Accepted_test

The state of the microbiocenosis of the lower respiratory tract (LRT) is a decisive factor for maintaining the respiratory function of patients with cystic fibrosis (CF). For chronically infected patients, restoration of the microbiota of the RT requires the selection of complex therapy. Key to the comparative study of the microbiome of samples are the methods of molecular phylogenetics. We applied a phylogenetic protocol to a multivariate study of samples from adult CF patients chronically infected with clinically significant Pseudomonadota (csP) to determine the effectiveness of therapies including antibacterial and targeted drugs. Sanger sequencing of Pseudomonadota genes and massively parallel sequencing of 16S rDNA were used in the analysis of 103 sputum samples from 52 adult CF patients. Alpha and beta diversity of samples in groups, and biomarkers were examined using the CLC Genomic Workbench package and the LEfSe algorithm. Phylogenetic diversity (PD) was significantly reduced in samples from patients chronically infected with csP, patients with severe pulmonary disease and in exacerbation/antibiotic therapy, and when the proportion of Staphylococcus increases above 30%. PD was independent of targeted therapy and mutation severity. When the microbiome was restored, an imbalance was observed for many oral commensals entering the lower respiratory tract through microaspiration (Streptococcus, Prevotella, Rothia). Thus, the return of balanced diversity of the lung microbiome in chronically infected adult patients with CF is possible with long-term complex therapy and attention to representatives of all taxa that make up the biotope of the LRT, which can be identified by molecular phylogenetics methods.