Microbiota–Gut–Brain Axis: Barrier Function and Lymphatic System in Neurological Health Original paper

What Was Reviewed?

This review explores the microbiota–gut–brain axis (MGBA), with a focus on the interplay between the gut microbiota, intestinal and blood-brain barrier integrity, and the lymphatic system. The authors examine how gut microbes influence barrier function through neural transmission, metabolite production, immune modulation, and gut hormone signaling. A significant aspect of the review is the role of lymphatic vessels as a previously underappreciated conduit between the gut and brain. The review also discusses the impact of microbiota dysbiosis on barrier dysfunction and its implications for both gastrointestinal and neurological diseases.

Who Was Reviewed?

The review synthesizes findings from various microbiome studies, including those investigating the microbiota’s role in intestinal permeability, neuroinflammation, and neurological conditions. It integrates evidence from experimental models and human studies to highlight key mechanisms underlying MGBA communication.

Key Findings and Microbiome Associations

The review underscores that the gut microbiota exerts a profound influence on both the intestinal and blood-brain barriers, modulating permeability and contributing to systemic homeostasis. Several key points emerge:

Microbiota and Barrier Function: Gut microbes regulate intestinal and blood-brain barrier integrity through microbial metabolites such as short-chain fatty acids (SCFAs), neurotransmitter production, and immune modulation. Butyrate, for example, strengthens the blood-brain barrier by enhancing tight junction protein expression.

Lymphatic System as a Communication Pathway: The lymphatic network, particularly intestinal lacteals, serves as a conduit for microbiota-derived molecules and immune cells, linking gut health with central nervous system (CNS) function. Dysregulation of lymphatic transport mechanisms is implicated in neurological disorders.

Gut Microbiota Dysbiosis and Neurological Conditions: Altered microbiota composition contributes to neuroinflammatory and neurodegenerative diseases. Increased gut permeability and translocation of microbial products, such as lipopolysaccharides (LPS), trigger systemic inflammation, which can exacerbate conditions like Alzheimer’s and Parkinson’s disease.

Vagus Nerve and Microbial Metabolites: The vagus nerve is a major conduit for gut-brain signaling. Microbial-derived neurotransmitters, including serotonin and dopamine precursors, influence neurological health. In animal models, vagotomy disrupts gut microbiota–mediated neurological effects, further supporting the role of direct neural communication.

Meningeal Lymphatics and CNS Immunity: The meningeal lymphatic system is increasingly recognized as an essential pathway for brain waste clearance and immune regulation. Dysfunction in these lymphatic vessels is linked to neuroinflammatory conditions such as multiple sclerosis and Alzheimer’s disease.

Implications of This Review

The findings emphasize the importance of maintaining gut microbiota balance to preserve barrier integrity and prevent systemic inflammation that may contribute to neurological diseases. This review suggests that therapeutic interventions targeting the microbiota—such as prebiotics, probiotics, fecal microbiota transplantation (FMT), and microbiota-modulating diets—could play a role in managing both gastrointestinal and neurodegenerative conditions. Additionally, interventions that enhance lymphatic function, such as VEGF-C-mediated lymphangiogenesis, have shown promise in mitigating neuroinflammatory disorders by regulating microbiota-host interactions.