Background: Early-life microbial colonisation is believed to play a role in immune programming and later life health, yet the evidence regarding the origins, timing and significance of the neonatal microbiome remains inconclusive due to problematic study design, biased amplification and contamination.
Method: Placental, amniotic fluid, first-pass meconium and cord blood samples were collected from 50 elective Caesarean section deliveries. An optimised sampling and analysis protocol was employed to minimise/control for contamination, allowing characterisation of the fetal gut microbiome and its relationship with maternal parameters, short chain fatty acid (SCFA) levels and inflammation.
Results: All meconium samples contained detectable levels of bacterial DNA and the immunomodulatory SCFAs acetate and propionate, confirming the hypothesis that the fetal gut is inoculated with bacteria/bacterial DNA in utero. At the phylum level, meconium was dominated by Proteobacteria and Firmicutes. Acinetobacter - known to be allergy protective - was the most abundant genus (found in 95% of samples). Importantly, this genus has been found in the core non-pregnant endometrial microbiome, but not paired vaginal samples. Lactobacillus (which dominates the vaginal microbiome) was found in only 5 samples. Presence and abundance of Acinetobacter DNA was associated with elevated immune responses to 5’ppp-dsDNA (a RIG-I agonist). Maternal diabetes, intra-amniotic inflammation and SCFA levels were all associated with altered meconium microbiome.
Conclusions: Seeding of the fetal gut microbiome commences prenatally and may originate from the endometrial microbiome present at time of conception; vaginal contribution appears minimal. Maternal metabolic health and intrauterine inflammation may influence fetal immune programming via modulation of the fetal microbiome and immunomodulatory SCFAs.