Impact of the repurposed drug thonzonium bromide on host gastrointestinal microbiome. Microbiome from oral and gut rat samples

Animal models are key to understanding the impact of therapeutics on the resident microbiota and host tissues. However, microbiota changes at different body sites using rodent models remain underexplored due to cross-contamination associated with coprophagy. Here, we employed a host-infection rat model of dental caries using suspended cages to investigate the oral and gut microbiota from the same animals. We found distinctive site-specific microbiota that mirrors the human microbiome profile. Then, we assessed the impact of topical oral applications of a repurposed FDA-approved-drug, thonzonium bromide, on the gastrointestinal microbiome, and caries disease onset. Oral microbiota was perturbed by the treatments with specific disruption of Rothia and Veillonella, whereas no impact in the fecal microbial community was observed. The niche-specific disturbances in the oral cavity were also identified using computational and machine-learning models. Furthermore, host-tissue analyses revealed caries reduction on teeth without affecting the oral and gut soft tissues. Our data suggest localized oral disturbances by the repurposed-drug treatment exerted therapeutic effects without inflicting changes to the distant microbiome. Altogether highlighting the feasibility of in vivo models for host and microbiota analyses across the gastrointestinal tract.