Regulation of common neurological disorders by gut microbial metabolites

초록

Neurological disorders: bugs that benefit the brain Disturbances of the microbial ecosystem in our gut create physiological disturbances that can accelerate the onset of neurological disease. The intestinal microbiome generates a diverse array of metabolites that can boost metabolic health, immune function, and other essential biological processes in the human host. Jeongho Park of Kangwon National University, Chuncheon, South Korea, and Chang Kim at the University of Michigan, Ann Arbor, USA, have reviewed research into how disruption of the healthy microbiome may contribute to Alzheimer's, Parkinson's, multiple sclerosis, and autism spectrum disorders. These studies indicate that such a "dysbiotic" state is generally associated with increased levels of inflammation. These disturbances are not sufficient to trigger neurological disorders on their own, but the resulting inflammatory state can act in concert with other biological risk factors to accelerate disease pathology. The gut is connected to the CNS by immunological mediators, lymphocytes, neurotransmitters, microbes and microbial metabolites. A mounting body of evidence indicates that the microbiome exerts significant effects on immune cells and CNS cells. These effects frequently result in the suppression or exacerbation of inflammatory responses, the latter of which can lead to severe tissue damage, altered synapse formation and disrupted maintenance of the CNS. Herein, we review recent progress in research on the microbial regulation of CNS diseases with a focus on major gut microbial metabolites, such as short-chain fatty acids, tryptophan metabolites, and secondary bile acids. Pathological changes in the CNS are associated with dysbiosis and altered levels of microbial metabolites, which can further exacerbate various neurological disorders. The cellular and molecular mechanisms by which these gut microbial metabolites regulate inflammatory diseases in the CNS are discussed. We highlight the similarities and differences in the impact on four major CNS diseases, i.e., multiple sclerosis, Parkinson's disease, Alzheimer's disease, and autism spectrum disorder, to identify common cellular and molecular networks governing the regulation of cellular constituents and pathogenesis in the CNS by microbial metabolites.

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