The Microbiome-Brain Axis in Burning Mouth Syndrome and Its Comorbidities: An Integrated Perspective

Burning mouth syndrome (BMS) is a chronic nociplastic pain condition of unknown etiology, predominantly affecting women and highly comorbid with depression and anxiety. This narrative review proposes a comprehensive model integrating the significant role of the oral and intestinal microbiomes in BMS pathology. We explore how microbial dysbiosis compromises barrier functions, leading to systemic and neuroinflammation, and subsequently modulates key brain networks involved in pain processing and emotional regulation. Evidence suggests that dysbiosis within the oral microbiome (e.g., increased Streptococcus, Rothia, Bergeyella, Granulicatella, Neisseria) and/or the intestinal microbiome contributes to BMS pathology. This dysbiosis can compromise oral and intestinal barrier functions, leading to the systemic dissemination of bacterial components and inflammatory mediators. These factors induce neuroinflammation, which directly influences and dysregulates key brain networks such as the default mode network and salience network, crucial for pain processing and emotional regulation. The vagus nerve serves as a critical bidirectional communication pathway within this axis. Preliminary studies indicate potential therapeutic benefits of probiotics (e.g., Lactobacillus reuteri in BMS), but large-scale evidence is still emerging. The pathology of BMS, intertwined with depression and anxiety, can be significantly influenced by the oral and intestinal microbiomes. Dysbiosis contributes to chronic systemic and neuroinflammation, driving maladaptive changes in brain networks and neurotransmitter systems. While promising, the field is nascent, requiring further causal studies, detailed mechanistic insights, and robust clinical trials to establish the full therapeutic potential of microbiome-targeted interventions.