Gastrointestinal status and microbiota shaping in amyotrophic lateral sclerosis: A new frontier for targeting?

Abstract

Amyotrophic lateral sclerosis (ALS) is a rare and severe neurodegenera¬tive disease affecting the upper and lower motor neurons, causing diffuse muscle paralysis. Etiology and pathogenesis remain largely unclear, but several environ-mental, genetic, and molecular factors are thought to be involved in the disease process. Emerging data identify a relationship between gut microbiota dysbiosis and neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, and ALS. In these disorders, neuroinflammation is being increasingly recognized as a driver for disease onset and progression. Gut bacteria play a crucial role in maintaining and regulating the immune system, and changes in gut microbial composition can influence neural function by affecting neuro-immune interac¬tions, synaptic plasticity, myelination, and skeletal muscle function. This chapter outlines the relationship between ALS and the human microbiota, discussing whether an imbalance in intestinal microbiota composition through a pro-inflammatory dysbiosis promotes a systemic immune/inflammatory response, and has a role in ALS pathogenesis, clinical features, progression, and outcome.