The surprising hitchhikers that we pass to our babies
By Beth Skwarecki
There’s no question that human milk is a biological powerhouse. In addition to providing excellent nutrition for a baby, this maternally produced sustenance includes antibodies, immune cells, natural antibiotics, and antivirals.
It also contains “prebiotic” food for the bacteria and other tiny organisms — collectively known as microbes — that live in a baby’s gut, nourishing them and keeping the colonies healthy. Maybe you’ve already heard about that. But did you know that breast milk also contains the microbes themselves? Wait until you learn where they come from.
Scientists are finding microbes everywhere — and that’s because they are everywhere. The Human Microbiome Project, a federally funded project aimed at identifying all of the bugs that call the human body home, sampled 18 body sites and found truly humbling numbers: We harbor 10,000 microbial species that collectively express 8 million genes. Just to give some perspective, humans express just over 20,000 genes.
And while gut microbes get the lion’s share of the headlines (after all, most of our microbial buddies live in the intestines) the microbes in the other parts of the body do some amazing things too. These tiny friends swarm in the human mouth, nose, vagina, and armpit — and the exact makeup of our microbes differs from person to person.
Actually, “everywhere” doesn’t mean only the surfaces of our bodies. We used to think that healthy urine was bacteria free, but that’s not necessarily true. Microbes have also been found in brain tissue. We used to think healthy lungs were sterile, too, but nope. Until about 2008, the accepted dogma was that a fetus, floating tranquilly inside its mother’s uterus, was in a microbe-free, pure state. And we thought mother’s milk, the first thing many babies consume, was also sterile, that it picked up any bacteria from surfaces during transfer from mother to child.
We thought wrong. Instead of sterility being the rule, passing down germs from mother to child may be an essential part of reproduction.
“Babies are born without a fully developed intestinal mucosa, and need interaction with bacteria to basically jump start their immune system,” says Lisa Funkhouser, who co-authored a paper with Seth Bordenstein last month on the many ways mothers across the animal kingdom transmit microbes to offspring.
What’s most fascinating about the microbes in breast milk and those that a fetus harbors before birth is where they originate. The idea is still in its, um, infancy, but evidence is accumulating that cells in the bloodstream pick up microbes from the intestine and transport them to destinations in milk-producing breast tissue … and across the placenta to the developing fetus.
The evidence for hitchhiking bacteria
This idea first appeared in the work of a group of Swiss and French scientists who put a few facts together: First, babies’ guts contain the “good” species of bacteria even though the infant immune system isn’t really up to the task of sorting out good from bad. Second, bacteria occur even in human milk that’s been collected with a sterilized pump and an antiseptic on the mother’s skin. And third, white blood cells readily travel from the gut and lungs into breast milk, which suggested that microbes could be delivered by hitching a ride on these cells.
So these researchers put this idea to the test. They found matching strains of bacteria in maternal feces, blood, and aseptically collected milk. Switching to mice for more invasive tests, they found that 70% of pregnant animals had bacteria in their lymph nodes, versus just 10% of non-pregnant mice. After birth, bacteria could be found in their milk ducts, and the patches of immune-system tissue in their intestines (one hypothesized boarding station for gut microbes) were enlarged.
This idea of an “enteromammary pathway” connecting the gut and breast is not without precedent. In 1979, researchers identified a similar pathway that brought antibodies from the gut to breast tissue. But antibodies are small particles compared to bacteria, and the concept that microbes might also use such a pathway came much later.
The cells making up our intestines are sewn tightly to each other in what are called tight junctions. In 2001, researchers found that white blood cells can reach an “arm” through the junction and take samples of the bacteria in our partially digested food slurry. A perspective article cheekily referred to this as “Periscope up!”, and this behavior gained a reputation as the immune system’s regular patrol for pathogens, including taking a prisoner to pick apart.
But when the white blood cells capture bacteria, bacterial death isn’t always the goal. The bacteria in breast milk are alive. A study published earlier this month filled in some of the puzzle of how they evade death. The researchers, led by microbiologist Christophe Lacroix, used a constellation of techniques to show that identical strains of bacteria are found in the maternal gut, maternal milk, and the infant gut and that these bacteria are viable in all three places.
A weakness in most new studies of our microbiome is that they rely on DNA sequencing technology that can’t tell the difference between living and dead microbes, Lacroix says. So the best evidence for live bacteria being carried through the blood comes from a combination of sequencing and culture-based methods.
Think of culture as smearing some bacteria on a Petri dish, as microbiologists have been doing since Fanny Hesse taught her husband to make agar gel in 1882. Now consider the many differences between that dish and the inside of the human intestine. A few microbes, like E. coli, grow well in both environments, but plenty of bacteria (not to mention fungi, archaea, and viruses) have been identified only from scraps of their DNA. Some have called these bacteria unculturable, but Lacroix just sees them as more of a challenge.
Lacroix’s study demonstrates how tough it is to figure out just which microbes are riding around in the body. It was hard to find matching bacteria in all three samples, possibly because of technical difficulties. Because trillions of bacteria live in the gut, any sample is likely to underemphasize a lot of lower-abundance species. In fact, the investigators got a triple match in only one of their seven mother–baby pairs, although several pairs showed matches in two out of three. Still, the results are unlikely to be a fluke. Since contamination from skin or surfaces could have thrown them off, Lacroix’s team took the clever step of focusing on bacteria that can’t grow on surfaces exposed to air.
Lacroix concludes that evidence for bacteria hitching rides from the gut to milk tissue is “quite strong,” but what would really seal the deal would be to find living bacteria in blood samples, basically catching the bacterial passengers on their commute.
Microbes in the womb?
Microbes in breast milk are only half the story. Evidence also suggests that mothers pass microbes to fetuses in the womb, as well. For one thing, live bacteria have been found in the umbilical cord blood of healthy babies. Bacteria can also be found in meconium, the clinical name for baby’s first poop. Meconium consists of the leftovers of what the fetus accumulated while in the womb: dead cells, mucus, bile, and other appetizing ingredients which would include bacterial leftovers if bacteria are present in the womb. Indeed, in a particularly exciting mouse study, researchers fed tagged bacteria to pregnant females. After delivering the pups by sterile c-section, the investigators found the tagged bacteria in the pups’ meconium.
Obviously, that kind of research can’t be done quite that way in humans, “but it really raises the bar about how much further we have to delve into these questions,” says Bordenstein. “We’re at a tipping point of our knowledge, and the current paradigms will probably change in the next few years. There’s a surface of bubbling interest in the idea the womb is not sterile.”
That’s great, but … why?
“In the breast milk you have quite a broad ecosystem. So why would there be such an ecosystem if it has no real features for delivering some sort of property to the baby?” Lacroix asks. Based on ongoing experiments, he thinks that a special group of microbes is important for setting up a healthy ecosystem in the infant gut. Some of their products fuel our own cells while others support yet more microbes. After all, an ecosystem has many layers, and Lacroix believes these tiers establish themselves during the first six months of life.
But are human cells deliberately capturing these microbes (and perhaps selecting specific species) in the “taking prisoner” approach of white blood cells reaching through intestinal gaps, or are the microbes hijackers? Clues suggest that animals do the selecting. Bordenstein has tested species of insects that, despite the same diet, develop predictably different microbial ecosystems. “There’s got to be a host control of the microbiome at some level,” he says, probably directed by the immune system.
Of course, babies fill out their microbiomes through other means, too. We know that infants born vaginally have a different microbe profile from those born by caesarian section, and that formula-fed babies have a different profile from those who are breastfed. If these differences are relevant to infant and child health, it might be possible to use microbes as a preventative therapy for kids at risk. Many studies on breast milk bacteria (including Lacroix’s) are funded by Nestle, which is particularly interested in developing a better probiotic-enhanced formula. There are probiotic formulas on the market already, but they have shown limited and mixed results on infant health. Enhancing the number of species or their mode of delivery could help, for example, premature infants who can’t breastfeed.
Time will tell. “We are in this stage of perpetual discovery and exploration,” Bordenstein says. “The microbiome is at a stage where we were a hundred years ago with genetics.”