Fecal microbiota transplantation significantly improved respiratory failure of amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive neurodegenerative disease leading to respiratory failure, eventually to death. However, effective treatments for ALS are lacking. Here we report the results of fecal microbiota transplantation (FMT) in two late-onset classic ALS patients with a Japan ALS severity classification of Grade 5, requiring tracheostomy and mechanical ventilation. In both patients, following two FMT procedures, significant improvements were observed in respiratory function, leading to the weaning off mechanical ventilation. Muscle strength improved, allowing for assisted standing and mobility. Other notable treatment responses included improved swallowing function and reduced muscle fasciculations. Metagenomic and metabolomic analysis revealed an increase in Bacteroides species (B. stercoris, B. uniformis, B. vulgatus), and Faecalibacterium prausnitzii after FMT, as well as elevated metabolites in arginine biosynthesis and decreased in branched-chain amino acid biosynthesis. These findings offer a potential rescue therapy for ALS with respiratory failure and new insights for the understanding of ALS.