MICROBIOTA-PATHOGEN INTERACTİONS AND MICROBIOME-BASED THERAPEUTIC STRATEGIES

The human respiratory tract microbiome is a dynamic ecosystem that plays a critical role in shaping host defence mechanisms and influences virtually every stage of infection pathogenesis. For many years, the lower respiratory tract was thought to be sterile, but advanced molecular sequencing approaches have shown that it harbours a low-density but ecologically structured microbiome. This community directly influences the course of respiratory tract infections through colonisation resistance, mucosal barrier integrity, and regulation of the immune response. Viral infections, intensive antibiotic use, smoking, environmental toxins, and chronic lung diseases such as COPD and cystic fibrosis can reduce microbial diversity, leading to the proliferation of opportunistic pathogens and disruption of the inflammatory balance. This situation facilitates the colonisation of pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Pseudomonas aeruginosa, thereby increasing the risk of pneumonia, ventilator-associated infections, and bacterial superinfections. Immune regulatory signals transmitted via the gut-lung axis, the production of short-chain fatty acids, and adaptive immune balance can determine susceptibility to respiratory tract infections. Therefore, dysbiosis is considered not merely a local microbial alteration but a complex process involving systemic inflammatory imbalance. Loss of microbial diversity, weakened immune regulation, and impaired barrier functions have become a new clinical target area in infectious disease medicine. Compositional and functional changes in the respiratory tract microbiome are proposed as potential biomarkers that could predict infection risk and clinical course. In this context, microbiome-based therapies include emerging biotherapeutic approaches such as probiotics, prebiotics, postbiotics, phage therapy, and bacterial consortia. Rather than focusing solely on eliminating pathogens, these strategies aim to restore microbial balance and support the host’s immune tolerance. Integrating multiomic data with artificial intelligence-assisted analyses may help clarify the complex interactions between the microbial ecosystem and the host, and open new avenues for more personalised approaches to infection management. Although the current evidence is promising, clinical questions such as dosage, strain selection, safety, and long-term efficacy remain unanswered. Overall, this section aims to incorporate the respiratory microbiome's pathogenic interactions and treatment targets to bring a microbiome perspective to infection management. This approach may become an important component of personalised infection treatment in the future.