Introduction: The early-life intestinal microbiome plays an important role in the development and regulation of the immune system. It is unknown whether the administration of vaccines influences the composition of the intestinal microbiome.

Objective: To investigate whether Bacille Calmette-Guérin (BCG) vaccine given in the first few days of life influences the abundance of bacterial taxa and metabolic pathways in the intestinal microbiome at 1 week of age.

Methods: Healthy, term-born neonates were randomized at birth to receive BCG or no vaccine within the first few days of life. Stool samples were collected at 1 week of age from 335 neonates and analyzed using shotgun metagenomic sequencing and functional analyses.

Results: The composition of the intestinal microbiome was different between neonates born by cesarean section (CS) and those born vaginally. Differences in the composition between BCG-vaccinated and BCG-naïve neonates were only minimal. CS-born BCG-vaccinated neonates had a higher abundance of Staphylococcus lugdunensis compared with CS-born BCG-naïve neonates. The latter had a higher abundance of Streptococcus infantis and Trabulsiella guamensis. Vaginally-born BCG-vaccinated neonates had a higher abundance of Clostridiaceae and Streptococcus parasanguinis compared with vaginally-born BCG-naïve neonates, and a lower abundance of Veillonella atypica and Butyricimonas faecalis. Metabolic pathways that were differently abundant between BCG-vaccinated and BCG-naïve neonates were mainly those involved in sugar degradation and nucleotide/nucleoside biosynthesis.

Conclusion: BCG given in the first few days of life has little effect on the composition of the intestinal microbiome at 1 week of age but does influence the abundance of certain metabolic pathways.