infection on European farms is associated with an altered tonsil microbiome and resistome.

is a Gram-positive opportunistic pathogen causing systemic disease in piglets around weaning age. The factors predisposing to disease are not known. We hypothesized that the tonsillar microbiota might influence disease risk via colonization resistance and/or co-infections. We conducted a cross-sectional case-control study within outbreak farms complemented by selective longitudinal sampling and comparison with control farms without disease occurrence. We found a small but significant difference in tonsil microbiota composition between case and control piglets (=45+45). Variants of putative commensal taxa, including , were reduced in abundance in case piglets compared to asymptomatic controls. Case piglets had higher relative abundances of , and uncultured and species. Piglets developing disease post-weaning had reduced alpha diversity pre-weaning. Despite case-control pairs receiving equal antimicrobial treatment, case piglets had a higher abundance of antimicrobial resistance genes conferring resistance to antimicrobial classes used to treat . This might be an adaption of disease-associated strains to frequent antimicrobial treatment.