Dynamics of gut microbiota development in healthy term infants during the first month of life
Priputnevich T.V., Denisov P.A., Muravieva V.V., Lyubasovskaya L.A., Isaeva E.L., Shabanova N.E., Bembeeva B.O., Trofimov D.Yu., Balashova E.N., Zubkov V.V., Nikolaeva A.V.
The establishment of the gut microbiota is a crucial developmental stage for infants in the first month of life. The sequential colonization of the gut and initiation of immunological signaling cascades through intestinal receptors represent an evolutionarily determined strategy for postnatal adaptation. Disruptions to this sequence, such as cesarean delivery, formula feeding, or preterm birth, may lead to adaptive disturbances ranging from mild digestive disorders to life-threatening conditions such as necrotizing enterocolitis (NEC) and sepsis. Therefore, comparing the gut microbiota of newborns at different time points is essential for identifying the pathological trends that may precede NEC.
Objective: To assess changes in the composition of the gut microbiota in healthy term infants during the first month of life.
Materials and methods: Gut microbiota samples were collected from term newborns delivered at the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology of the Ministry of Health of the Russian Federation. Samples were obtained at three time points: day 1 of life (meconium), day 7, and day 30 of life. The microbiota composition was analyzed using 16S rRNA gene metagenomic sequencing.
Results: The study revealed significant differences in microbiota composition between the first week of life and day 30, a period critical for NEC development. During the first week, Staphylococcus species predominated, and their relative abundance declined on days 7 and 30. Concurrently, Escherichia coli colonization progressively increased, peaking on day 30, indicating the gradual establishment of this species in the infant gut. The relative abundance of Bifidobacterium species varied significantly across the time points. By the end of the first month, an increase in Bifidobacterium animalis was observed, indicating the onset of probiotic microbiota formation. These findings emphasize the critical role of the early postnatal period in shaping the gut microbiota and its potential impact on the immunological and physiological development of the newborn.
Conclusion: The first days of life are critical for establishing the gut microbiota, characterized by an active transition from facultative anaerobes to obligate anaerobic microorganisms. Timely colonization by Lactobacilli and Bifidobacteria plays an important preventive role against NEC. The observed increase in microbial diversity with postnatal age reflects the gradual formation of a stable gut microbiome.
Authors' contributions: Priputnevich T.V., Zubkov V.V., Nikolaeva A.V. – study supervision; Denisov P.A. – bioinformatic and statistical analysis, visualization, drafting of the manuscript, interpretation; Isaeva E.L., Muravieva V.V., Bembeeva B.O. – preparation of microbiological material, drafting of the manuscript; Shabanova N.E., Lyubasovskaya L.A. – drafting of the manuscript, final approval of the version for submission; Balashova E.N., Zubkov V.V. – data collection; Trofimov D.Yu. – molecular genetic studies, drafting of the manuscript.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: The study was carried out as part of the Ministry of Health of Russia's state task, “Development of an integrated approach to diagnosing and correcting dysbiotic disorders of the intestinal microbiota caused by antibacterial therapy in newborns” (124020600025-2).
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the V.I. Kulakov NMRC for OG&P (Ref. No. 03 of March 21, 2024).
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Priputnevich T.V., Denisov P.A., Muravieva V.V., Lyubasovskaya L.A., Isaeva E.L., Shabanova N.E., Bembeeva B.O., Trofimov D.Yu., Balashova E.N., Zubkov V.V., Nikolaeva A.V. Dynamics of gut microbiota development in healthy term infants during the first month of life.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2026; (1): 45-54 (in Russian)
https://dx.doi.org/10.18565/aig.2025.371
Keywords
gut microbiota
term newborns
probiotics
necrotizing enterocolitis
metagenomic sequencing
References
- Aagaard K., Ma J., Antony K. M., Ganu R., Petrosino J., Versalovic J. The placenta harbors a unique microbiome. Sci. Transl. Med. 2014; 6(237): 237ra65. https://dx.doi.org/10.1126/scitranslmed.3008599
- Odendaal J., Black N., Bennett P.R., Brosens J., Quenby S., MacIntyre D.A. The endometrial microbiota and early pregnancy loss. Hum. Reprod. 2024; 39(4): 638-46. https://dx.doi.org/10.1093/humrep/dead274
- Balla B., Illés A., Tobiás B., Pikó H., Beke A., Sipos M. et al. The role of the vaginal and endometrial microbiomes in infertility and their impact on pregnancy outcomes in light of recent literature. Int. J. Mol. Sci. 2024; 25(23): 13227. https://dx.doi.org/10.3390/ijms252313227
- Moreno I., Franasiak J.M. Endometrial microbiota – new player in town. Fertil. Steril. 2017; 108(1): 32-9. https://dx.doi.org/10.1016/j.fertnstert.2017.05.034
- Ganguli K., Meng D., Rautava S., Lu L., Walker W.A., Nanthakumar N. Probiotics prevent necrotizing enterocolitis by modulating enterocyte genes that regulate innate immune-mediated inflammation. Am. J. Physiol. Gastrointest. Liver Physiol. 2013; 304(2): G132-41. https://dx.doi.org/10.1152/AJPGI.00142.2012
- Gorreja F., Rush S.T.A., Kasper D.L., Meng D., Allan Walker W. The developmentally regulated fetal enterocyte gene, ZP4, mediates antiinflammation by the symbiotic bacterial surface factor polysaccharide a on Bacteroides fragilis. Am. J. Physiol. Gastrointest. Liver Physiol. 2019; 317(4): G398-G407. https://dx.doi.org/10.1152/AJPGI.00046.2019
- Meng D., Zhu W., Shi H.N., Lu L., Wijendran V., Xu W. et al. Toll-like receptor-4 in human and mouse colonic epithelium is developmentally regulated: a possible role in necrotizing enterocolitis. Pediatr. Res. 2015; 77(3), 416-24. https://dx.doi.org/10.1038/PR.2014.207
- ОСТ 91500.11.0004-2003. Отраслевой стандарт. Протокол ведения больных. Дисбактериоз кишечника (утв. Приказом Минздрава России от 09.06.2003 № 231). Доступно по: https://normativ.kontur.ru/document?moduleId=9&documentId=62571 [OST 91500.11.0004-2003. Industry standard. Protocol for managing patients. Intestinal dysbiosis (approved by Order No. 231 of the Russian Ministry of Health dated June 9, 2003). Available at: https://normativ.kontur.ru/document?moduleId=9&documentId=62571(in Russian)].
- Припутневич Т.В., Исаева Е.Л., Муравьева В.В., Месян М.К., Зубков В.В., Николаева А.В., Бембеева Б.О., Тимофеева Л.А., Козлова А.А., Макаров В.В., Юдин С.М. Становление микробиоты кишечника доношенных и поздних недоношенных детей, рожденных самопроизвольно и путем операции кесарева сечения. Неонатология: новости, мнения, обучение. 2023; 11(1): 42-56. [Priputnevich T.V., Isaeva E.L., Muravieva V.V., Mesyan M.K., Zubkov V.V., Nikolaeva A.V., Bembeeva B.O., Timofeeva L.A., Kozlova A.A., Makarov V.V., Yudin S.M. Development of the gut microbiota of term and late preterm newborn infants. Neonatology: news, opinions, training. 2023; 11(1): 42-56 (in Russian)]. https://dx.doi.org/10.33029/2308-2402-2023-11-1-42-56
- Andrews S. FastQC: A quality control tool for high throughput sequence data. 2010. Available at: https://www.bioinformatics.babraham.ac.uk/projects/fastqc/
- Bolger A.M., Lohse M., Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014; 30(15): 2114-20. https://dx.doi.org/10.1093/bioinformatics/btu170
- Wood D.E., Lu J., Langmead B. Improved metagenomic analysis with Kraken 2. Genome Biol. 2019; 20(1): 257. https://dx.doi.org/10.1186/s13059-019-1891-0
- Lu J., Rincon N., Wood D.E., Breitwieser F.P., Pockrandt C., Langmead B. et al. Metagenome analysis using the Kraken software suite. Nature Protocols. 2022; 17(12): 2815-39. https://dx.doi.org/10.1038/s41596-022-00738-y
- Lu J., Breitwieser F.P., Thielen P., Salzberg S.L. Bracken: estimating species abundance in metagenomics data. PeerJ Comput. Sci. 2017; 3: e104. https://dx.doi.org/10.7717/peerj-cs.104
- Oksanen J., Simpson G.L., Blanchet F.G., Kindt R., Legendre P., Minchin P.R. et al. vegan: Community Ecology Package. In: CRAN: Contributed Packages. https://dx.doi.org/10.32614/CRAN.package.vegan
- McMurdie P.J., Holmes S. Phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data. PloS One. 2013; 8(4): e61217. https://dx.doi.org/10.1371/journal.pone.0061217
- Barajas H.R., Romero M.F., Martínez-Sánchez S., Alcaraz L.D. Global genomic similarity and core genome sequence diversity of the Streptococcus genus as a toolkit to identify closely related bacterial species in complex environments. PeerJ. 2019; 6: e6233. https://dx.doi.org/10.7717/peerj.6233
- Walker A.W., Duncan S.H., Louis P., Flint H.J. Phylogeny, culturing, and metagenomics of the human gut microbiota. Trends Microbiol. 2014; 22(5): 267-74. https://dx.doi.org/10.1016/j.tim.2014.03.001
- Bäckhed F., Roswall J., Peng Y., Feng Q., Jia H., Kovatcheva-Datchary P. et al. Dynamics and stabilization of the human gut microbiome during the first year of life. Cell Host Microbe. 2015; 17(5): 690-703. https://dx.doi.org/10.1016/j.chom.2015.04.004
- Korpela K. Impact of delivery mode on infant gut microbiota. Ann. Nutr. Metab. 2021; 77(Suppl. 3): 11-9. https://dx.doi.org/10.1159/000518498
- Ma J., Li Z., Zhang W., Zhang C., Zhang Y., Mei H. et al. Comparison of the gut microbiota in healthy infants with different delivery modes and feeding types: a cohort study. Front. Microbiol. 2022; 13: 868227. https://dx.doi.org/10.3389/fmicb.2022.868227
- Mollitt D.L., Tepas J.J., Talbert J.L. The role of coagulase-negative Staphylococcus in neonatal necrotizing enterocolitis. J. Pediatr. Surg. 1988; 23(1): 60-3. https://dx.doi.org/10.1016/S0022-3468(88)80542-6
- Sáenz De Pipaón Marcos M., Rodríguez Delgado J., Martínez Biarge M., Pérez Rodríguez J., Sosa Rotundo G., Tovar Larrucea J.A. et al. Low mortality in necrotizing enterocolitis associated with coagulase-negative Staphylococcus infection. Pediatr. Surg. Int. 2008; 24(7): 831-5. https://dx.doi.org/10.1007/s00383-008-2168-y
- Patel R.M., Underwood M.A. Probiotics and necrotizing enterocolitis. Semin. Pediatr. Surg. 2018; 27(1): 39-46. https://dx.doi.org/10.1053/j.sempedsurg.2017.11.008
Received 15.12.2025
Accepted 24.12.2025
About the Authors
Tatiana V. Priputnevich, Dr. Med. Sci., Corresponding Members of the RAS, Director of the Institute of Microbiology, Antimicrobial Therapy and Epidemiology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Oparina str., Moscow, 117997, Russia; Professor at the Department of Microbiology named after Academician Z.V. Ermolieva, RMANPO of the Ministry of Health of Russia, t_priputnevich@oparina4.ru,https://orcid.org/0000-0002-4126-9730
Pavel A. Denisov, Researcher at the Laboratory of Bioinformatic Analysis of the Institute of Microbiology, Antimicrobial Therapy and Epidemiology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Oparina str., Moscow, 117997, Russia,
denisov@neuro.nnov.ru, https://orcid.org/0000-0003-1813-6718
Vera V. Muravieva, PhD, Senior Researcher at the Laboratory of Molecular Microbiology of the Institute of Microbiology, Antimicrobial Therapy and Epidemiology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Oparina str., Moscow, 117997, Russia, v_muravieva@oparina4.ru, https://orcid.org/0000-0003-0383-0731
Lyudmila A. Lyubasovskaya, PhD, Clinical Pharmacologist, MMCC Voronovskoye of Moscow Healthcare Department; Associate Professor at the Department of Medical Microbiology named after Academician Z.V. Ermolyeva, RMANPO, Ministry of Health of Russia, labmik@yandex.ru, https://orcid.org/0000-0002-7456-9940
Elena L. Isaeva, PhD, Senior Researcher at the Institute of Microbiology, Antimicrobial Therapy and Epidemiology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Oparina str., Moscow, 117997, Russia, isaeva73@bk.ru, https://orcid.org/0000-0001-6224-8202
Natalya E. Shabanova, PhD, Associate Professor, Head of the Department of Clinical Pharmacology of the Institute of Microbiology, Antimicrobial Therapy and Epidemiology,
Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Oparina str., Moscow,
117997, Russia, n_shabanova@oparina4.ru, https://orcid.org/0000-0001-6838-3616
Bayr O. Bembeeva, Researcher, Institute of Microbiology, Antimicrobial Therapy and Epidemiology, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Oparina str., Moscow, 117997, Russia; Teaching Assistant, Pirogov RNRMU, Ministry of Health of Russia, b_bembeeva@oparina4.ru, https://orcid.org/0000-0002-8820-9903
Dmitry Yu. Trofimov, Dr. Bio. Sci., Director of the Institute of Reproductive Genetics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Oparina str., Moscow, 117997, Russia, d_trofimov@oparina4.ru, https://orcid.org/0000-0002-1569-8486
Ekaterina N. Balashova, PhD, Leading Researcher at the Department of Resuscitation and Intensive Care of Newborns at the Institute of Neonatology and Pediatrics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Oparina str., Moscow,
117997, Russia, e_balashova@oparina4.ru, https://orcid.org/0000-0002-3741-0770
Viktor V. Zubkov, Dr. Med. Sci., Director of the Institute of Neonatology and Pediatrics, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 4, Oparina str., Moscow, 117997, Russia, v_zubkov@oparina4.ru, https://orcid.org/0000-0001-8366-5208
Anastasia V. Nikolaeva, PhD, Chief Physician, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health
of Russia, 4, Oparina str., Moscow, 117997, Russia, a_nikolaeva@oparina4.ru, https://orcid.org/0000-0002-0012-6688
Corresponding author: Pavel A. Denisov, denisov@neuro.nnov.ru
Similar Articles
