Abstract
The oral-gut axis is a complex system linking the oral cavity and gastrointestinal tract, impacting host health and microbial composition. This study investigates genetic changes and adaptive mechanisms employed by streptococci-one of the few genera capable of colonizing oral and intestinal niches-within the same individual. We conducted whole-genome sequencing (WGS) on 218 streptococcal isolates from saliva and fecal samples of 14 inflammatory bowel disease (IBD) patients and 12 healthy controls. Our analysis identified 16 streptococcal species, with Streptococcus infantis, S. mitis, S. parasanguinis, S. australis, and S. salivarius being the most prevalent. S. infantis dominated the oral niche in both IBD patients (33%) and healthy controls (26%). It was also the primary species in fecal samples from IBD patients and the second most prevalent in those from healthy controls. S. parasanguinis was more prevalent in the gut than in the oral cavity in both groups. Comparative genomics demonstrated a within-host microevolution of streptococci, showing adaptations via recombination and acquisition of mobile genetic elements (MGEs). Intestinal streptococcal genomes exhibited a higher proportion of intact phages and a significantly greater acquisition of the tetA gene, which confers tetracycline resistance compared to oral genomes. Core-genome single-nucleotide polymorphisms (SNPs) analysis showed significant genetic divergence between oral and intestinal streptococcal genomes within the same individual. Our findings also unveil distinct niche-specific mutation signatures within intestinal genomes, indicating the emergence of distinct clonal lineages within each niche and suggesting that within-host streptococcal evolution is individual-dependent, initiated in the oral cavity.