Effectiveness of Probiotics, Prebiotics, and Symbiotic Supplementation in Cystic Fibrosis Patients: A Systematic Review and Meta-Analysis of Clinical Trials

Abstract

Background and Objectives: Cystic fibrosis (CF), caused by CFTR gene mutations, primarily affects the respiratory and gastrointestinal systems. Microbiota modulation through probiotics, prebiotics, or synbiotics may help restore microbial diversity and reduce inflammation. This study aimed to evaluate their efficacy in CF. Materials and Methods: A systematic review and meta-analysis of randomized controlled trials (RCTs) published between 2000 and 2024 was conducted in Cochrane, ScienceDirect, Web of Science, LILAC, BMC, PubMed, and SCOPUS following PRISMA guidelines. Methodological quality was assessed using the Jadad scale, and RevMan 5.4^® estimated effects on pulmonary function (FEV₁), exacerbations, hospitalizations, quality of life, and inflammatory markers. Results: Thirteen RCTs (n = 552), mostly in pediatric populations, were included. Most examined probiotics (e.g., Lactobacillus rhamnosus GG, L. reuteri), while four used synbiotics. Several studies reported reduced fecal calprotectin and proinflammatory interleukins (e.g., IL-6, IL-8), suggesting an anti-inflammatory effect. However, no significant differences were observed regarding hospitalizations or quality of life. Additionally, none of the studies documented serious adverse events associated with the intervention. The meta-analysis showed no significant decrease in exacerbations (RR = 0.81; 95% CI = 0.48-1.37; p = 0.43) or improvements in FEV₁ (MD = 4.7; 95% CI = -5.4 to 14.8; p = 0.37), even in subgroup analyses. Sensitivity analyses did not modify the effect of the intervention on pulmonary function or exacerbation frequency, supporting the robustness of the findings. Conclusions: Current evidence suggests that probiotics or synbiotics yield inconsistent clinical benefits in CF, although some reduction in inflammatory markers may occur. Larger, multicenter RCTs with longer follow-up are needed for clearer conclusions. Until more definitive evidence is available, these supplements should be considered experimental adjuncts rather than standard interventions for CF management.

Keywords: cystic fibrosis; dysbiosis; microbiota; probiotics; systematic review.

Figure 1

PRISMA flow diagram with the search and study selection strategy.

Figure 2

Risk of bias evaluation for the studies included in this review. (a) The “+” symbol denotes low risk of bias, “?” indicates unclear risk, and “–” represents high risk of bias. The colors associated with each symbol are green for low risk, yellow for unclear risk, and red for high risk. (b) This panel shows a summary of the identified risk of bias across all evaluated studies, displaying the percentage corresponding to each risk-of-bias item [33,34,35,36,37,38,39,40,41,42,43,44,45].

Figure 3

Forest plots of the effect of probiotic supplementation on FEV₁ in patients with CF [33,34,35,37,38,39,42,45].

Figure 4

Subgroup analysis forest plots of the effect of probiotic supplementation on FEV₁ in CF patients according to intervention duration [33,34,36,37,38,39,42,45].

Figure 5

Subgroup analysis forest plots of the intervention’s effect on FEV₁ in CF patients according to the type of administered product [33,34,36,37,38,39,42,45].

Figure 6

Subgroup analysis forest plots of probiotic supplementation on FEV₁ in CF patients according to the number of used strains [33,34,36,37,38,39,42,45].

Figure 7

Forest plots of the effect of probiotic supplementation on pulmonary exacerbations in CF patients [33,34,38,39,42].

Figure 8

Subgroup analysis forest plots of the effect of probiotic supplementation on CF patients’ pulmonary exacerbations according to intervention duration [33,34,38,39,42].

Figure 9

Subgroup analysis forest plots of the effect of probiotic supplementation on CF patients’ pulmonary exacerbations according to the number of used strains [33,34,38,39,42].