Strain transmission links human microbiomes along the oral-gut axis and across cohabiting individuals.

Interpersonal strain transmission shapes the human microbiome, yet a comparative understanding of the transmission dynamics across body sites is lacking. We analyzed 1,644 paired oral and fecal metagenomes to investigate microbiome transmission among healthy cohabitants and intra-individual oral-gut overlap. Cohabitants shared significantly more oral and gut strains than non-cohabitants. Romantic partners exhibited the highest oral strain-sharing rates, exceeding their gut strain sharing. Higher oral transmissibility was associated with increased longitudinal strain replacement, while the most transmissible gut species were linked to poorer cardiometabolic health. Within individuals, 74.5% of cases of species detected in both sites involved the same strains, primarily related to abundant oral species such as Streptococcus salivarius, suggesting saliva-mediated transmission. Conversely, Bifidobacterium longum strains never overlapped between sites, with the recently proposed B. longum subsp. nexti uniquely colonizing the oral cavity. These findings extend our understanding of microbiome spread and its potential consequences for human health.