Disrupted Intestinal Microbiota and Intestinal Inflammation in Children with Cystic Fibrosis and Its Restoration with Lactobacillus GG: A Randomised Clinical Trial

Abstract

Background & AimsIntestinal inflammation is a hallmark of cystic fibrosis (CF). Administration of probiotics can reduce intestinal inflammation and the incidence of pulmonary exacerbations. We investigated the composition of intestinal microbiota in children with CF and analyzed its relationship with intestinal inflammation. We also investigated the microflora structure before and after Lactobacillus GG (LGG) administration in children with CF with and without antibiotic treatment.MethodsThe intestinal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE), real-time polymerase chain reaction (RT-PCR), and fluorescence in situ hybridization (FISH). Intestinal inflammation was assessed by measuring fecal calprotectin (CLP) and rectal nitric oxide (rNO) production in children with CF as compared with healthy controls. We then carried out a small double-blind randomized clinical trial with LGG.ResultsTwenty-two children with CF children were enrolled in the study (median age, 7 years; range, 2–9 years). Fecal CLP and rNO levels were higher in children with CF than in healthy controls (184±146 µg/g vs. 52±46 µg/g; 18±15 vs. 2.6±1.2 µmol/L NO2 −, respectively; P<0.01). Compared with healthy controls, children with CF had significantly different intestinal microbial core structures. The levels of Eubacterium rectale, Bacteroides uniformis, Bacteroides vulgatus, Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Faecalibacterium prausnitzii were reduced in children with CF. A similar but more extreme pattern was observed in children with CF who were taking antibiotics. LGG administration reduced fecal CLP and partially restored intestinal microbiota. There was a significant correlation between reduced microbial richness and intestinal inflammation.ConclusionsCF causes qualitative and quantitative changes in intestinal microbiota, which may represent a novel therapeutic target in the treatment of CF. Administration of probiotics restored gut microbiota, supporting the efficacy of probiotics in reducing intestinal inflammation and pulmonary exacerbations.Trial RegistrationClinicalTrials.gov NCT 01961661

Impact of cystic fibrosis disease on archaea and bacteria composition of gut microbiota

“…This difference in biodiversity was lower than that previously reported among younger subjects (Bruzzese et al. 2014). Figure 1b presents the dendrogram produced using software analysis.…”

“…2014). Our analysis of the Clostridium coccoides group utilized previously reported primers and thermal protocol (Maukonen et al.…”

“…vulgatus and Faecalibacterium prausnitzii as previously described (Bruzzese et al. 2014). Table 1 lists the remaining qPCR primers.…”

“…2013; Bruzzese et al. 2014). Results of these studies commonly describe reductions of members of the Bacteroides - Prevotella group, Bifidobacterium spp.…”

“…To the best of our knowledge, there are no studies showing a clear relationship between reduced microbiota complexity and inflammation in CF; in one study (Bruzzese et al. 2014), the authors attempted to correlate bacterial biodiversity with fecal calprotectin (CLP) values but no association was found.…”