The establishment of the gut microbiota during infancy is one of the most critical processes influencing human health across the lifespan.
Early microbial colonization is deeply intertwined with immune system development, shaping immune tolerance, pathogen resistance, and metabolic processes.
The type of birth, feeding method, environmental exposures, and antibiotic use all play pivotal roles in determining microbial composition (Adamczak et al., 2024; Selma-Royo et al., 2020). These early-life factors not only influence the initial establishment of the microbiota but also have lasting implications for health, as disruptions in microbial colonization have been linked to a range conditions, including allergies, asthma, obesity, and autoimmune conditions (Sarkar et al., 2021).
Infants delivered vaginally acquire microbial communities resembling their mother’s vaginal and intestinal microbiota, rich in Lactobacillus and Bifidobacterium species. In contrast, cesarean-delivered infants harbor more skin-associated microbes and exhibit delayed colonization by beneficial bacteria (Zhang et al., 2022; Selma-Royo et al., 2020).
This divergence is clinically relevant: cesarean delivery has been associated with increased risk for allergic diseases, asthma, and even type 1 diabetes, likely due to altered immune education during the neonatal period (Adamczak et al., 2024).
Breast milk contains a multitude of microbiota-shaping agents including HMOs, immunoglobulins (especially sIgA), and antimicrobial proteins like lactoferrin and lysozyme. These components encourage the proliferation of beneficial microbes, particularly Bifidobacteria, which ferment HMOs to produce short-chain fatty acids (SCFAs) that nourish colonocytes and regulate inflammation (Ximénez & Torres, 2017).
Breastfed infants generally show greater microbial diversity and resilience compared to their formula-fed counterparts (Selma-Royo et al., 2020).
Additionally, proteins such as S100A8 and S100A9 have emerged as key regulators in gut microbiota maturation and immune tolerance, particularly by promoting the development of regulatory T cells (Willers et al., 2020).
The gut microbiota plays an active role in educating the immune system. Microbial signals influence the differentiation of immune cells, the production of mucosal antibodies like IgA, and the balance between pro-inflammatory and anti-inflammatory responses (Ximénez & Torres, 2017; Zhang et al., 2022).
Antibiotic exposure in early life – whether directly administered to the infant or indirectly via the mother – can significantly disrupt microbial colonization. Stevens et al. (2022) found that early antibiotic exposure skews the immune balance, reducing resistance to respiratory infections such as pneumonia and increasing inflammation in the neonatal lung.
Persistent dysbiosis in infancy is associated with a heightened risk of chronic inflammatory conditions, obesity, and even neurological disorders later in life (Adamczak et al., 2024).
The intimate connection between the gut microbiota and the immune system underscores the importance of nurturing early microbial development.
Mode of birth, feeding practices, and prudent antibiotic use are all critical factors in establishing a healthy microbial foundation.
Future research should aim to personalize interventions, such as targeted probiotics or microbial restoration therapies, to optimize immune outcomes and reduce disease risk across the life course.
References
Adamczak, A., Werblińska, A., Jamka, M., & Walkowiak, J. (2024). Maternal-Foetal/Infant Interactions—Gut Microbiota and Immune Health. Biomedicines, 12. https://doi.org/10.3390/biomedicines12030490
Sarkar, A., Yoo, J. Y., Valeria Ozorio Dutra, S., Morgan, K. H., & Groer, M. (2021). The Association between Early-Life Gut Microbiota and Long-Term Health and Diseases. Journal of clinical medicine, 10(3), 459. https://doi.org/10.3390/jcm10030459
Selma-Royo, M., Calatayud Arroyo, M., García-Mantrana, I., Parra-Llorca, A., Escuriet, R., Martínez-Costa, C., & Collado, M. C. (2020). Perinatal environment shapes microbiota colonization and infant growth: impact on host response and intestinal function. Microbiome, 8(1), 167. https://doi.org/10.1186/s40168-020-00940-8
Stevens, J., Steinmeyer, S., Bonfield, M., Peterson, L., Wang, T., Gray, J., Lewkowich, I., Xu, Y., Du, Y., Guo, M., Wynn, J. L., Zacharias, W., Salomonis, N., Miller, L., Chougnet, C., O’Connor, D. H., & Deshmukh, H. (2022). The balance between protective and pathogenic immune responses to pneumonia in the neonatal lung is enforced by gut microbiota. Science translational medicine, 14(649), eabl3981. https://doi.org/10.1126/scitranslmed.abl3981
Willers, M., Ulas, T., Völlger, L., et al. (2020). S100A8 and S100A9 are Important for Postnatal Development of Gut Microbiota and Immune System in Mice and Infants. Gastroenterology. https://doi.org/10.1053/j.gastro.2020.08.019
Ximénez, C., & Torres, J. (2017). Development of Microbiota in Infants and its Role in Maturation of Gut Mucosa and Immune System. Archives of Medical Research, 48(8), 666–680. https://doi.org/10.1016/j.arcmed.2017.11.007
Zhang, H., Zhang, Z., Liao, Y., et al. (2022). The Complex Link and Disease Between the Gut Microbiome and the Immune System in Infants. Frontiers in Cellular and Infection Microbiology, 12. https://doi.org/10.3389/fcimb.2022.924119