Human foetal lungs harbour a microbiome signature, find researchers

In a first time finding, researchers discover that the lungs and placentas of foetuses in the womb as young as 11 weeks after conception already show a bacterial microbiome signature, which suggests that bacteria may colonise the lungs well before birth.

The finding deepens the mystery of how the microbes or microbial products reach those organs before birth and what role they play in normal lung and immune system development. The study was published in the American Journal of Respiratory and Critical Care Medicine.

A team led by the University of Alabama at Birmingham researcher Charitharth Vivek Lal, MD, found that a human fetal microbiome DNA signature is present in the lungs as early as the first trimester.

This foetal lung microbiome showed changes in diversity during foetal development, suggesting microbiome maturation with advancing gestational age. Finally, a placental microbiome was also present in human foetal tissue, and this microbiome signature showed some taxonomic overlap with the corresponding human foetal lung microbiome.

"We speculate that maternal-foetal microbial DNA transfer, and perhaps of other microbial products and whole live or dead bacteria is a realistic possibility," said Lal, an associate professor in the UAB Pediatrics Division of Neonatology. "This may serve to 'prime' the developing innate immune system of the foetus and help in the establishment of a normal host-commensal relationship."

Denise Al Alam, PhD, an investigator in The Saban Research Institute of Children's Hospital Los Angeles and assistant professor of pediatrics at the University of Southern California, is the first author who spearheaded the concept of the study.

Researchers, including Lal and colleagues, have previously seen that the lungs of infants, sampled immediately after birth, are colonized with bacteria. Furthermore, similar microbiome profiles are found after either cesarean or vaginal delivery, which suggested that microbes somehow are able to reach the lungs before birth.

In the new study, 31 samples of lung, placenta and intestine tissue from foetuses between 11 and 20 weeks of gestation were collected. Duplicate, independent tests done in labs at Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, and at UAB detected bacterial DNA in all samples. The two labs used different DNA extraction kits and different microbiome analysis pipelines.

Bacterial DNA was detected through targeted analysis of the bacterial gene for 16S ribosomal RNA, which is a standard method to distinguish different microbial taxa. The initial 16S analysis in Singapore showed 48 unique taxa in the lung samples, 11 unique taxa in placenta samples and 24 shared taxa.

The 16S analysis of the same samples at UAB showed two separate human foetal lung microbiome groups, based on foetal age - one group at 11 to 15 weeks' gestation, and the other at 16 to 20 weeks' gestation. Furthermore, the two gestational age groups showed a significant change in microbiome diversity with time.

"Overall, at both lab sites," Lal said, "analysis of the bacterial taxa distribution and diversity showed some overlap in microbiome signatures of foetal lungs and matched placentas.