Microbiota Dysbiosis in Amyotrophic Lateral Sclerosis: A Systematic Review of Human Studies

🎖️ Top 10% JournalNov 7, 2025Molecular neurobiology

Imbalance of Gut Bacteria in Amyotrophic Lateral Sclerosis: A Review of Human Studies

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Abstract

Eighteen eligible human studies were selected for a systematic review on gut microbiota dysbiosis in ALS.

Altered microbial diversity was reported in most studies, indicating potential disruptions in gut health among ALS patients.
Reduced levels of butyrate-producing bacteria, such as Faecalibacterium and Roseburia, were observed, along with increased pro-inflammatory bacteria like Escherichia coli and Bacteroides.
Disruptions in short-chain fatty acids, bile acids, and lipid metabolism were revealed through integrated microbiome-metabolome analyses, some correlating with ALS progression and cognitive impairment.
While some studies showed minimal or no differences, there is overall support for a connection between dysbiosis and ALS pathophysiology.
Probiotic trials have demonstrated limited efficacy, suggesting a need for more targeted, patient-specific interventions.
Variability in methodologies, small sample sizes, and limited longitudinal data hinder definitive conclusions about the role of gut microbiota in ALS.

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive motor neuron degeneration. Despite intensive research, its pathogenesis remains poorly understood. Recent insights suggest a pivotal role of the gut microbiota in modulating neuroinflammation and neurodegeneration via the gut-brain axis. This systematic review aims to synthesize clinical evidence on gut microbiota dysbiosis in ALS, exploring microbial and metabolic alterations and their associations with disease progression and severity. A comprehensive literature search was conducted across PubMed, Embase, Scopus, Web of Science, and other databases up to May 10, 2024, adhering to PRISMA 2020 guidelines. Eighteen eligible human studies were selected based on predefined inclusion criteria. Data on microbial diversity, taxonomic shifts, metabolite profiles, and clinical correlations were extracted and assessed using a modified Newcastle-Ottawa Scale. Most studies reported altered microbial diversity, reduced butyrate-producing bacteria (e.g., Faecalibacterium, Roseburia), and increased pro-inflammatory taxa (e.g., Escherichia coli, Bacteroides) in ALS. Integrated microbiome-metabolome analyses revealed disruptions in SCFAs, bile acids, and lipid metabolism, some correlating with ALSFRS-R scores and cognitive impairment. Although some studies showed minimal or no differences, the overall evidence supports a link between dysbiosis and ALS pathophysiology. Probiotic trials demonstrated limited efficacy, highlighting the need for targeted, patient-specific interventions. Gut microbiota dysbiosis is increasingly recognized as a contributor to ALS progression. However, methodological variability, small sample sizes, and limited longitudinal data restrict definitive conclusions. Future research should employ standardized, multi-omics approaches and larger cohorts to clarify causal links and develop microbiome-informed diagnostics and therapies for ALS.

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