Exploring the complexities of intestinal and pulmonary microbiota in cystic fibrosis: A multi-omics approach

Abstract

Background: We aimed to elucidate the cystic fibrosis (CF) microbiota composition (shotgun metagenomics) and functionality (short-chain fatty acids, SCFAs).

Methods: Fecal and sputum samples were recruited from 39 clinically stable CF subjects.

Results: Bacillota and Pseudomonadota were dominant in both gut and lung compartments, whereas Ascomycota were the most abundant fungi in feces, and Basidiomycota, especially Malassezia globosa, in sputum. Viruses accounted for 0.4 % of the relative abundance in the gut and 0.6 % in lungs. Mycobacteroides abscessus was genetically identified in 10 individuals, although only 2 had positive cultures. Patients with higher levels of Pseudomonas filamentous phages had negative cultures for P. aeruginosa. The protozoan Toxoplasma gondii was detected in all sputum samples, accounting for 0.25 % of the metagenomic reads, with further PCR-confirmation in 50 % of subjects, including children. No correlation was found between SCFA and lung function or microbial composition. The resistome of the fecal compartment was higher than that of the lungs, and a greater abundance of SCFAs in the intestine was associated with poorer lung function.

Conclusions: Patients with normal-mild lung function had higher alpha diversity in the respiratory microbiota; however, beta diversity in the stool was statistically different compared with the group with poorer lung function. Although there were no differences in SCFA concentrations, butyrate-producing bacteria were more abundant in the sputum of the group with better lung function. In fecal samples, resistome to tetracyclines, glycopeptides, and aminoglycosides predominated, whereas in sputum an enrichment of ARGs related to tetracyclines, beta-lactams, and macrolides was observed.