CHILDREN with cystic fibrosis showed lower short chain fatty acids, associated with dietary patterns and inflammation.
Short Chain Fatty Acids in Cystic Fibrosis
Early life changes in fecal short chain fatty acid concentrations may help explain why many children with cystic fibrosis experience persistent gastrointestinal symptoms and inflammation. In a prospective longitudinal observational study, investigators compared 64 children with cystic fibrosis with 64 age matched healthy controls. Participants completed a validated food frequency questionnaire and provided stool samples for targeted liquid chromatography mass spectrometry short chain fatty acid profiling, fecal calprotectin testing, and 16S rRNA sequencing of the gut microbiota.
The analysis identified marked depletion of valerate and isobutyrate in children with cystic fibrosis, with greater variability over time than in controls. Typical age associated increases seen in healthy children for butyrate, valerate, isobutyrate, and isovalerate were absent in the cystic fibrosis group, suggesting an altered developmental trajectory of fecal short chain fatty acid concentrations.
Diet, Diversity, and Intestinal Inflammation
Within the cystic fibrosis cohort, butyrate tracked with broader ecosystem measures. Higher fecal butyrate was associated with greater microbial alpha diversity, and lower butyrate correlated with higher fecal calprotectin, linking reduced short chain fatty acids with intestinal inflammation signals.
Dietary patterns also differed. Children with cystic fibrosis reported a higher relative intake of total fat, predominated by trans and saturated fats, alongside lower relative intake of fiber, wholegrains, and resistant starch. The authors propose that limited dietary fiber and depletion of key short chain fatty acid producing taxa may push the microbiome toward alternative, less efficient pathways of butyrate synthesis. When butyrate is reduced, heightened inflammation appears more likely, based on the observed relationship with fecal calprotectin.
The findings also highlight knowledge gaps around less studied metabolites. The physiological roles of valerate and isobutyrate in cystic fibrosis remain unclear, and the authors call for further work to clarify the clinical implications of their depletion, including whether targeted nutritional strategies could help stabilize fecal short chain fatty acid concentrations in early life.
Reference: van Dorst J et al. Children with cystic fibrosis have an early-life disparity in fecal short chain fatty acid concentrations. Journal of Cystic Fibrosis. 2026; doi:10.1016/j.jcf.2026.01.002.
