We are born as empty vessels, emerging from the sterile conditions of the womb to be rapidly colonized by microbes from our mothers. As we grow and wean over the next three years, those colonists—our first microbiome—matures too. In predictable waves, some bacteria rise to power while others fade into obscurity. And as they change, they also change us. They collectively shape the development of our gut, train our budding immune system, and process our food. Their influence is so profound that if they don’t mature correctly, they could increase the risk of conditions like malnutrition, type 1 diabetes, and asthma.
In recent years, many scientists have been ringing alarm bells about aspects of modern life that are supposedly upsetting the early establishment of our microbiome, jeopardizing our health. C-sections, for example, mean that babies first encounter microbes from skins and hospital environments, rather than the usual vaginal species. And antibiotics, doled out to treat infectious diseases, also assault the microbes that infants depend upon. In some experiments, mice gain weight when exposed to antibiotics as pups, raising concerns that these drugs could also be driving the human obesity epidemic, along with other “modern plagues”
This is a nice story, and one that’s being told more and more—but when you look closer, you can see plot holes.
Through studies in mice and people, it’s clear that C-sections and antibiotics can change the microbiome. But there’s a tendency to assume that these changes are bad, that they last, and that they matter. And I’m not sure we have enough evidence to warrant any of those conclusions.
Consider two new studies, published today, one led by Moran Yassour and Ramnik Xavier from the Broad Institute and the other by Nicholas Bokulich and Martin Blaser from New York University. The two teams collected stool samples from babies, 39 and 43 of them respectively, over their first three years of life.
Both showed that a common group of bacteria called Bacteroides is conspicuously rare from the guts of first-year infants born through C-sections. Is that a disruption? Is it a bad thing inflicted on the microbiome by an unnatural birth? Not quite. Xavier’s team also saw that a fifth of their vaginally delivered babies had the same low-Bacteroides signature, for reasons they still don’t understand.
And just last month, Xavier’s team published a paper linking high Bacteroides levels in infants to poorer health. These microbes dominate the guts of Finnish and Estonian infants, and they silence the developing immune system at a time when it must acclimate to the microbes it commonly encounters. This might explain why Finland and Estonia have relatively high rates of early-onset autoimmune diseases, caused by panicky, hyperactive immune systems that haven’t been properly calibrated. It might also explain why such diseases are rare in Russian infants, who carry far lower levels of Bacteroides.
What about other microbes? Last year, in a study of 319 babies, a Canadian team found a connection between low levels of four bacteria with anti-inflammatory properties and later risk of asthma. C-sections have been linked to higher asthma risk, so you’d expect that babies delivered this way would have low levels of the same bacterial quartet. Not so: in Blaser’s study, two of the four—Lachnospira and Veillonella—were overrepresented in the guts of C-section infants.
To summarise: ¯\_(ツ)_/¯
We still don’t really understand what these microbes are doing, so we can’t infer what their absence or presence implies. A change might be good or bad, depending on a multitude of circumstances, such as a baby’s genes or the other bacteria that it carries.
The two new studies also found that antibiotics reduce the diversity of species in the microbiome, both within individual infants and between them as a group. Xavier’s team showed that the drugs destabilize the bacterial communities, making them more prone to fluctuations, while Blaser’s group found that they delay the rate at which the microbes mature into their adult state.
But in both studies, the drugs had small and temporary effects. They changed things, but only by a bit, and never permanently. The microbes quickly recover and catch up. By the time the antibiotic-treated infants celebrated their first or second birthdays, their gut microbiomes were just as diverse and resilient as those of their drug-free peers. Indeed, despite the much-hyped connection between early antibiotic use and obesity, Xavier’s team found no such link: the babies who took antibiotics didn’t put on any more weight than those who avoided the drugs.
The microbiomes of C-section babies also veer back on course, so that after a year, they’re more or less the same as those of babies born vaginally. One of the largest microbiome studies so far, which I covered in April, supports this view: it found that adult microbiomes aren’t affected by C-sectional birth.
So, childhood antibiotics and C-sections seem like waves that rock the Good Ship Microbiome without ever capsizing it. The ship rights itself in the end, and goes along its way.
That doesn’t mean the waves don’t matter. Those early years are critical times in a baby’s life, and Blaser’s team argues that any disturbances during this window “are likely to have strong effects on development of the microbiota and potentially for host health.”
Other studies support this idea. In February, Jeffrey Gordon’s team showed that the gut microbiomes of malnourished Malawian infants mature slower than usual. The babies end up with communities that are less efficient at harvesting energy from food, which contributes to their low weight and weak bones. But even in that study, the team couldn’t tell why the microbiomes stalled in the first place. Possible culprits include gut diseases, poor diets, antibiotics, or combinations of all of the above.
The point is: we don’t know. Future studies—preferably with sample sizes beyond the low dozens—will hopefully provide some answers. But for now, the quest to understand the human microbiome is as much in its infancy as the babies that Ramnik and Blaser worked with. It’s a field that needs to move away from simply looking for changes to working out if those changes matter, from finding statistical significance to establishing actual significance.
