Early Answers

Study analyzes how gestational age influences gut microbiome

Microbial DNA is present in the gut of developing fetuses and differs by gestational age at birth, according to a study published in the November print issue of The FASEB Journal. Using advanced culture and DNA sequencing techniques, researchers at Le Bonheur Children’s Hospital/University of Tennessee Health Science Center analyzed samples of meconium to explore neonatal gut microbial communities.

“For the last hundred years, scientists have believed that the human fetus developed, protected from the outside world, in a womb that – unless something went terribly wrong – remained sterile and completely isolated from the host of bacteria, fungi and viruses that waited to make us sick when we emerged into the outside world,” said lead author Kent Willis, MD. “This belief was largely based on the fact that it was very difficult to grow cultures of live microorganisms from this part of the body.”

Recent studies have challenged that theory, and scientists are learning more about the early colonization of microorganisms inside the womb.

Willis’s team collected meconium samples from both very low birth weight preterm and term-born infants to study how gestational age affects a newborn’s microbial DNA. Factors considered in data collection included prenatal and postnatal antibiotic exposure, prenatal steroid exposure, delivery mode and illness severity. Researchers characterized microbial findings using both culture-independent and culture-dependent techniques.

“We found that the largest determinant of the amount and type of fungi detected is the infant’s gestational age at birth,” said senior author Joseph F. Pierre, PhD. “This suggests that the fungal DNA we detected is not the result of random contamination of the uterus or colonization following birth, but rather is highly associated with the age at which the infant leaves the womb.”

Understanding the order and timing in which microorganisms colonize the intestines is important, the researchers say, because therapeutic interventions, like perinatal antibiotics, may affect the gut’s mature microbiome at birth and play a crucial role in disease development.

For instance, findings showed that preterm birth was highly correlated to the presence of Candida, a potentially pathogenic type of fungi.

“This suggests that, unlike the majority of the fungi we studied, these fungi might contribute to the disease process of preterm birth,” said Willis.

In recent years, the gut’s microbiome has received substantial attention as scientists discover more about the role it plays in an individual’s health. Studies have linked diversity of gut bacteria and fungi to everything from food allergies and obesity to cancer and mental health.

The UTHSC team is continuing to follow study participants to determine whether the meconium samples, or additional samples collected in the weeks following, are correlated with later disease risk and growth parameters.

K.A. Willis, J.H. Purvis, E.D. Myers, M.M. Aziz, I. Karabayir, C.K. Gomes, B.M. Peters, O. Akbilgic, A.J. Talati, and J.F. Pierre. Fungi form interkingdom microbial communities in the primordial human gut that develop with gestational age, The FASEB Journal, In Press, August 2019, https://doi.org/10.1096/fj.201802655RR