Gut microbiota plays a key role in human health. Not only does it help humans obtain energy and essential nutrients from food, but it also, crucially, trains the immune system. For a long time, it was assumed that immune education started after birth, when maternal microorganisms began to colonize the newborn’s intestine. Now, a new study reveals that immune training may have begun much earlier than previously thought: during pregnancy.

According to new research led by Yale University scientists, components of the gut microbiota initiate maturation in utero. In the absence of intestinal bacterial colonization, the team detected bacterial byproducts in the fetus’ gut, which they suspect are transferred from mother to baby through the placenta.

According to new research, components of the gut microbiota initiate maturation in utero

In a recent paper, published in the Journal JCI Insight, the scientists suggest that the early exposure to microbial components may be both priming the immune system to be educated about beneficial bacteria, so it does not overreact when it subsequently encounters those microorganisms, and preparing the gastrointestinal tract.

There have been previous suggestions about immune education starting before birth. For instance, human data from malaria studies has shown that malaria-specific fetal immune responses are generated during pregnancy and confer protection later in life. Furthermore, the fact that most babies are born healthy and do not suffer from neonatal infections despite being exposed to microorganisms suggests their immune system may not be as immature and poorly functional as was long believed.

In that regard, Yale professor Liza Konnikova and her team, who have studied for several years how the immune system develops in the human gastrointestinal tract, have also found evidence of mature adaptative immune cells in fetuses in utero.


But how are those immune cells being trained?

To answer that question, the researchers studied 31 intestinal samples from children at three different developmental phases: fetal stage, infancy, and older children. Almost all the bacterial byproducts or metabolites identified were found in all samples, suggesting microbial components are present before birth.

The scientists also saw that each group of children had unique metabolites, although groups closer in age shared more of those components than those showing a greater age difference, meaning metabolites are linked to developmental stages. Surprisingly, they identified that the bacterial byproducts found in 14- to 23-week-old fetuses were different from the postnatal ones. Also, they detected several food metabolites in the samples, such as vitamins B1 and B5, likely ingested by the mother.

Despite being unable to provide proof, the scientists believe the metabolites detected in the fetuses are likely to be maternal, produced by or in response to the mothers’ gut microbiota. They hypothesize that, through those bacterial components, mothers are in fact providing the elements needed to boost the baby’s immunity before birth, thus improving their chance of survival.



Li Y,  Toothaker JM, Ben-Simon S et al. In utero human intestine harbors unique metabolome, including bacterial metabolites. JCI Insight, 2020;5(21):e138751. DOI: