New study finds gut bacteria differences in children with CF
Reduced beneficial compounds and increased inflammation seen
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Children with cystic fibrosis (CF) have lower gut levels of certain short-chain fatty acids (SCFAs), metabolites made by beneficial gut bacteria that help regulate inflammation, a study reports.
The researchers also found that children with CF had lower dietary fiber intake, reduced gut microbial diversity, fewer key SCFA-producing bacteria, and higher levels of gut inflammation.
“Further work is needed to elucidate the mechanisms involved, and to determine whether modifiable factors or therapeutic interventions can meaningfully improve [SCFA] concentrations and reduce intestinal inflammation,” the team wrote.
Study examines gut compounds and inflammation in children with CF
The study, “Children with cystic fibrosis have an early-life disparity in fecal short chain fatty acid concentrations,” was published in the Journal of Cystic Fibrosis.
The thick, sticky mucus that characterizes CF can cause widespread complications throughout the digestive tract, especially affecting the intestines, pancreas, and liver.
Research suggests that people with CF often have fewer gut bacteria that break down dietary fiber into SCFAs. These bacterial metabolites play important roles in the body, including helping regulate metabolism, immune function, and brain health.
Yet, no studies to date have directly measured fecal SCFA concentrations in children with CF, the researchers wrote.
To help address this gap, scientists in Australia examined how SCFAs, gut microbiota (the community of microorganisms living in the gut), diet, and inflammation are related in children with CF.
Stool samples reveal differences in gut compounds and diet
The team collected stool samples from 64 children with CF, ages 3 months to 16 years, and from 64 healthy children matched by age. The majority of children with CF were pancreatic insufficient, meaning their pancreas could not produce or release enough digestive enzymes. About one-fifth (20%) were receiving CFTR modulator therapy.
Analysis of stool samples showed significantly lower levels of two SCFAs, valerate and isobutyrate, in children with CF compared with healthy children. In healthy children, levels of four SCFAs — butyrate, valerate, isobutyrate, and isovalerate — were significantly higher after age 3, but this age-related increase was not seen in children with CF.
Dietary questionnaires showed that children with CF consumed more fats — especially trans and saturated fats — and less fiber, whole grains, and digestible-resistant starch than healthy children. They also had higher intake of omega-3 fatty acids, retinol (vitamin A), and vitamin B12. The researchers did not find a direct link between overall macronutrient intake and fecal SCFAs.
Levels of fecal calprotectin, a marker of gut inflammation, were higher in children with CF and were linked to lower levels of butyrate, a beneficial SCFA. This association was not seen in healthy children. Higher calprotectin levels were also linked to diets higher in trans fats, saturated fats, fatty meats, dairy, noncore (“junk”) foods, sweet drinks, sodium, vitamin B12, and calcium.
Gut microbial diversity, the variety and abundance of different bacteria, was lower in children with CF. This difference became more pronounced with age. In children with CF, lower microbial diversity was also linked to lower butyrate levels, which have been associated with increased gut inflammation.
“When butyrate is reduced, heightened inflammation is more likely,” the team wrote.
Gut bacteria linked to inflammation more common in CF children
The three types of bacteria most enriched in the gut of children with CF were Enterococcus, Enterobacter, and Rhodococcus. Higher levels of Enterococcus and Enterobacter were linked to lower levels of butyrate. Higher Enterococcus levels were also associated with lower levels of valerate, isobutyrate, and isovalerate in both CF and healthy children.
Several other beneficial bacteria involved in producing butyrate were also found at lower levels in children with CF. These included Faecalibacterium, Pseudobutyrivibrio, Roseburia, Subdoligranulum, Coprococcus, Ruminococcaceae, and Lachnospiraceae.
Higher levels of Enterococcus and Rhodococcus were also associated with increased calprotectin levels, a marker of gut inflammation. Similar associations were seen with Veillonella, Tyzzerella, Peptoclostridium, and Pediococcus.
Many participants continued providing stool samples for a little more than two years. During this time, microbial richness (the number of bacterial species) decreased significantly in children with CF. Levels of valerate, isobutyrate, and isovalerate also varied more widely than in healthy children, indicating greater instability, the team noted. However, the researchers said that this analysis over time was limited because the healthy controls were older.
“Our findings indicate that reduced microbial diversity, depletion of key SCFA-producing [bacterial families], and limited dietary fibre intake may promote alternative, less efficient pathways of butyrate synthesis in [CF children],” the scientists wrote. “Further investigation into the physiological roles of valerate and isobutyrate is needed to understand the implications of their depletion in CF.”
