Role of Toll-Like Receptors and Oral-Gut-Brain Axis in Neurodegenerative and Neuropsychiatric Disorders Publisher



Sabouri E ; Shahmoradi T ; Keshvari N Z ; Khodaee P ; Saleki K ; Rezaei N
Source: Reviews in the Neurosciences Published:2026

Abstract

The oral-gut-brain axis is a path connecting the gastrointestinal tract and the central nervous system (CNS). The gut microbiota influences the immune system, metabolism, and nerve cells through the production of neurotransmitters and microbial metabolites that can cross the blood-brain barrier (BBB). The interplay between neuroinflammation and altered oral and gut microbiota is a bidirectional complex path modulated by inflammatory mediators. Recent studies suggest a potential role for Toll-like receptor (TLR) signaling pathways in the induction of neuroinflammation via the oral-gut-brain axis. As neuroinflammation is one of the key elements in the pathophysiology of neurodegenerative and neuropsychiatric disorders, this review was conducted to reflect on the pathophysiological pathways and clinical evidence on the role of TLR and inflammasome signaling pathways via oral-gut-brain axis in neurodegenerative diseases such as cognitive impairment, Alzheimer's disease, Multiple sclerosis, Parkinson's disease, Huntington's disease, and Amyotrophic lateral sclerosis, and psychiatric disorders such as major depressive disorder, anxiety disorders, schizophrenia, bipolar disorders, and Autism spectrum disorders. Because the contributing factors have not been fully understood yet, further studies could help provide novel therapeutic opportunities. © 2026 the author(s), published by De Gruyter, Berlin/Boston.