But Indira Mysorekar from Washington University in St. Louis notes that the team only took samples from a region of fingerlike structures called the terminal villi, which transfer nutrients from the mother’s bloodstream into the fetus’s. “That area is not expected to have the bacteria, and there really hasn’t been much controversy about whether there is a microbiome there,” Mysorekar says. When other studies found placental microbes, they looked at different parts of the organ.
Aagaard adds that the Cambridge team used techniques that would minimize the odds of finding resident microbes, from washing samples in saline to using sequencing protocols that are unlikely to find bacteria in low abundances. She also says that the team too readily billed microbes as vaginal contaminants, even when they were seen in placentas that had been delivered through C-sections. “They’ve subtracted out stuff that in my mind doesn’t make a lot of sense to subtract out,” Aagaard says.
“In the end, any one of those things we have decided are contaminants could actually be” in the placenta, Parkhill says. “It comes down to judgment, and a balance of probabilities. Do we throw away decades of biological understanding of the sterility of the placenta, or do we take this very weak and sporadic signal, which [could be] due to contamination, and claim that it’s real?”
In some cases, new evidence has changed his mind. “If you’d asked me 10 years ago, I would have told you that the lung is sterile,” he says. “That’s not the case now. There is a community there.” Other tissues are more controversial: Claims about a brain microbiome have been met with skepticism, and Parkhill says that “a lot of the signals I see in brain-microbiota papers are clearly contamination.”
It is hard to prove a negative, of course, but for the placenta at least, scientists have come close: For decades, they’ve successfully bred sterile mice by removing the uterus of a pregnant female, bathing it in sterilizing chemicals, cutting the pup out in sterile conditions, and raising it in a sterile environment. If placenta microbes exist, and pass from mother to fetus, this technique should be impossible. It plainly isn’t. “It is a bit startling that we are having a debate given that the ultimate experiment for sterility in the womb has been performed repeatedly, and routinely, for more than half a century,” says Maria Elisa Perez-Muñoz from the University of Alberta. (Aagaard counters that this is an extreme procedure that would likely remove any resident prenatal microbes; “It’s awfully darn-tooting hard to make a germ-free animal,” she says.)
Mysorekar feels that the technical side of this debate obscures more interesting questions. Like: If the placenta is sterile, how does that happen? If the fetus develops in a microbiological vacuum for nine months, why doesn’t it go into immunological shock when it’s suddenly exposed to millions of bacteria at birth? Why do fetuses seem to have activated immune cells, which usually only activate on exposure to bacterial molecules? “It makes biological sense that there’s some [prenatal] exposure,” she says, and if not through the placenta, then “where and how is that happening?”