reported having found microbial DNA in the meconium (i.e., first stool). Josef Neu speculated on the implications of these and other recent microbiome research in pediatric populations. For example, that the first stool contains microbes suggests not only that a fetal microbiome exists, but also that its existence could relate to prematurity.

Fetal Microbiome: Clinical Implications

Evidence of microbes in the meconium refutes the popular notion that the mammalian fetal intestine is sterile and that the first exposure to maternal microbiota occurs during passage through the birth canal, according to Neu. Goldenberg and colleagues (2000) suggested that first exposure could occur during the last trimester of pregnancy, that is, babies are bathed in amniotic fluid that may contain microbes that have ascended from the vagina and translocated through the choriodecidual membrane. DiGiulio and colleagues (2008) examined the possibility by analyzing stored amniotic fluids of babies born at various gestational times. Using both culture-based and polymerase chain reaction (PCR) techniques, they found that gestational age was inversely correlated with microbial presence and quantity. In other words, babies born prematurely had more microbes in their amniotic fluids. The researchers also reported a positive correlation between both their culture and PCR results and amniotic fluid concentrations of white blood cells and interleukin-6 (IL-6), suggesting that microbial presence and quantity are associated with intestinal inflammation. Nanthakumar and colleagues (2000) had previously reported an inverse relationship between maturity and IL-8 expression, also suggesting that prematurity could be associated with an intestine-derived inflammatory response to microbes swallowed by the fetus through the amniotic fluid.

Together, these data suggest that when microbes are swallowed by the fetus, the ensuing infection increases the output of inflammatory mediators (e.g., IL-6, IL-8) and thereby potentially triggers premature labor as well as other problems (e.g., necrotizing enterocolitis, chronic lung disease, neurodevelopmental delays). Because amniotic fluid is difficult to sample, the next best evidence available for testing this hypothetical scenario comes from the baby’s first stool. “If you think of it from the perspective that the baby’s meconium is actually a reflection of what has been going on in utero in terms of the swallowing of the microbes,” Neu said, “meconium could potentially be a very valuable source of information.” Using data from meconium samples, he and his colleagues reported lower microbial diversity among less mature babies (Mshvildadze et al., 2010). More recent, unpublished data also show correlations between gestational age and phylum-level diversity—for example, a fairly strong negative correlation between gestational age and Actinobacteria (Triplett and Neu, unpublished



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