Abstract
BACKGROUND: Cystic fibrosis (CF) is a genetic disorder that disrupts gut microbiota composition, promoting dysbiosis associated with chronic inflammation, impaired nutrient absorption, and poor clinical outcomes. While modulation of the intestinal microbiota through prebiotics, probiotics, and synbiotics has been proposed as a therapeutic strategy, clinical evidence remains limited, especially in children. OBJECTIVE: This study aimed to evaluate the impact of three supplementation strategies (a prebiotic (β-glucan), a probiotic (Lacticaseibacillus rhamnosus GG), and their synbiotic combination) on the gut microbiota and metabolic activity of a CF child faecal donor using a dynamic in vitro colonic fermentation model (SHIME(®)). METHODS: Microbial composition (16S rRNA gene sequencing), and metabolic activity (quantification of short-chain fatty acids (SCFAs), ammonia, and lactate) were analysed. RESULTS: Results showed that the prebiotic increased alpha diversity; while both the prebiotic and probiotic treatments significantly reduced Bacillota and increased Bacteroidota, modulating the Bacillota/Bacteroidota ratio. The synbiotic treatment showed the most beneficial overall profile, including enhanced production of SCFAs, particularly butyrate and propionate, and increased abundance of Faecalibacterium and Agathobacter, which are two bacterial genera generally associated with gut health. Notably, the synbiotic also reduced the relative abundance of potentially pathogenic genera such as Veillonella, Megasphaera, and Stenotrophomonas, but paralleled with an increase in Clostridium ss 1. Although the probiotic alone showed some positive effects, it was less effective overall compared to the prebiotic and synbiotic approaches. CONCLUSIONS: These findings support the potential of synbiotic supplementation as a promising strategy to modulate gut dysbiosis in CF, though in vivo studies are needed to confirm the translational relevance of these results.