Denise Al Alam, Soula Danopoulos, Matthew Thornton, Brendan Grubbs, David Warburton, Timothy Wang, Namasivayam Ambalavanan, Charitharth Vivek Lal
The myth of the sterile fetus has been challenged by several recent studies showing evidence of microbial DNA, microbial products, and occasionally living bacteria within the placenta and amniotic fluid. Moreover, recent studies have confirmed the presence of a diverse microbiome in the human lung, including neonates, but the origin of the microbiome remains elusive. Herein, we aimed to investigate the presence and origin of a human fetal lung microbiome. Eighteen de-identified human fetal lung tissues from 11 weeks gestation (1st trimester) to 20 weeks gestation (2nd trimester), along with 10 matched placentas, were collected following sterile and standardized clinical procedures. Samples were processed and microbiome analysis was conducted on each sample. Bacterial DNA was detected and characterized in all fetal lung and placenta samples. Principal coordinates analysis (PCoA) plot analysis of the human fetal lung microbiomes split into two separate groups (11-15 week gestation versus 16-20 week gestation) demonstrated increasing beta diversity. Our analysis of the distance and clustering of the samples (closer clustering signifying shared larger proportion of phylogenetic tree) showed that there was a significant change in the microbiome diversity between the two gestational groups. This suggests that the lung microbiome diversity changes as gestational age of the human fetus increases. To compare the microbiota of fetal lung and placenta, we analyzed 10 'matched pair' sets. Overall analysis of the bacterial taxa distribution and diversity showed striking similarity in the microbiota of matched lungs and placentas. These results show that the fetal lung microbiome is extremely similar to the placental microbiome in matched pairs. In this study, we analyzed the microbiomes of human fetal lung as early as the first trimester and corresponding placentas. A major novel finding was the existence of a human fetal microbiome signature, as early as the first trimester. In conclusion, our analysis shows that a placental microbiome indeed exists and that it bears striking similarity to the human fetal lung microbiome based on overall microbiome analysis, as well as alpha and beta diversities.
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