Gut Microbiome Slow to Develop, Offer ‘Normal Benefits’ in CF Infants
Bacteria living in the gut are abnormally slow to develop functional abilities in infants with cystic fibrosis (CF), which may affect their nutrition, growth, and gastrointestinal health, a study reported.
Therapies targeting the gut microbiome could be “promising avenues” to improving their overall health, its researchers suggested.
The gut is home to billions of bacteria and other microorganisms — collectively called the gut microbiome — that play a crucial role in normal health and digestion. Normally, the gut microbiome develops and changes a lot in the first year of life, which is partly driven by the introduction of foods other than milk in the diet.
Pancreatic insufficiency and inflammation are known CF digestive problems, and prior research has shown that the gut microbiome is abnormal in infants with this disease. However, the consequences of these alterations are not well understood.
A team of scientists in the U.S. and Israel conducted metagenomic analyses to better understand how the microbiome’s ability to function is altered by CF. Their analyses involved genetic sequencing of bacteria present in microbiome samples, followed by computer analyses based on these data to identify biological pathways with altered activity.
The researchers analyzed 1,157 fecal samples collected from 207 infants with CF over the first year of life. For comparison, 122 samples collected from 25 healthy infants also were analyzed.
Significant differences were evident between the groups in several aspects of microbiome function at 4 months old, and especially at 12 months of age. Among 6-month-old infants, most differences trended in the same direction, though many were not statistically significant — which the researchers said is likely a result of dietary transition (i.e., starting to eat baby food) at around this age.
Statistical analyses showed that differences observed in the gut microbiome were largely not attributable to differences in diet or antibiotic use; instead, they likely reflect changes brought on by CF itself.
“We found that fecal microbiota functional capacities in healthy infants and infants with CF diverge during the first year of life,” the team wrote. “By 12 months of age, the resulting differences included multiple [biological pathways] related to bacterial metabolism and interaction with the environment.”
In other analyses, the researchers looked at how the gut microbiome’s function tended to change over time. They found that the development of the gut microbiome was delayed in infants with CF — essentially, the microbiomes of infants with CF “looked younger” than those of similarly aged healthy infants. This difference was apparent as early as 4 months of age, and progressively grew larger with increasing age.
“We found that the fecal samples from infants with CF displayed nonsignificant trends toward delayed development in metagenomic functional capacities starting at month 4, increasing in magnitude over time, resulting in significant delays by month 12,” the researchers wrote.
This delay “may indicate that CF gut microbiota cannot provide the normal benefits of a healthy gut microbiome during infancy,” they added.
Researchers then conducted analyses looking for factors associated with altered microbiome function among infants with CF. They found significant differences between infants fed breast milk and those fed formula, and also between those who were or weren’t on antibiotics at the time of sampling.
Further analyses looked at the specific bacteria and metabolites responsible for these differences. For example, the researchers found that bacteria in a class called Bifidobacterium played a notable role in determining functional differences between CF infants fed breast milk or formula.
“The role of Bifidobacterium as a primary contributor to diet-dependent differences in infant fecal functional capacities is consistent with previous observations of relatively increased fecal abundances of Bifidobacterium in breastfed infants and their known capacities for metabolizing glycans [chain-like structures composed of single sugar molecules] that differ between formula and breast milk,” the researchers wrote.
Bifidobacterium bacteria also were tied to variations in bile acids, which are digestive components used to break down fats, among other duties. Abnormalities in the workings of bile acid are thought to be involved in a wide range of CF-associated digestive problems, such as a reduced ability to regulate fats and sugars, the researchers stated.
The team suggested that therapies targeting these differences in gut bacteria may be a useful strategy for improving digestive health in CF.
“Our results suggest that dietary or probiotic approaches targeting abundances or functions of specific [types of bacteria in the gut] could improve diverse health outcomes in infants with CF and related disorders,” the researchers wrote.
“For example, modulating the intestinal levels of Bifidobacterium [and other types of bacteria] would be predicted to affect bile acid abundances in the CF infant gut, potentially improving nutritional, intestinal, and hepatic [liver-related] outcomes,” they added.