Live Biotherapeutics Drug Discovery Service for Cystic Fibrosis
Overview
Cystic fibrosis (CF) is associated with intestinal dysbiosis, local and systemic inflammation, and impaired immune function. The disease is characterized by thickened secretions, changes in pulmonary microbial diversity, and progressive airway infection caused by pathogenic microorganisms. CF has a reduced abundance and species richness of the gut microbiota compared to healthy individuals. Intestinal flora imbalance is an important cause of severe intestinal inflammation and intestinal structural and functional changes in CF patients. Most of the bacteria that were significantly reduced in CF gut microbiota, such as Ruminococcaceae (mainly F. prausnitzii), Bifidobacterium species, and Lactobacillus species, also had associated anti-inflammatory properties. Taken together, alterations in the gut microbiota in CF may delay respiratory impairment and highlight the potential benefits of ameliorating systemic inflammation and enhancing immune capacity. Probiotics are a particularly attractive strategy that has recently emerged as a prophylactic agent to prevent or delay pulmonary colonization by CF pathogens, and also as a therapeutic tool to eventually combat established pulmonary infections.
Fig.1 Schematic diagram of the bidirectional crosstalk between gut microbiota and the lungs.1
Mechanism of Action of Probiotics
The protective effect of probiotics against pathogenic microorganisms is mainly based on three biological processes: antimicrobial activity, immunomodulation, and supporting epithelial barrier properties. The antimicrobial activity of probiotics is associated with the production of antimicrobial agents such as bacteriocins, which compete for limited substrates and cell adhesion sites and inhibit the production of virulence factors, hydrogen peroxide, and organic acids that acidize ecosystems. Airway epithelial cells have pattern recognition receptors, which can quickly sensitively respond to microbial threats and initiate immune responses.
Probiotics as a Therapeutic Strategy in CF
Alterations in the gut microbial environment are thought to contribute to intestinal inflammation and subsequent barrier impairment in CF. Targeted alteration of the gut microbiome in CF is the focus of innovation to alter disease expression, and therapies that alter the gut microbiome include targeted antibiotic therapy, prebiotic or commensal therapies, probiotic therapies, dietary interventions, and microbiome or fecal transplantation. Probiotics have been the most rigorously studied; a mouse model of probiotic intervention found that administration of L. casei improved clearance of Pseudomonas aeruginosa from the lungs and treated bacterial and viral pneumonia. Several studies have found that Lactobacillus can modulate allergic pulmonary inflammation and CF exacerbation. Direct delivery of probiotics into the respiratory tract (by aerosol or nasal inoculation) may enhance the therapeutic efficacy of probiotics because this route allows the direct effects of probiotics on pulmonary pathogens while modulating the local immune response.
Our Probiotic Services for CF Research
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Research Articles
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Available Services
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Antibacterial and antibiofilm effects of lactobacilli strains against clinical isolates under conditions relevant to cystic fibrosis.2
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Effect of lactobacillaceae probiotics on colonic microbiota and metabolite production in cystic fibrosis.3
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References
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Yuksel, Nilufer, Busra Gelmez, and Ayca Yildiz-Pekoz. "Lung microbiota: its relationship to respiratory system diseases and approaches for lung-targeted probiotic bacteria delivery." Molecular Pharmaceutics 20.7 (2023): 3320-3337.
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Batoni, Giovanna, et al. "Antibacterial and antibiofilm effects of Lactobacilli strains against clinical isolates of Pseudomonas aeruginosa under conditions relevant to cystic fibrosis." Antibiotics 12.7 (2023): 1158.
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Asensio-Grau, Andrea, et al. "Effect of Lactobacillaceae Probiotics on Colonic Microbiota and Metabolite Production in Cystic Fibrosis: A Comparative In Vitro Study." Nutrients 15.17 (2023): 3846.
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Distributed Under Open Access license CC BY 4.0, without modification.
For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.
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