The human microbiota encompasses diverse microbial communities inhabiting the gut, oral cavity, skin, respiratory tract, and urogenital system, each contributing uniquely to host physiology and health. While the gut microbiota has been extensively studied in the context of brain development and behavior through the microbiota-gut-brain axis, emerging evidence highlights that non-gut microbial ecosystems also shape neuroimmune processes and neurological outcomes. However, evidence supporting non-gut microbiota-brain interactions remains heterogeneous and is often indirect, with causal relationships largely unproven. A growing biological plausibility suggests that oral, skin, nasal, respiratory, and urogenital microbiota influence brain health through immune signaling, microbial metabolites, barrier integrity, and even direct neural pathways. This evidence is derived from a combination of human observational and epidemiological studies, complemented by mechanistic insights from animal models and in vitro systems. Microbial imbalance at these sites has been linked to neuroinflammation, neurodevelopmental alterations, and neurodegenerative diseases, although mechanistic insight remains limited. Moreover, cross-talk between different microbial niches may amplify or mitigate neurological effects, indicating the need for integrative, multi-site, and multi-omics approaches. By critically synthesizing evidence across multiple body sites, this mini-review highlights conceptual gaps, and the need to move beyond a gut-centric framework toward integrative, multisite investigations of microbiota-brain communication.
Gut-Brain Axis