Longitudinal Changes in Nasal and Oral Microbiome and Antimicrobial Resistance Gene Profiles in Response to Human Fecal Microbiota Transplantation

ABSTRACT The gut-lung axis describes interactions between intestinal and respiratory mucosal systems through microbial, metabolic, and immune pathways, but the systemic impact of gut-targeted therapies on upper respiratory tract (URT) communities remains underexplored. We conducted a longitudinal study in adult patients undergoing fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) alongside healthy controls. Fecal, nasal, and oral samples were collected at baseline (Day 0) and on Days 14 and 56 following FMT. Shotgun metagenomic sequencing was performed to quantify microbial diversity, taxonomic composition, and the abundance of antimicrobial resistance genes (ARGs). FMT was associated with increased gut diversity and decreased levels of key intestinal taxa commonly considered pathobionts, including Klebsiella spp., Escherichia spp., Shigella spp., and Klebsiella pneumoniae . At the phylum level, fecal Bacteroidota increased, while Mucoromycota decreased following treatment. Post-FMT nasal microbiome changes included reduced richness and diversity, expansion of Moraxella , and decreases in taxa linked with respiratory colonization, including Staphylococcus aureus and Streptococcus pneumoniae . By Day 56, nasal communities partially recovered toward healthy profiles. Baseline nasal ARG abundance decreased following FMT, particularly among β-lactam, aminoglycoside, and fluoroquinolone resistance genes, and remained comparable to healthy controls by Day 56. In contrast, the oral microbiome and oral resistome remained largely stable, with only minor fluctuations, and no consistent increases in respiratory pathobiont-associated taxa. In summary, FMT was associated with broader effects beyond the gut, including changes in the URT microbial ecology and antimicrobial resistance profiles. Together, these findings are consistent evidence of gut-lung microbial interactions, linking intestinal dynamics with respiratory microbial composition and antimicrobial resistance patterns.