The Nasal Microbiota at the Brain-Immune Interface

Abstract

The nasal cavity serves as a critical interface between the external environment and the host and is anatomically connected to the brain through the olfactory and trigeminal nerves. In addition, the nasal mucosa is continuous with the gastrointestinal mucosa, thereby linking the nasal cavity with the gut. Despite its unique anatomical location, the physiological and pathological roles of the nasal microbiota remain much less understood than those of the gut microbiota. Since the launch of the Human Microbiome Project (HMP) by the National Institutes of Health in 2007, large-scale analyses have revealed that the human nasal microbiota differs substantially among anatomical regions and is highly influenced by multiple factors, including age, sex, and environmental conditions. Chronic rhinosinusitis (CRS) is associated with dysbiosis of both the nasal and gut microbiota, and these microbial alterations may further exacerbate chronic inflammation. Consequently, nasal microbiota transplantation has recently emerged as a novel therapeutic strategy for CRS. In addition, accumulating evidence suggests that nasal microbiota dysbiosis is associated with olfactory dysfunction and may contribute to the pathophysiology of a variety of neurological diseases, including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and depression. More recently, the nasal microbiota has been proposed to contribute to the development of dura-associated lymphoid tissue (DALT), suggesting that it may also influence neuroimmune function through the meningeal immune system. In this review, we summarize current knowledge of the nasal microbiota and discuss its interactions with the gut and the brain. We further propose a new conceptual framework, the “Microbiome-Nose-Meninges-Brain axis”, in which the nasal microbiota functions not merely as a local microbial community but as a key component of brain immunity at the brain-immune interface.