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Page 2 of 20 Linehan et al. Microbiome Res Rep. 2025;4:24 https://dx.doi.org/10.20517/mrr.2024.92

Streptococcus and Veillonella species, between the maternal oral cavity and the infant oral cavity occurs in early life.
Perinatal factors such as vaginal delivery and exclusive breastfeeding were strongly associated with enhanced
microbial richness and diversity in infants.

Conclusions: This study provides information on the relationship between health and delivery factors and the first
establishment of the infant microbiota. These findings could offer valuable guidance to clinicians and mothers in
optimizing the infant microbiota toward health during infancy and later life.

Keywords: Infant microbiome, vertical microbial transmission, maternal microbiota, perinatal factors, meconium

INTRODUCTION
The human microbiome comprises diverse microbial communities across various body sites, including the

[1]
skin, respiratory tract, and gastrointestinal system, significantly influencing host health and disease . The
microbiome acts as a companion from birth to death, and its establishment plays a pivotal role in the
development of the immune and nervous systems . Aberrant development of the infant gut microbiota is
[2,3]
associated with an increased risk of colonization by pathogens, impaired growth, and diseases such as
[4,5]
allergies, asthma, and inflammatory bowel disease . Thus, the formation and development of the infant
gut microbiome are critical for ensuring long-term health.

A crucial topic of study pertaining to the infant microbiome is the exact timing of microbial colonization.
[6]
At present, the initial microbial colonization of humans remains controversial . Some studies suggest the
presence of microorganisms in prenatal environments, such as the placenta and amniotic fluid, while others
attribute such findings to contamination in low-biomass samples . Neonates born at term are not
[6,7]
immunologically naive and are specifically adapted to cope with abrupt exposure to microbial, dietary, and
environmental stimuli . Understanding the onset of colonization is critical for unraveling immune
[8,9]
priming mechanisms and optimizing clinical interventions.

The initial assembly of the infant microbiome is primarily driven by the vertical transfer of microbes from
mother to infant [10-12] . Maternal sources, including the gut, skin, oral cavity, vagina, and breast milk,
contribute to this microbial inheritance [13,14] . The establishment of the infant microbiota is also influenced by
perinatal factors such as delivery mode, gestational age, feeding type, maternal health, and antibiotic
exposure . For example, vaginally delivered infants acquire microbiota from the mother’s birth canal and
[15]
intestine, while cesarean-section (CS) delivery disrupts this transmission, often resulting in reduced
beneficial microbes like Bifidobacterium and Bacteroides and an increased abundance of opportunistic
[16]
pathogens . Infants born vaginally and exclusively breastfed, without antibiotic exposure, are considered to
have the optimal microbial colonization .
[17]
Despite advances in our understanding, gaps remain in pinpointing the timing of colonization, the maternal
sources of microbial transmission, and the impact of perinatal factors on the infant microbiota . This study
[14]
aimed to address three key questions: (1) Is the intrauterine environment sterile, or does microbial
colonization begin in utero? (2) What is the contribution of various maternal microbial sources to the infant
microbiota? (3) How do perinatal factors drive microbial inheritance and selection in early life? To answer
these questions, we focussed on three potential maternal sources of microbial transmission (oral, vaginal,
and placental) to the microbiota of their new-born infant (oral and meconium microbiota) and sought to
investigate the contribution of numerous transmission routes and the impact of numerous perinatal factors
on the initial establishment of the infant gut and oral microbiome.