Microbial Bioactives
Microbial Bioactives | Online ISSN 2209-2161
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Volume 9 Number 1 2026
REVIEWS (Open Access)
Microbial Bioactive Metabolites in Cystic Fibrosis: Drivers of Chronic Lung Infection and Novel Therapeutic Targets
Nafiz Tareq Hasnain 1*, Manish Mittal 1, Pallab Paul 1
Microbial Bioactives 9 (1) 1-21 https://doi.org/10.25163/microbbioacts.9110765
Submitted: 08 April 2026 Revised: 21 May 2026 Accepted: 05 June 2026 Published: 07 June 2026
Abstract
Cystic fibrosis (CF) lung disease has traditionally been understood as a consequence of defective ion transport, impaired mucociliary clearance, and persistent bacterial colonization. Yet recent advances in metabolomics, microbiome science, and immunology suggest that this explanation, while still fundamentally valid, may capture only part of the disease process. Increasingly, the CF airway is being recognized as a metabolically active ecosystem in which host-derived lipids, microbial metabolites, inflammatory mediators, and immune signaling pathways interact continuously to shape chronic pulmonary injury. This narrative review synthesizes current evidence regarding microbial bioactive metabolites and their contribution to airway inflammation, pathogen adaptation, oxidative stress, and therapeutic resistance in CF. Particular attention is given to sphingolipid dysregulation, short-chain fatty acids, quorum-sensing molecules, immunometabolites such as succinate and itaconate, and gut–lung axis signaling. The review further explores the growing therapeutic relevance of natural bioactive compounds, sphingolipid modulators, and CFTR-targeted therapies in controlling chronic inflammatory and metabolic dysfunction. Collectively, the evidence suggests that microbial metabolites are not passive byproducts of infection but active regulators of airway ecology and disease persistence. Although important mechanistic uncertainties remain, emerging metabolomic insights may ultimately help redefine CF management through precision immunometabolism and multi-target therapeutic strategies aimed at disrupting the metabolic conditions that sustain chronic airway disease.
Keywords: Cystic fibrosis, Microbial bioactive metabolites, Immunometabolism, Sphingolipids, Pseudomonas aeruginosa, Chronic lung inflammation, Precision therapeutics
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