Although the use of antibiotics in premature
babies to ward off or treat potentially deadly bacterial infections is a lifesaver,
they also cause long-lasting collateral damage to the developing microbial
communities in the babies’ intestinal tracts, according to research from
Washington University School of Medicine in St. Louis.

A year and a half after babies leave the
neonatal intensive care unit (NICU), the consequences of early antibiotic
exposure remain, the study showed. Compared to healthy full-term babies in the
study who had not received antibiotics, preemies’ microbiomes contained more
bacteria associated with disease, fewer species linked to good health, and more
bacteria with the ability to withstand antibiotics.

The findings, published in Nature
Microbiology, suggest that antibiotic use in preemies should be carefully
tailored to minimise disruptions to the gut microbiome – and that doing so
might reduce the risk of health problems later in life.

“The type of microbes most likely to
survive antibiotic treatment are not the ones we typically associate with a
healthy gut,” said senior author Gautam Dantas, PhD, a professor of
pathology and immunology, of molecular microbiology, and of biomedical
engineering. “The makeup of your gut microbiome is pretty much set by age 3,
and then it stays pretty stable. So, if unhealthy microbes get a foothold early
in life, they could stick around for a very long time. One or two rounds of
antibiotics in the first couple weeks of life might still matter when you’re

Healthy gut microbiomes have been linked to
reduced risk of a variety of immune and metabolic disorders, including
inflammatory bowel disease, allergies, obesity and diabetes. Researchers
already knew that antibiotics disrupt the intestinal microbial community in
children and adults in ways that can be harmful. What they didn’t know was how
long the disruptions last.

To find out whether preemies’ microbiomes
recover over time, Dantas and analysed 437 faecal samples collected from 58
infants, ages birth to 21 months. Forty-one of the infants were born around 2.5
months premature, and the remainder were born at full term.

All the preemies had been treated with
antibiotics in the NICU. Nine had received just one course, and the other 32
each had been given an average of eight courses and spent about half their time
in the NICU on antibiotics. None of the full-term babies had received

The researchers discovered that preemies
who had been heavily treated with antibiotics carried significantly more
drug-resistant bacteria in their gut microbiomes at 21 months of age than
preemies who had received just one course of antibiotics, or full-term infants
who had not received antibiotics. The presence of drug-resistant bacteria did
not necessarily cause any immediate problems for the babies because most gut
bacteria are harmless – as long as they stay in the gut. But gut microbes
sometimes escape the intestine and travel to the bloodstream, urinary tract or
other parts of the body. When they do, drug resistance can make the resulting
infections very difficult to treat.

Moreover, by culturing bacteria from faecal
samples taken eight to 10 months apart, the researchers discovered that the
drug-resistant strains present in older babies were the same ones that had
established themselves early on.

“They weren’t just similar bugs, they were
the same bugs, as best we could tell,” Dantas said. “We had cleared an opening
for these early invaders with antibiotics, and once they got in, they were not
going to let anybody push them out. And while we didn’t show that these
specific bugs had caused disease in our kids, these are exactly the kind of
bacteria that cause urinary tract and bloodstream infections and other
problems. So, you have a situation where potentially pathogenic microbes are
getting established early in life and sticking around.”

Further studies showed that all the babies
developed diverse microbiomes by 21 months of age – a good sign since lack of
microbial diversity is associated with immune and metabolic disorders in
children and adults. But heavily treated preemies developed diverse microbiomes
more slowly than lightly treated preemies and full-term infants. Further, the
makeup of the gut microbial communities differed, with heavily treated
premature infants having fewer healthy groups of bacteria such as Bifidobacteriaceae and
more unhealthy kinds such as Proteobacteria.

The findings already have led Warner, who
takes care of premature infants in the NICU at St. Louis Children’s Hospital,
and her fellow neonatologists to scale down their use of antibiotics.

“We’re no longer saying, ‘Let’s just start
them on antibiotics because it’s better to be safe than sorry,’” Warner said.
“Now we know there’s a risk of selecting for organisms that can persist and
create health risks later in childhood and in life. So, we’re being much more
judicious about initiating antibiotic use, and when we do start babies on
antibiotics, we take them off as soon as the bacteria are cleared. We still
have to use antibiotics – there’s no question that they save lives – but we’ve
been able to reduce antibiotic use significantly with no increase in adverse
outcomes for the children.”


Reference: Gasparrini AJ, et al. Persistent
metagenomic signatures of early-life hospitalization and antibiotic treatment
in the infant gut microbiota and resistome. Nature Microbiology. Published 9
September 2019.