The gut-brain axis has been increasingly implicated in neuroscience research in the last decade. The findings from observational and interventional studies have shown that changes in the diversity of the gut microbiome affect pathological and behavioral symptoms of neurodegenerative disorders. The gastrointestinal tract harbors trillions of microorganisms, and the composition of gut microbiota is influenced by environmental factors and host genetics. The empirical experiments manipulating the diversity of gut microbiota have indicated that improving the immune function of the host from the gastrointestinal tract ameliorates the behavioral signs of neurodegenerative disorders. The importance of diet, chemical exposure, and infection for normal gastrointestinal function has been shown, and the diet has been heavily implicated in the manipulation of the microbiome diversity in both animal and human studies.
The gut-brain axis research is growing and increasingly dominating the literature of neurological disorders. The gut microbiome has been suggested as a triggering factor for neurodegenerative disorders. Disruptions in the gut microbiota diversity are associated with increased pro-inflammatory cytokine interleukin-1 beta (IL-1b) and tumor necrosis factor-alpha (TNF- α) levels in both animal and human models. However, it is not fully clear in humans whether the microbiome alterations impair the function of the neuroimmune system. The gut microbiota can regulate the myelin production in the prefrontal cortex, as evidenced in animal studies, and the diversity of gut microbiota is somehow correlated with the integrity of the blood-brain barrier.
Multiple sclerosis is mediated by the immune system; hence, the immune system-regulating factors such as the gut microbiota-derived products/metabolites have been mostly implicated in the pathogenesis of multiple sclerosis. The normal diversity of gut microbiota is important for social development, and colonizing the germ-free mice with the microbiome from autistic people is enough to induce the behavioral symptoms of autism in the transfected mice. Administration of anti-inflammatory bacteria, such as Bacteroides fragilis, and Lactobacillus reuteri, could improve the pathology of autism spectrum disorder.
Alzheimer's disease is a neurodegenerative disorder affecting more than 6 million Americans age 65. The gut-brain axis influences the main hallmarks of Alzheimer's disease. Disruptions in the gut microbiota diversity are associated with increased pro-inflammatory cytokine interleukin-1 beta (IL-1b) and tumor necrosis factor-alpha (TNF- α) levels. Rearing germ-free mice reduces pro-inflammatory cytokine IL-1b level, amyloid beta (Aβ) load, and the number of activated-microglia in the brain. Microbiome profiling in different mouse models of Alzheimer’s disease has indicated the alterations in gut microbiota. The other bacteria that show a reciprocal relationship with tau pathology are Butyricicoccus, Eubacterium xylanophilum, Candidatus saccharimonas, Paraprevotella, Odoribacter, Alistipes, Blautia, Rikenella, Ruminococcaceae, and Parvibacter; and the bacteria positively correlated with tau accumulation are Clostridium inoculum, Parabacteroides, Bacteroides, and Escherichia-Shigella.
Bacterial amyloid in the gastrointestinal tract increases the aggregation of alpha-synuclein in the brains of Caenorhabditis elegans and mice models. The interaction between bacterial amyloid and tau pathogenesis could provide an avenue for curli research in future therapeutic studies.
In conclusion, the gut-brain axis provides neuroscientists a direct intervention route to the function of the central nervous system. The diversity of gut microbiota is mediated by environmental factors, and how the gut microbiota products impact peripheral and central nervous systems are important questions that remain unanswered. Animal experiments have indicated that microbial changes are correlated with neuroinflammation, triggering neurodegenerative disorders as well as behavioral changes. Therefore, such a microbial-centric interventional strategy is worth considering in neurodegenerative disorders.
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