How a baby is born has a profound impact on their microbiome — the community of microbes that colonize the body.
That’s the finding of the largest ever study of the newborn microbiome, which offers the strongest evidence yet that children born through the vaginal canal carry different microbes from those delivered by caesarean section. Newborns delivered by c-section, the study found, tend to lack strains of gut bacteria found in healthy children and adults. Instead, their guts harbour harmful microbes that are common in hospitals.
The study, which analysed nearly 600 births in the United Kingdom, did not look at whether these microbial differences can affect health later in life. But the presence of disease-causing bacteria is a concern, says Trevor Lawley, a microbiologist at the Wellcome Sanger Institute in Hinxton, UK, who led the work1, published in Nature on 18 September. “The level of colonization by health-care pathogens is shocking in these children. When I first saw the data, I couldn’t believe it,” he says.
Previous research has hinted that babies delivered by c-section fail to acquire some of the microbes from their mothers that vaginally delivered children gain. This observation has led some parents to swab infants born by c-section with vaginal fluids, in an attempt to restore any missing microbes. But the practice, known as vaginal seeding, is controversial and its safety and effectiveness are unproven. Lawley says limitations of past studies — such as their small size and limited sampling — means that it was not clear whether the way a baby is born affects their microbiota.
Working with midwives and doctors at three hospitals in London and Leicester, Lawley’s team sampled and analysed the DNA of microbes found in the faeces of 596 babies — 314 born vaginally and 282 by c-section — at 4, 7 and 21 days after birth.
The differences between their gut microbiotas were clear-cut. Babies born by c-section lacked strains of commensal bacteria — those typically found in healthy individuals — whereas these bacteria made up most of the gut community of vaginally delivered infants. Instead, the guts of c-section babies were dominated by opportunistic bacteria such as Enterococcus and Klebsiella, which circulate in hospitals. The difference was so stark, Lawley says, that “I could take a sample from a child and tell you with a high-level certainty how they were born.”
Months after birth, however, the infants’ microbiotas grew more similar — with the exception of a common genus of commensal bacteria called Bacteroides. These bacteria were absent or present at very low levels in the microbiotas of nearly all c-section babies after birth. Nine months later, on average, around 60% of these babies still harboured few or no Bacteroides in their guts. Previous research has suggested that some species of Bacteroides influence the immune systems of their hosts and help to quell inflammation.
To better assess the microbes that tended to colonize the guts of the c-section babies, Lawley’s team cultured hundreds of bacteria strains from faecal samples. Genome sequencing identified genes responsible for antibiotic resistance and virulence, and confirmed that the strains were related to the opportunistic bacteria that tend to be found in hospitals.
Lawley’s study is part of larger effort, called the Baby Biome Study, which aims to follow thousands more newborns into childhood. Epidemiological studies have suggested that children born by c-section have an increased risk of asthma and obesity later in life. Lawley says that, by studying enough children, his team should be able to determine whether the mode of birth — and the accompanying changes in microbiota — are behind these health associations.
But factors beyond the method of delivery probably contribute to the differences in microbiota, says Josef Neu, a neonatologist at the University of Florida College of Medicine in Gainesville. Mothers who have c-section births receive antibiotics that can cross the placenta. Their babies also tend to spend longer in hospital and receive microbe-filled breast milk later than infants born vaginally.
Rob Knight, a microbiologist at the University of California, San Diego, says the study could help to identify specific microbe strains that could be given to c-section babies to make their microbiotas resemble those of vaginally delivered babies. He has previously conducted a small trial2 of vaginal seeding, and he performed the procedure with his wife after their daughter was born by emergency c-section in 2011.
Lawley, who co-founded a company to deliver microbial therapies, says it might be possible to alter the newborn microbiota in this way. But he stresses that his team’s latest study offers no support for vaginal seeding. “The idea of putting undefined microbes in children that are immunologically underdeveloped is very risky,” says Lawley. “Our data does not that support that. It makes me very nervous.”
Shao, Y. et al. Nature https://doi.org/10.1038/s41586-019-1560-1 (2019).
Dominguez-Bello, M. G. et al. Nature Med. 22, 250–253 (2016).