. 2015;32(13):1205–1216. https://doi.org/10.1055/s-0035-1552941.Hendricks-Muñoz KD, Xu J, Parikh HI, Xu P, Fettweis JM, Kim Y et al. Skin-to-Skin Care and the Development of the Preterm Infant Oral Microbiome. Am J Perinatol. 2015;32(13):1205–1216. https://doi.org/10.1055/s-0035-1552941.Zaura E, Nicu EA, Krom BP, Keijser BJ. Acquiring and maintaining a normal oral microbiome: current perspective. Front Cell Infect Microbiol. 2014;4:85. https://doi.org/10.3389/fcimb.2014.00085.Zaura E, Nicu EA, Krom BP, Keijser BJ. Acquiring and maintaining a normal oral microbiome: current perspective. Front Cell Infect Microbiol. 2014;4:85. https://doi.org/10.3389/fcimb.2014.00085.Li K, Bihan M, Methé BA. Analyses of the stability and core taxonomic memberships of the human microbiome. PLoS ONE. 2013;8(5):e63139. https://doi.org/10.1371/journal.pone.0063139.Li K, Bihan M, Methé BA. Analyses of the stability and core taxonomic memberships of the human microbiome. PLoS ONE. 2013;8(5):e63139. https://doi.org/10.1371/journal.pone.0063139.Родригеc ХМ. Микробиота женского молока. Consilium Medicum. Педиатрия (Прил.). 2016;(4):35–40. Режим доступа: https://omnidoctor.ru/library/izdaniya-dlya-vrachey/pediatriya-consilium-medicum/ped2016/ped2016_4/mikrobiota-zhenskogo-moloka/.Rodríguez JM. The human milk microbiota. Consilium Medicum. Pediatrics (Suppl.). 2016;(4):35–40. (In Russ.) Available at: https://omnidoctor.ru/library/izdaniya-dlya-vrachey/pediatriya-consilium-medicum/ped2016/ped2016_4/mikrobiota-zhenskogo-moloka/.Ramsay DT, Kent JC, Owens RA, Hartmann PE. Ultrasound imaging of milk ejection in the breast of lactating women. Pediatrics. 2004;113(2):361–367. https://doi.org/10.1542/peds.113.2.361.Ramsay DT, Kent JC, Owens RA, Hartmann PE. Ultrasound imaging of milk ejection in the breast of lactating women. Pediatrics. 2004;113(2):361–367. https://doi.org/10.1542/peds.113.2.361.Taylor R, Keane D, Borrego P, Arcaro K. Effect of Maternal Diet on Maternal Milk and Breastfed Infant Gut Microbiomes: A Scoping Review. Nutrients. 2023;15(6):1420. https://doi.org/10.3390/nu15061420.Taylor R, Keane D, Borrego P, Arcaro K. Effect of Maternal Diet on Maternal Milk and Breastfed Infant Gut Microbiomes: A Scoping Review. Nutrients. 2023;15(6):1420. https://doi.org/10.3390/nu15061420.Taghizadeh M, Mirlohi M, Poursina F, Madani G, Khoshhali M, Bahreini N, Safaei HG. The influence of impact delivery mode, lactation time, infant gender, maternal age and rural or urban life on total number of Lactobacillus in breast milk Isfahan – Iran. Adv Biomed Res. 2015;4(1):141. https://doi.org/10.4103/2277-9175.161546.Taghizadeh M, Mirlohi M, Poursina F, Madani G, Khoshhali M, Bahreini N, Safaei HG. The influence of impact delivery mode, lactation time, infant gender, maternal age and rural or urban life on total number of Lactobacillus in breast milk Isfahan – Iran. Adv Biomed Res. 2015;4(1):141. https://doi.org/10.4103/2277-9175.161546.Vaidya YH, Patel SH, Patel RJ, Pandit RJ, Joshi CG, Kunjadia AP. Human milk microbiome in urban and rural populations of India. Meta Gene. 2017;13:13–22. https://doi.org/10.1016/j.mgene.2017.04.001.Vaidya YH, Patel SH, Patel RJ, Pandit RJ, Joshi CG, Kunjadia AP. Human milk microbiome in urban and rural populations of India. Meta Gene. 2017;13:13–22. https://doi.org/10.1016/j.mgene.2017.04.001.Kumar H, du Toit E, Kulkarni A, Aakko J, Linderborg KM, Zhang Y et al. Distinct Patterns in Human Milk Microbiota and Fatty Acid Profiles Across Specific Geographic Locations. Front Microbiol. 2016;7:1619. https://doi.org/10.3389/fmicb.2016.01619.Kumar H, du Toit E, Kulkarni A, Aakko J, Linderborg KM, Zhang Y et al. Distinct Patterns in Human Milk Microbiota and Fatty Acid Profiles Across Specific Geographic Locations. Front Microbiol. 2016;7:1619. https://doi.org/10.3389/fmicb.2016.01619.Moossavi S, Sepehri S, Robertson B, Bode L, Goruk S, Field CJ et al. Composition and Variation of the Human Milk Microbiota Are Influenced by Maternal and Early-Life Factors. Cell Host Microbe. 2019;25(2):324–335. e4. https://doi.org/10.1016/j.chom.2019.01.011.Moossavi S, Sepehri S, Robertson B, Bode L, Goruk S, Field CJ et al. Composition and Variation of the Human Milk Microbiota Are Influenced by Maternal and Early-Life Factors. Cell Host Microbe. 2019;25(2):324–335. e4. https://doi.org/10.1016/j.chom.2019.01.011.Pannaraj PS, Li F, Cerini C, Bender JM, Yang S, Rollie A et al. Association Between Breast Milk Bacterial Communities and Establishment and Development of the Infant Gut Microbiome. JAMA Pediatr. 2017;171(7):647–654. https://doi.org/10.1001/jamapediatrics.2017.0378.Pannaraj PS, Li F, Cerini C, Bender JM, Yang S, Rollie A et al. Association Between Breast Milk Bacterial Communities and Establishment and Development of the Infant Gut Microbiome. JAMA Pediatr. 2017;171(7):647–654. https://doi.org/10.1001/jamapediatrics.2017.0378.Markle JG, Frank DN, Mortin-Toth S, Robertson CE, Feazel LM, Rolle-Kampczyk U et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science. 2013;339(6123):1084–1088. https://doi.org/10.1126/science.1233521.Markle JG, Frank DN, Mortin-Toth S, Robertson CE, Feazel LM, Rolle-Kampczyk U et al. Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity. Science. 2013;339(6123):1084–1088. https://doi.org/10.1126/science.1233521.Santos-Marcos JA, Mora-Ortiz M, Tena-Sempere M, Lopez-Miranda J, Camargo A. Interaction between gut microbiota and sex hormones and their relation to sexual dimorphism in metabolic diseases. Biol Sex Differ. 2023;14(1):4. https://doi.org/10.1186/s13293-023-00490-2.Santos-Marcos JA, Mora-Ortiz M, Tena-Sempere M, Lopez-Miranda J, Camargo A. Interaction between gut microbiota and sex hormones and their relation to sexual dimorphism in metabolic diseases. Biol Sex Differ. 2023;14(1):4. https://doi.org/10.1186/s13293-023-00490-2.Park CH, Lee EJ, Kim HL, Lee YT, Yoon KJ, Kim HN. Sex-specific associations between gut microbiota and skeletal muscle mass in a population-b ased study. J Cachexia Sarcopenia Muscle. 2022;13(6):2908–2919. https://doi.org/10.1002/jcsm.13096.Park CH, Lee EJ, Kim HL, Lee YT, Yoon KJ, Kim HN. Sex-specific associations between gut microbiota and skeletal muscle mass in a population-b ased study. J Cachexia Sarcopenia Muscle. 2022;13(6):2908–2919. https://doi.org/10.1002/jcsm.13096.Maffei S, Forini F, Canale P, Nicolini G, Guiducci L. Gut Microbiota and Sex Hormones: Crosstalking Players in Cardiometabolic and Cardiovascular Disease. Int J Mol Sci. 2022;23(13):7154. https://doi.org/10.3390/ijms23137154.Maffei S, Forini F, Canale P, Nicolini G, Guiducci L. Gut Microbiota and Sex Hormones: Crosstalking Players in Cardiometabolic and Cardiovascular Disease. Int J Mol Sci. 2022;23(13):7154. https://doi.org/10.3390/ijms23137154.Ojo-Okunola A, Claassen-Weitz S, Mwaikono KS, Gardner-Lubbe S, Stein DJ, Zar HJ et al. Influence of Socio-Economic and Psychosocial Profiles on the Human Breast Milk Bacteriome of South African Women. Nutrients. 2019;11(6):1390. https://doi.org/10.3390/nu11061390.Ojo-Okunola A, Claassen-Weitz S, Mwaikono KS, Gardner-Lubbe S, Stein DJ, Zar HJ et al. Influence of Socio-Economic and Psychosocial Profiles on the Human Breast Milk Bacteriome of South African Women. Nutrients. 2019;11(6):1390. https://doi.org/10.3390/nu11061390.Rodríguez JM. The origin of human milk bacteria: is there a bacterial entero-mammary pathway during late pregnancy and lactation? Adv Nutr. 2014;5(6):779–784. https://doi.org/10.3945/an.114.007229.Rodríguez JM. The origin of human milk bacteria: is there a bacterial entero-mammary pathway during late pregnancy and lactation? Adv Nutr. 2014;5(6):779–784. https://doi.org/10.3945/an.114.007229.Moossavi S, Sepehri S, Robertson B, Bode L, Goruk S, Field CJ et al. Composition and Variation of the Human Milk Microbiota Are Influenced by Maternal and Early-Life Factors. Cell Host Microbe. 2019;25(2):324–335.e4. https://doi.org/10.1016/j.chom.2019.01.011.Moossavi S, Sepehri S, Robertson B, Bode L, Goruk S, Field CJ et al. Composition and Variation of the Human Milk Microbiota Are Influenced by Maternal and Early-Life Factors. Cell Host Microbe. 2019;25(2):324–335.e4. https://doi.org/10.1016/j.chom.2019.01.011.Penders J, Gerhold K, Stobberingh EE, Thijs C, Zimmermann K, Lau S, Hamelmann E. Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood. J Allergy Clin Immunol. 2013;132(3):601–607.e8. https://doi.org/10.1016/j.jaci.2013.05.043.Penders J, Gerhold K, Stobberingh EE, Thijs C, Zimmermann K, Lau S, Hamelmann E. Establishment of the intestinal microbiota and its role for atopic dermatitis in early childhood. J Allergy Clin Immunol. 2013;132(3):601–607.e8. https://doi.org/10.1016/j.jaci.2013.05.043.Solís G, de Los Reyes-Gavilan CG, Fernández N, Margolles A, Gueimonde M. Establishment and development of lactic acid bacteria and bifidobacteria microbiota in breast-milk and the infant gut. Anaerobe. 2010;16(3):307–310. https://doi.org/10.1016/j.anaerobe.2010.02.004.Solís G, de Los Reyes-Gavilan CG, Fernández N, Margolles A, Gueimonde M. Establishment and development of lactic acid bacteria and bifidobacteria microbiota in breast-milk and the infant gut. Anaerobe. 2010;16(3):307–310. https://doi.org/10.1016/j.anaerobe.2010.02.004.Dominguez-Bello MG, Godoy-Vitorino F, Knight R, Blaser MJ. Role of the microbiome in human development. Gut. 2019;68(6):1108–1114. https://doi.org/10.1136/gutjnl-2018-317503.Dominguez-Bello MG, Godoy-Vitorino F, Knight R, Blaser MJ. Role of the microbiome in human development. Gut. 2019;68(6):1108–1114. https://doi.org/10.1136/gutjnl-2018-317503.Shao Y, Forster SC, Tsaliki E, Vervier K, Strang A, Simpson N et al. Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. Nature. 2019;574(7776):117–121. https://doi.org/10.1038/s41586-019-1560-1.Shao Y, Forster SC, Tsaliki E, Vervier K, Strang A, Simpson N et al. Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth. Nature. 2019;574(7776):117–121. https://doi.org/10.1038/s41586-019-1560-1.Ben Maamar S, Hu J, Hartmann EM. Implications of indoor microbial ecology and evolution on antibiotic resistance. J Expo Sci Environ Epidemiol. 2020;30(1):1–15. https://doi.org/10.1038/s41370-019-0171-0.Ben Maamar S, Hu J, Hartmann EM. Implications of indoor microbial ecology and evolution on antibiotic resistance. J Expo Sci Environ Epidemiol. 2020;30(1):1–15. https://doi.org/10.1038/s41370-019-0171-0.Lax S, Sangwan N, Smith D, Larsen P, Handley KM, Richardson Met al. Bacterial colonization and succession in a newly opened hospital. Sci Transl Med. 2017;9(391):eaah6500. https://doi.org/10.1126/scitranslmed.aah6500.Lax S, Sangwan N, Smith D, Larsen P, Handley KM, Richardson Met al. Bacterial colonization and succession in a newly opened hospital. Sci Transl Med. 2017;9(391):eaah6500. https://doi.org/10.1126/scitranslmed.aah6500.He S, Li H, Yu Z, Zhang F, Liang S, Liu H et al. The Gut Microbiome and Sex Hormone-Related Diseases. Front Microbiol. 2021;12:711137. https://doi.org/10.3389/fmicb.2021.711137.He S, Li H, Yu Z, Zhang F, Liang S, Liu H et al. The Gut Microbiome and Sex Hormone-Related Diseases. Front Microbiol. 2021;12:711137. https://doi.org/10.3389/fmicb.2021.711137.Calcaterra V, Rossi V, Massini G, Regalbuto C, Hruby C, Panelli S et al. Precocious puberty and microbiota: The role of the sex hormone-gut microbiome axis. Front Endocrinol (Lausanne). 2022;13:1000919. https://doi.org/10.3389/fendo.2022.1000919.Calcaterra V, Rossi V, Massini G, Regalbuto C, Hruby C, Panelli S et al. Precocious puberty and microbiota: The role of the sex hormone-gut microbiome axis. Front Endocrinol (Lausanne). 2022;13:1000919. https://doi.org/10.3389/fendo.2022.1000919.Deschasaux M, Bouter KE, Prodan A, Levin E, Groen AK, Herrema H et al. Depicting the composition of gut microbiota in a population with varied ethnic origins but shared geography. Nat Med. 2018;24(10):1526–1531. https://doi.org/10.1038/s41591-018-0160-1.Deschasaux M, Bouter KE, Prodan A, Levin E, Groen AK, Herrema H et al. Depicting the composition of gut microbiota in a population with varied ethnic origins but shared geography. Nat Med. 2018;24(10):1526–1531. https://doi.org/10.1038/s41591-018-0160-1.Захарова ИН, Бережная ИВ, Кучина АЕ, Дедикова ОВ. Пробиотик Lacto bacil lus reuteri DSM 17938: что известно о нем сегодня? Медицинский совет. 2019;(17):236–242. https://doi.org/10.21518/2079-701X-2019-17-236-242.Zakharova IN, Berezhnaya IV, Kuchina AЕ, Dedikova OV. Probiotic Lactobacillus reuteri DSM 17938: what is known about it today? Meditsinskiy Sovet. 2019;(17):236–242. (In Russ.) https://doi.org/10.21518/2079-701X-2019-17-236-242.

The authors declare that there are no conflicts of interest present.