Brain-Gut-Microbiota Axis in Amyotrophic Lateral Sclerosis: A Historical Overview and Future Directions
- Lizheng Xie, Li Pan, Baiyun Liu, et al.
- 2024
Why this matters for your gut health
This research directly informs us how the gut microbiota communicates with the brain to influence serious neurological disease. Gut bacteria and their metabolites — especially short-chain fatty acids (SCFAs) and compounds like TMAO — travel through the blood and affect the central nervous system. Disrupted gut bacteria appear to contribute to the onset and progression of ALS, and restoring gut balance through probiotics, prebiotics, or fecal transplantation may slow disease progression and extend survival.
Summary
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease in which the gut microbiome plays a previously underappreciated role. The gut and brain are in constant two-way communication through neural, immune, and endocrine pathways — collectively called the brain-gut-microbiota axis. Emerging evidence shows that ALS patients have a distinctly disrupted gut microbiome, particularly a loss of butyrate-producing bacteria. In turn, ALS disease progression further worsens microbial imbalance, creating a vicious cycle. Therapies targeting the gut — including probiotics, prebiotics, synbiotics, and fecal microbiota transplantation — show early promise in animal models, though human clinical evidence is still developing.
Key findings
- ALS patients consistently show reduced abundance of butyrate-producing bacteria (Roseburia intestinalis, Eubacterium rectale, Faecalibacterium, Lachnospiraceae), which are critical for gut barrier integrity and anti-inflammatory signalling.
- The ratio of Firmicutes to Bacteroidetes is commonly altered in ALS patients, reflecting broad microbial imbalance.
- Gut-derived LPS is significantly elevated in ALS patients’ plasma, activating peripheral immune cells and triggering neuroinflammation — even without active infection.
- Intestinal barrier dysfunction (leaky gut) occurs before motor neuron degeneration in animal models, suggesting gut damage may precede neurological symptoms.
- The gut metabolite TMAO activates the NLRP3 inflammasome, increasing inflammatory factors in the CNS, while SCFAs like butyrate have the opposite, neuroprotective effect.
- Colonisation of ALS mice with Akkermansia muciniphila raised nicotinamide levels in cerebrospinal fluid, improved movement, and extended survival.
- Blood-brain and blood-spinal cord barrier integrity are both compromised in ALS, allowing harmful gut-derived substances to enter the CNS.
Read the full paper
Citation
Chen S, Cai X, Lao L, Wang Y, Su H, Sun H. Brain-Gut-Microbiota Axis in Amyotrophic Lateral Sclerosis: A Historical Overview and Future Directions. Aging and Disease. 2024 Feb 1;15(1):74–95. doi: 10.14336/AD.2023.0524.