Cross-organ microbes modulate host upper gastrointestinal health and disease via the oral-gastric microbiome axis.

The human body harbors highly diverse and complex microbial communities across various regions. Among these, the oral cavity and stomach are directly connected and engage in dynamic microbial interactions. Microorganisms capable of migrating between these two distinct niches are referred to as trans-organ microbes, which constitute a core component of the oral-gastric microbiome axis. In this review, we elucidate the mechanisms underlying microbial translocation along the oral-gastric axis. We further discuss how these cross-organ microbes exert bidirectional influences on health and disease in upper gastrointestinal environments. They contribute to mucosal homeostasis and modulate immune responses, yet under certain conditions, they can also promote pathologies such as gastritis, gastric cancer, and oral disorders. The migration and colonization patterns of microbes across organs also hold potential for developing diagnostic biomarkers, as well as for designing innovative microbiome-based interventions targeting the upper gastrointestinal tract. In summary, this review highlights the oral-gastric microbiome axis as a critical frontier for understanding and manipulating microbiome dynamics in human health and disease.