The bacterium Streptococcus suis is a common colonizer in the oral cavity of pigs, and one of the major causes of infectious disease in piglets. Antibiotics are the main treatment against S. suis, and frequent usage selects for antibiotic resistance. Thus, it is important to develop alternative prevention strategies and treatments. This requires a better understanding of the factors predisposing to S. suis disease. This PhD thesis investigated associations between S. suis disease and the bacterial community colonizing the oral cavity of piglets. We discovered several bacteria that were increased or decreased in abundance in S. suis diseased piglets. S. suis was present at higher abundance prior to weaning than after, and it colonized healthy piglets in higher abundance than diseased ones. We also found that pathogenic variants occur at low abundance in the oral cavity of piglets and described how gene expression differs between S. suis clades.