MICROBIOTA AND AMYOTROPHIC LATERAL SCLEROSIS: DYSBIOSIS, METABOLITES, AND EMERGING THERAPIES

Resumen

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by a short median life expectancy and significant phenotypic heterogeneity that cannot be fully explained by known genetic mutations, such as C9ORF72 and SOD1. Although the relevance of environmental risk factors is recognized, their precise relationship with the disease remains incompletely understood. The gut microbiome acts as a key regulator influencing both disease susceptibility and progression. Recent studies in murine models suggest that the gut microbiome may exert both protective and detrimental disease-modifying effects through the regulation of systemic inflammation and the production of bioactive metabolites. The bidirectional gut-brain axis plays a crucial role in this interaction, involving the intestinal barrier, the immune system, and the central nervous system (CNS). Modulation of the gut microbiota and investigation of the gut-brain axis represent one of the most promising areas of research for understanding the pathogenesis of ALS and other neurodegenerative diseases, offering new insights into how microbial composition influences neurodegeneration.