Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder marked by progressive motor neuron loss, muscle weakness, and respiratory failure, with current therapies offering limited benefit. Growing evidence implicates gut dysbiosis and disruption of the gut–brain axis (GBA) in ALS pathogenesis through mechanisms involving chronic inflammation, oxidative stress, and altered metabolic signaling. This review examines the evolving role of gut microbiota and fecal microbiota transplantation (FMT) in ALS, focusing on mechanistic pathways, clinical observations, safety considerations, and the potential for future therapeutic applications. The gut microbiota communicates with the central nervous system through the stimulation of the enteric nervous system, the production of neurotransmitters such as GABA, short-chain fatty acids, and serotonin, as well as microbial-associated molecular patterns that influence cytokine activity. ALS patients demonstrate reduced microbial diversity, diminished butyrate-producing bacteria, and enrichment of pro-inflammatory taxa. Preclinical studies and early clinical evidence suggest that FMT may help restore microbial balance, improve gastrointestinal symptoms, and modulate neuroinflammatory markers. Limited case reports and randomized trials have reported symptomatic benefits, including improved bowel function, mood, and quality of life; however, consistent disease-modifying effects remain unproven. Safety issues, particularly donor screening, adverse events, and regulatory concerns, require careful consideration. Overall, FMT represents a promising but experimental therapeutic strategy that may complement existing ALS treatments by targeting the gut–brain axis. Standardized, rigorous clinical trials are necessary to clarify its efficacy, refine treatment protocols, and establish long-term safety, ultimately determining its place in ALS management.
Varadharaj et al. (Mon,) studied this question.