Streptococci, a versatile bacterial group, thrive in various host habitats. The intricate oral-gut axis, linking the oral cavity and gastrointestinal tract, plays a pivotal role in shaping microbial composition and host health. This dynamic interaction provides streptococci with opportunities for evolutionary adaptation. This study delves into the genetic changes and adaptive mechanisms exhibited by streptococci during colonization of both oral and intestinal habitats within the same individual.

We performed whole-genome sequencing on 218 streptococcal isolates from saliva and fecal samples of 14 Inflammatory Bowel Disease (IBD) patients and 12 healthy controls (HC). Analysis unveiled 16 distinct streptococcal species among the isolates, with S. infantis, S. mitis, S. parasanguinis, S. australis, and S. salivarius being the most predominant species. S. infantis dominated the oral habitat in both IBD patients and HC. It was the primary species in IBD fecal samples and the second most prevalent in those of HC. S. parasanguinis was more abundant in the gut of both groups than in their oral habitats. The analysis revealed within-host microevolution of different streptococcal species, with evidence of adaptations through recombination events and the acquisition of mobile genetic elements (MGEs). The tetA gene encoding tetracycline resistance was significantly more abundant in genomes of fecal origin. Streptococcal genomes with intestinal origin had a higher percentage of intact phage sequences compared to their oral counterparts. MGEs such as CRISPR-Cas and restriction modification systems had significant impact on niche-specific genotype diversities, facilitating streptococcal genome evolution through the integration of exogenous DNA. The core-genome single nucleotide polymorphisms (SNPs) analysis consistently demonstrated that oral and intestinal streptococcal genomes from the same individual exhibited distinct clustering, characterized by a significant number of core-SNPs differences. Our findings suggest emergence of distinct lineages within each habitat, and within-host streptococcal evolution is individual-dependent, potentially initiated in the oral cavity.