Potential roles of soy proteins, isoflavones, and exercise in modulating the oral microbiome–host axis in obesity and diabetes: microbial dysbiosis, inflammation, and immunometabolic signaling

Obesity and type 2 diabetes mellitus (T2DM) are complex metabolic disorders increasingly associated with alterations in the oral microbiome, chronic low-grade inflammation, dysregulated immunometabolic signaling, and systemic metabolic dysfunction. Although regular exercise is a cornerstone intervention for improving metabolic health, interindividual variability in exercise responsiveness has prompted interest in complementary nutritional strategies. Emerging evidence suggests that soy proteins and soy-derived isoflavones may influence metabolic and immune pathways relevant to exercise adaptation, potentially involving microbial and host-mediated mechanisms. This narrative review synthesizes current experimental and clinical evidence regarding the potential roles of soy proteins, isoflavones, and exercise in modulating the oral microbiome–host axis in obesity and diabetes. Particular attention is given to oral microbial dysbiosis, microbial metabolites, inflammatory and immune signaling, insulin resistance, glucose and lipid metabolism, vascular dysfunction, and systemic immunometabolic responses. We distinguish direct evidence from the oral microbiome from indirect evidence derived from the gut microbiome, systemic metabolic studies, and preclinical models. Although some findings suggest convergence of soy-derived bioactives and exercise on overlapping microbial and host pathways, such convergence should not be interpreted as experimentally established synergy. The potential contribution of microbial biotransformation of soy isoflavones and subsequent microbial–host interactions is also considered as an emerging, but incompletely characterized, mechanism linking dietary bioactives with systemic metabolic health. Overall, the available evidence supports a hypothesis-generating framework in which soy proteins, isoflavones, and exercise may contribute to complementary modulation of microbial ecology and host immunometabolic signaling; however, direct human evidence linking these interventions to oral microbiome changes remains extremely limited. Most mechanistic evidence derives from gut microbiome research, systemic metabolic outcomes, and preclinical models and therefore cannot be directly extrapolated to the oral microbiome–host axis. Further well-controlled human studies are needed to determine whether combined soy and exercise interventions can reproducibly modify oral microbial communities and whether such changes are associated with clinically meaningful metabolic outcomes in obesity and T2DM.