Perspectives on Pathological Crosstalk between Malocclusion and Multi-organ Systems: The Hidden Face of an Iceberg

Malocclusion is a dental disorder that has often been overlooked in physiological studies. It is defined as any malrelationship of dental arches with or without aberration in the teeth developmental disorder, which alters functions like mastication, swallowing, speech, etc. Mounting evidence implies that malocclusion might be associated with adjacent and remote organ dysfunction, albeit the underlying mechanisms are obscure. However, to date, no review has unified the framework correlating malocclusion with oral (mastication, speech) and distant organ pathologies such as ocular, auditory, nasal, cerebral, respiratory, musculoskeletal, cardiovascular, blood-related, renal, and sexual physiologies. Therefore, this perspective provides the first integrated framework correlating malocclusion with multiorgan pathology and outlines a prioritized research agenda to investigate the causality. We have also documented the prevalence of malocclusion types in children as well as adolescents, which has been revealed in Africans, followed by Europeans, Americans, and Asians. Specifically, the impact of occlusal disharmony on brain activity could be attributed to rich neurological connections between the stomatognathic system (jaw, teeth, muscles, joints) and brain regions involved in sensory, autonomic, and emotional regulation. Consequently, chronic orofacial pain and dysfunction related to malocclusion can activate limbic and cortical pathways modulating systemic inflammatory responses and immune regulation, potentially influencing other organ systems through neuroimmune crosstalk and neurobiological circuits. Malocclusion-associated dysfunction might alter neural inputs affecting broader systemic control, thereby impacting bone metabolism, vascular tone, and inflammation. Taken together, we presented our perspective on emerging data implying the possible malocclusion-associated pathological complications. A detailed understanding of these intricate associations between malocclusion and multi-organ system pathologies will offer a new direction for comprehensive intervention strategies to reduce significant mortality and morbidity, resulting in improved quality of life.