Translating microbial dysbiosis into brain health interventions: a focus on the oral-gut-reproductive inflammatory pathways.

Alterations in the microbial communities along the oral, gut, and reproductive (OGR) axis are increasingly recognized as major contributors to systemic inflammation, endocrine dysregulation, and neuroimmune pathophysiology. Scientific evidence has demonstrated that OGR dysbiosis is associated with neuroimmune signaling potentially by the leakage of lipopolysaccharides and cytokine cascades, with associated disruption of blood-brain barrier integrity, degeneration of the neurovascular unit, dysregulation of the hypothalamic-pituitary-adrenal axis, and disruption of neurotransmitter balance via abnormal tryptophan metabolism. The mechanisms have been implicated in the development of several neuropsychiatric and neurodegenerative disorders across preclinical and human observational models. Novel microbiome-targeted approaches, including antimicrobial therapy, prebiotics, probiotics, dietary modifications, and hormone-microbiota-targeting treatment, demonstrate potential to restore microbial balance and reduce neuroinflammation, with mechanistic effects on neurotransmitter production, barrier protection, and immune tolerance. However, these effects have been demonstrated predominantly in preclinical and animal models; robust evidence from well-powered human clinical trials is currently limited. Accordingly, these approaches should be considered exploratory and hypothesis-generating rather than established clinical strategies, and their translation to patient care requires rigorous evaluation in controlled human trials. This review addresses the gap in understanding how dysbiosis in these interdependent microbial ecosystems transmits inflammatory and metabolic signals that impair neurophysiology. This review presents a translational perspective on OGR-axis modulation as a frontier for the prevention and management of brain disorders, integrating microbial, immune, endocrine, and neural perspectives. Exploring these insights would birth a paradigm shift from symptom-management-based brain health interventions to microbiota-specific interventions.