Poor Gut Microbiota in Infants with CF Linked to Stunted Growth in 1st Year of Life, Study Suggests

An imbalance in the microbes that populate the gut of infants with cystic fibrosis (CF) affects their growth throughout the first year of life.

This finding was detailed in the study “Fecal dysbiosis in infants with cystic fibrosis is associated with early linear growth failure” published in the journal Nature Medicine.

Most infants with CF have low linear growth (length for age) across their first 12 months of life, which also affects their lung development. Previous studies have found a link between poorer linear growth in these infants, and poorer respiratory function and survival in the long-term.

An estimated 85% of CF infants are also known to have exocrine pancreatic insufficiency — deficiencies in pancreatic enzymes  needed to properly digest food. This insufficiency is a cause the gastrointestinal inflammation, problems with digestion, and poor nutrient absorption that can result in poor weight gain.

These gastrointestinal symptoms can also contribute to a phenomenon called intestinal dysbiosis — an imbalance in the populations of microbes naturally present in the gut. The intestinal microbe populations (also called the microbiota) play a pivotal role in body growth by harvesting nutrients in the gut, regulating host metabolism, and producing substances that influence growth hormone levels.

Researchers at the University of Washington used fecal samples from infants with CF to investigate a possible link between their gut microbiota and linear growth between the ages of 3 and 12 months.

The study included 207 CF infants with either low or normal body length, and 25 age-matched healthy infants serving as controls. Samples were collected from all the babies starting at 3 months old to determine “whether microbiota development appears similar in trajectory.”

Results showed that infants with CF at age 4 months had a lesser diversity of bacteria species in their fecal samples overall than did healthy babies. This bacterial diversity improved in the CF babies over their first year of life, but to a lesser extent than was evident in the control group.

During the same time period, the proportions among different groups of bacteria were also found to be different in CF infants compared to healthy infants. Specifically, the relative abundances of Proteobacteria was higher in CF infants and that of Bacteroidetes was lower. Prior studies have shown that fat malabsorption and inflammation are associated with a fecal enrichment of Proteobacteria and depletion of Bacteroidetes.

The proportions of bacteria groups found in samples were also significantly different between CF infants with low linear growth (a shorter length) and CF infants with normal linear growth at 12 months old. Specifically, shorter CF infants had a more pronounced dysbiosis (imbalance in intestinal microbe populations).

Researchers then used a mathematical model to establish a relationship between an infant’s age and their fecal microbiota. Using this method, they saw that infants with CF, overall, had a delayed maturation of fecal microbiota compared to controls. Delays in maturation were particularly pronounced in CF infants of shorter length at 12 months old compared to infants with this disease but normal body length for that age.

“Therefore, low length was associated with delayed fecal microbiota development in infants with CF,” the researchers wrote.

The team also found that CF infants had a lower proportion of bacteria species involved in the production of short-chain fatty acids (SCFA) — molecules known to modulate bone and body growth.

“These results suggest that SCFA production by intestinal microbiota of infants with CF may be diminished compared with that of infants without CF,” the researchers wrote, suggesting that “fecal dysbiosis may contribute to inadequate length achievement by altering SCFA production.”

This work suggests that “therapies that address the early fecal dysbiosis exhibited here in infants with CF, or that replenish SCFAs or modulate their production (such as with prebiotics, as supported by a recent study) may improve early growth, GI [gastrointestinal] function, and long-term CF outcomes,” the researchers concluded.