A Role for the Lymphatic System in the Interactions Between Gut Microbiome and Brain
The gut microbiome changes with age in ways that increase inflammation and reduce the production of beneficial metabolites. Further, the balance of microbial populations is noted to tend towards distinct differences from the norm in patients with certain neurodegenerative conditions. A number of mechanisms by which the gut microbiome can influence the brain are well established, such as via production of butyrate, or the aforementioned increase in disruptive systemic inflammatory signaling. There are likely many more to be discovered as researchers continue to explore the fine details of aging throughout the body.
The human gastrointestinal (GI) tract contains trillions of microorganisms that exist symbiotically with the host due to a tolerant, regulatory cell- rich intestinal immune system. The microbiota-gut-brain axis (MGBA) refers to the interaction between host microbiome, the central nervous system (CNS), and the gastrointestinal tract. Barriers extending beyond the gut epithelial barrier, spanning the MGBA, are emerging as novel pathways facilitating communication between the gut microbiome and the brain. Disruption of the barrier integrity contributes a variety of gastrointestinal and neurological diseases. For decades, our understanding of barriers has shifted from perceiving them as rigidly impermeable cellular structures to dynamic and finely regulated communication interfaces with varying levels of permeability.
In this review, we explore barrier structure and function across the MGBA and examine the modulation of barrier function upon gut microbiota alteration. Additionally, we provide a summary of current knowledge concerning the lymphatic vasculature in the GI tract and CNS, highlighting its role in linking the reciprocal relationship between the lymphatic system and the microbiota, which collectively contributes to whole-body homeostasis. For decades, blood vessels and nerves were thought to be the primary pathways by which metabolites and toxins affect distant organs. It now appears that intestinal lymphatics constitute an additional pathway in the gut-organ axis. Numerous diseases are associated with deranged blood vessel endothelial barrier function, increased permeability, and extravasation into the microenvironment surrounding lymphatic vessels. It is conceivable that the microbiota might exert its effect on the initiation or progression of CNS disease through the lymphatic network in a direct or indirect manner.