Babies born by caesarean section, as well as those given antibiotics early in life, have a different balance of gut microbes than other babies, two new studies show. These differences could put them at higher risk for various health problems in childhood, including asthma, type 1 diabetes, and perhaps even autism.
By the time children are three years old, their microbiomes are largely stable, said Dr. Ramnik Xavier, a lead author on one of two related studies published Wednesday in Science Translational Medicine. So what happens early in life can have long-term implications for health.
"The take-home message is that not allowing the immune system to develop to its maximum potential … is not a good thing," said Xavier, chief of the gastrointestinal unit at Massachusetts General Hospital. "You need the microbiome to develop normally and educate the immune system in the gut to respond to these microbes and also prevent other harmful bugs from getting in."
His study followed 39 Finnish children from birth to age three, while the other study, from New York University, tracked 43 youngsters in New York City.
Families in both places delivered the contents of dirty diapers to clinics, which stored them in freezers to keep the fecal microbes intact until scientists could extract DNA and identify the thousands of bacterial species hiding inside.
Both studies showed that kids prescribed antibiotics in their first few years had a different balance of microbes than those who did not need the medications. They also found different cohorts in children born by C-section compared to vaginal delivery.
Earlier studies had suggested the same results, but the new research analyzed the microbiome more deeply and followed the same children over a period of time, said Xavier, who is also an affiliate of the Broad Institute.
The microbiomes of children born by C-section look less mature than those delivered vaginally, said Dr. Martin Blaser, a professor at NYU who headed the second study. Even if their microbiomes do eventually catch up, "there's still a period of time when the microbiome is not maturing at the same rate as the baby," he said.
Whether diseases like type-1 diabetes are a direct result of an altered microbiome is still an open question.
The studies do have limitations. Most notably, that they can't prove cause-and-effect. Most children receive antibiotics because they are sick. So maybe the illness itself, and not the medication, is to blame for the changes in the baby's microbiome.
And women who have C-sections are usually given antibiotics during the procedure. So maybe it's the antibiotics that alter the microbiome, not the C-section, said Dr. Tim Buie, a pediatric gastroenterologist at Massachusetts General Hospital, who was not involved in the new research.
Regardless, Blaser urged women to be cautious when choosing a C-section for convenience, rather than for medical reasons. The C-section rate in the United States is 32 percent; the rate in Manhattan, where his study was done, is even higher.
Bacterial diversity is so complex that the difference among strains can be as vast as the gap between Great Danes and dachshunds, said Dr. David Relman, a professor at Stanford Medical School, who was not involved in either study, though he does similar research.
Xavier said he was shocked by the number of antibiotics his test subjects have received. Of the 39 children, half received no antibiotics, while the others received nine to 15 doses in their first three years. "I guess it's not uncommon when you prescribe an antibiotic for a viral infection and kids don't get better, for the physician to write another prescription," Xavier said.
Those who got the antibiotics showed signs of having antibiotic-resistant bacteria in their guts — potentially setting them up for medications that may not be effective later.
Blaser said he hopes to get funding so he can follow the children in his study as they proceed through elementary school and beyond.
Buie said the next step is to figure out how to rebalance a child's bacterial community, once it's disturbed.
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