Baby gut bacteria fails to mature normally with CF, study finds
Disruptions seen in infancy may contribute to later dysfunction, poor health
Young children with cystic fibrosis (CF) have less mature gut bacterial growth over time than do their typically developing peers, according to a new U.S. study.
“Our findings demonstrate that the gut microbiota of infants with CF fails to undergo typical developmental maturation, instead remaining entrenched in a transitional-like community state,” the researchers wrote, noting that this leads to “lower levels of beneficial bacteria” in these children as they grow.
Calling the gut microbiota — the bacteria and other organisms that live in the human gut — “critical for early-life training of the developing immune system,” the scientists wrote that “disruptions to the microbiota during this time period [in early childhood] can lead to subsequent metabolic and immunologic dysregulation.”
The researchers, from the Dartmouth Geisel School of Medicine in New Hampshire, said further study of baby gut bacteria is needed, “with an ultimate goal of identifying microbiota-directed therapeutics” for children with CF.
The study, titled “Persistent delay in maturation of the developing gut microbiota in infants with cystic fibrosis,” was published in the journal Human Microbiome.
Investigating how the gut microbiome matures in CF children
The human digestive system is home to billions of bacteria and other microscopic organisms, collectively known as the gut microbiome. These gut bacteria have profound effects on human health that are only beginning to be understood.
The gut microbiome in a baby looks quite different from an adult’s microbiome. Over the first few years of life, as the baby grows and starts to eat solid foods, the microbiome normally changes dramatically, eventually reaching a mature state.
According to Benjamin Ross, PhD, the study’s lead author and an assistant professor of microbiology and immunology at the Geisel School of Medicine, “it’s been known that in healthy infants, the intestinal microbiome is very dynamic and changes over time as a consequence of how they’re delivered at birth, whether they’re breastfed or not, and when they transition to solid food, among other factors.”
Then, from ages 3 to 5, those changes “stabilize into an adult-like microbiome,” Ross said in a Geisel press release. “This process is key to healthy development.”
Here, the team of researchers used data from 40 infants with CF to assess how the gut microbiome grows during infancy in young children with the genetic disease. All of the children had stool samples collected over the first three years of life. To contextualize the data, the researchers compared their findings against data from thousands of typically developing children in a large database.
“We didn’t really know how that process played out in infants with CF, so we set out to study how the gut microbiome of infants with the disease matured and if that maturation process was different compared to healthy kids,” Ross said.
Our major conclusion was that in CF the microbiome really doesn’t change very much, so it’s essentially stunted or delayed in its maturation compared to healthy kids, and this failure to mature may contribute to poor health.
The results showed that, within the first year of life, there are clear differences in the gut microbiome of a baby with CF: Certain types of gut bacteria are present at distinctly different levels, the team found.
According to the study, “these data demonstrate that the species-level composition of the gut microbiota of infants with CF differs dramatically from that of non-CF infants.”
Further, analyses over time showed that, unlike their typically developing peers, the gut microbiome in young children with CF doesn’t undergo as much of a maturation process. Instead, that process stalls, so that children with CF continue to have a relatively immature gut microbiome even when they’ve reached the ages where the microbiome is usually mature.
As one example, Ross noted that the researchers “found a depletion of health-associated bacteria in the CF kids, including Faecalibacterium Prausnitzii, which is a bacterium that specializes in using dietary fiber as an energy source.”
That bacterium “is known to stimulate anti-inflammatory responses,” Ross noted. “Our major conclusion was that in CF the microbiome really doesn’t change very much, so it’s essentially stunted or delayed in its maturation compared to healthy kids, and this failure to mature may contribute to poor health.”
Researchers find link between baby gut bacteria, early antibiotics
People with CF are susceptible to bacterial lung infections, so they are often treated with antibiotics, which work as bacteria-killing drugs. But antibiotic treatment can impact healthy gut bacteria as well as disease-driving infectious bacteria, research has shown.
Analyses here indicated that there was a close connection between gut microbiome immaturity and the amount of antibiotics that patients had been given early in life. “Our data implicate antibiotics in driving at least some aspects of altered microbiota maturation,” the researchers wrote.
The team noted, however, that these data are complex to interpret — for example, kids with more severe CF may receive more antibiotics, which makes it difficult to draw any simple conclusions about cause and effect. As such, there is a need for future studies to delve into the underpinnings of abnormal gut microbiome development in CF, as well as to explore how abnormal gut bacteria development impacts patients’ health, the researchers stressed.
“Further investigation of prospective human cohorts or the use of animal models of CF will be needed to understand the causal underpinnings of CF-related microbiota alterations and their consequences for the host more fully,” the researchers wrote.
This type of research can also lay the groundwork for future studies that aim to promote a more normalized gut microbiome development in babies with CF, the team noted.
Ross said the team is hopeful that their research will ultimately lead to new treatment strategies.
“We hope this work can include testing and developing interventions, such as probiotics or dietary changes, that may help mitigate the effect of the disease on the microbiome or supplement it with aspects that will help rescue microbiome deficiencies,” Ross said.
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