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Bacteria Are In the Developing Baby By the Second Trimester

We've known for a while that exposure to microbes during the baby's first year is important (and good) for the developing immune system. In addition, recent research suggests that during the second trimester of pregnancy the developing fetus already has microbes in its body which help "educate" the developing immune system.

An international team of researchers found that bacterial species are present in the fetus during the second trimester. They examined and found bacteria in the  gut, lungs, skin, and placenta of the fetuses. Gardnerella, Lactobacillus, and Staphylococcus species were found in most of the fetal organs. Streptococcus, Enterococcus, and Prevotella species were also frequently found, as well as other species. The view is that the microbes came from the mother ("vertical transmission of microbes").

What the researchers found exciting was not just that there were microbes living already in the fetus in the second trimester, but that these microbes "educate" the developing immune system, especially memory T cells. This prepares the newborn with all sorts of exposures (including harmful microbes) once it is born.

The researchers used genetic sequencing (16S ribosomal RNA sequencing) on fetal and placental tissues, which were obtained from second trimester (starting with week 13) abortions.

Excerpts from The Scientist: Microbes in Human Fetuses Spur immune Development

Over the last decade, scientists have shown that the fetal immune system comes online much sooner than was initially thought, but what type of antigens train nascent immune cells and how this affects subsequent development remain open questions. In a study published June 1 in Cell, researchers determined that second-trimester human fetuses harbor live bacteria in tissues all over their bodies that can activate fetal T cells. 

In 2017, immunologist Florent Ginhoux of A*STAR in Singapore and colleagues showed that the fetal immune system is operational by the second trimester of pregnancy. “It looks like the fetal immune system is quite functional quickly and early,” he explains.

The findings ran contrary to the long-held assumption that babies receive their first big immune challenge when they are born and come into contact with the outside world, starting with the vaginal microbiome, he adds. While work from other groups has confirmed the second trimester appearance of the fetal immune system, it’s still not clear what antigens fetal immune cells recognize.

To answer this question, Ginhoux again teamed up with Jerry Chan and Salvatore Albani of the Duke-NUS Medical School in Singapore and Naomi McGovern, a former postdoc at A*STAR who now runs her own lab at the University of Cambridge in the UK. The researchers used 16S ribosomal RNA sequencing on various fetal and placental tissues—obtained from abortions during the second trimester—to show that there were traces of microbes present in the fetal gut, lungs, and skin, as well as in the placenta.

The team grew live bacteria from fetal tissue in culture, including some of those specific microbes that were not found in the controls. Then, they prepared fetal guts—the tissue that showed evidence of the largest microbial community, aside from the skin—for scanning electron microscopy. The gut tissue came from one fetus at 10 weeks estimated gestational age and three at 14 weeks estimated gestational age.

“To our surprise, we could find microbes” in the guts of the 14-week-old fetuses, but not the 10-week-old, Ginhoux says, which suggests that the bacteria colonize the gut after a certain point in development. The bacteria were located only in specific areas in the intestinal lumen, in structures that looked as though they were bound to mucin, a mucus-like substance released by epithelial cells.

Finally, the researchers showed that some of the bacterial species they found in the fetuses could activate memory T cells isolated from fetal tissues in an in vitro system they designed to monitor T cell activation and expansion. “The T cells that we find activated in the tissue, some of them are likely to have been educated or have been activated to respond to the microbes that were isolated,” Ginhoux explains. The findings indicate that microbes are one of the factors involved in early human immune development and “may be the basis for that lifelong human health and immunity.”

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