AI Article Synopsis
- G551D is a mutation in cystic fibrosis (CF) that affects chloride channels, and ivacaftor is a treatment that improves symptoms in patients with this mutation.
- A study involving 20 CF patients evaluated the effects of ivacaftor on their airway microbiome over four months, comparing it to a placebo, but found no significant difference in microbiota composition between the two treatments.
- However, changes in microbiota were linked to antibiotic exposure rather than ivacaftor itself, and a small subgroup showed reduced bacterial load during ivacaftor treatment when antibiotic exposure remained unchanged.
Article Abstract
Background: G551D is a class III mutation of the cystic fibrosis transmembrane regulator (CFTR) that results in impaired chloride channel function in cystic fibrosis (CF). Ivacaftor, a CFTR-potentiating agent improves sweat chloride, weight, lung function, and pulmonary exacerbation rate in CF patients with G551D mutations, but its effect on the airway microbiome remains poorly characterised.
Methods: Twenty CF patients with at least one G551D mutation from a single centre were recruited to a 4month double-blind, placebo-controlled, crossover study of ivacaftor with 28days of active treatment. Sputum microbiota composition was assessed by 16S rRNA gene amplicon sequencing and quantitative PCR at five key time points, along with regular clinical review, respiratory function assessment, and peripheral blood testing.
Results: No significant difference in microbiota composition was observed in subjects following ivacaftor treatment or placebo (PERMANOVA P=0.95, square root ECV=-4.94, 9479 permutations). Microbiota composition variance was significantly greater between subjects, than within subjects over time (P<0.0001, Mann Whitney U test), and an additional within-patient paired assessment of microbiota similarity was therefore performed. Again, change in microbiota composition was not significantly greater during treatment with ivacaftor compared to placebo (Wilcoxon test, P=0.51). A significant change in microbiota composition was however associated with any change in antibiotic exposure, regardless of whether ivacaftor or placebo was administered (P=0.006). In a small, subgroup analysis of subjects whose antibiotic exposure did not change within the study period, a significant reduction in total bacterial load was observed during treatment with ivacaftor (P=0.004, two-tailed paired Student's t-test).
Conclusions: The short-term impact of ivacaftor therapy on sputum microbiota composition in patients with G551D mutations are modest compared to those resulting from antibiotic exposure, and may be masked by changes in antibiotic treatment regimen.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jcf.2017.08.002 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Lactococcus lactis and Bifidobacterium bifidum alleviate postmenopausal symptoms by suppressing NF-κB signaling and microbiota dysbiosis.
Sci Rep
December 2024
Neurobiota Research Center, College of Pharmacy, Kyung Hee University, Seoul, 02447, Korea.
To understand the action mechanism of probiotics against postmenopausal symptoms, we examined the effects of Lactococcus lactis P32 (P) and Bifidobacterium bifidum P45 (P), which suppressed interleukin (IL)-6 and receptor activator of nuclear factor-κB (RANK) ligand (RNAKL) expression in Gardnerella vaginalis (Gv)-stimulated macrophages, on vaginitis, osteoporosis, and depression/cognitive impairment (DC) in mice with vaginally infected Gv, ovariectomy (Ov), or Ov/Gv (oG). Oral administration of P or P decreased Gv-induced DC-like behavior and tumor necrosis factor (TNF)-α, IL-6, RANK, and/or RANKL expression in the vagina, bone, hypothalamus, hippocampus, and colon, while Gv-suppressed bone osteoprotegerin and brain serotonin and brain-derived neurotrophic factor (BDNF) levels increased. They partially shifted vaginal and gut dysbiosis in Gv-infected mice to the gut microbiota composition in normal control mice.
View Article and Find Full Text PDFAnalyzing bacterial networks and interactions in skin and gills of Sparus aurata with microalgae-based additive feeding.
Sci Rep
December 2024
Department of Microbiology, Faculty of Sciences, CEI·MAR-International Campus of Excellence in Marine Science, University of Malaga, Málaga, Spain.
The inclusion of microalgae in functional fish diets has a notable impact on the welfare, metabolism and physiology of the organism. The microbial communities associated with the fish are directly influenced by the host's diet, and further understanding the impact on mucosal microbiota is needed. This study aimed to analyze the microbiota associated with the skin and gills of Sparus aurata fed a diet containing 10% microalgae.
View Article and Find Full Text PDFLauric-α-linolenic lipids modulate gut microbiota, preventing obesity, insulin resistance and inflammation in high-fat diet mice.
NPJ Sci Food
December 2024
College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou, 310058, China.
Medium- and long-chain triacylglycerols (MLCTs) are regarded as healthy premium oils; however, the health benefits of novel MLCTs enriched with lauric and α-linolenic acids are still not fully understood. This study examined the health benefits of lauric-α-linolenic structural lipids (ALSL) and physical mixture (PM) with a similar fatty acid composition in mice with obesity induced by the high-fat diet (HFD). The data indicated that ALSL is more effective than PM in counteracting obesity, insulin resistance, hyperlipidaemia, liver injury, and systemic inflammation in HFD-induced mice.
View Article and Find Full Text PDFColon-targeted engineered postbiotics nanoparticles alleviate osteoporosis through the gut-bone axis.
Nat Commun
December 2024
Department of Orthodontics, Peking University School and Hospital of Stomatology, Beijing, China.
The potential for mitigating intestinal inflammation through the gut-bone axis in the treatment of osteoporosis is significant. While various gut-derived postbiotics or bacterial metabolites have been created as dietary supplements to prevent or reverse bone loss, their efficacy and safety still need improvement. Herein, a colon-targeted drug delivery system is developed using surface engineering of polyvinyl butyrate nanoparticles by shellac resin to achieve sustained release of postbiotics butyric acid at the colorectal site.
View Article and Find Full Text PDFHost dispersal relaxes selective pressures in rafting microbiomes and triggers successional changes.
Nat Commun
December 2024
Department of Marine Science, University of Otago, Dunedin, New Zealand.
What little we know about how microbiomes change over the course of host dispersal has been gleaned from simulations or snapshot sampling of microbiomes of hosts undertaking regular, cyclical migrations. These studies suggest that major changes in both microbiome richness and turnover occur in response to long-distance movements, but we do not yet know how rare or sporadic dispersal events for non-migratory organisms might affect the microbiomes of their hosts. Here we directly examine the microbiomes of rafting seaweed, leveraging host genomic analyses, amplicon sequencing, and oceanographic modelling to study the impacts of ecological dispersal of hosts on their microbiomes.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!