Gut Microbiome and Microglial Interactions in Neurodegenerative Diseases

Abstract

The gut microbiome is a diverse ecosystem of trillions of microbes in the gastrointestinal tract. The microbiome has been an area of growing interest as new methods, such as sequencing and culturing techniques, have developed, shedding light on the extensive effects the gut microbiome has on various other body systems. This review focuses on the neurological system and the communication pathways between the gut and brain via the gut-brain axis. Because of the gut-brain axis, a healthy gut environment fosters increased healthiness of the brain, but when the microbiome is imbalanced - a condition called dysbiosis - brain health suffers. When dysbiosis occurs, several negative ramifications occur in various parts of the body. In the brain, microglia cells (innate immune response cells) can express a different phenotype and may be overactivated, resulting in the initiation of proinflammatory pathways. Inflammation in the brain, or neuroinflammation, is a characteristic of many neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. Complex interactions between the gut microbiome and microglia exist, including how gut-derived metabolites such as trimethylamine oxide and short-chain fatty acids increase microglial activation and neuroinflammation. However, therapeutic approaches targeting microglia and the gut-brain axis through tryptophan metabolites and bile salts mitigate neuroinflammation. Understanding these mechanisms opens potential avenues for reducing neuroinflammation and treating neurodegenerative diseases through the gut microbiome and microglia relationship.