Potential roles of gut microbiome and metabolites in modulating ALS in mice.
Level 5 - mechanism / opinion, no new human data
Preclinical animal model (Sod1-Tg mice) with small preliminary human case-control comparison
PubMed 31330533 · doi:10.1038/s41586-019-1443-5
What was done
Researchers evaluated gut microbiome and metabolite configurations in Sod1 transgenic (Sod1-Tg) ALS-prone mice under varying vivarium environments, germ-free conditions, and after broad-spectrum antibiotic treatment. They supplemented antibiotic-treated mice with specific commensal bacteria (including Akkermansia muciniphila, Ruminococcus torques, and Parabacteroides distasonis) and tested systemic nicotinamide supplementation on motor function and spinal cord gene expression. A small preliminary comparison of gut microbiomes and metabolite levels was also conducted between human ALS patients and household controls.
What was found
Sod1-Tg mice exhibited pre-symptomatic dysbiosis and altered metabolites, with worse disease under germ-free or antibiotic-treated conditions. Eleven commensal bacteria correlated with disease severity. Akkermansia muciniphila (AM) supplementation ameliorated ALS symptoms and increased central nervous system nicotinamide levels, whereas Ruminococcus torques and Parabacteroides distasonis worsened symptoms. Systemic nicotinamide improved motor symptoms and spinal cord gene expression in mice. Human ALS patients showed distinct microbiome configurations and reduced systemic and cerebrospinal fluid nicotinamide levels relative to household controls. No quantitative values or sample sizes were reported in the abstract.
Why it matters
This work suggests a functional gut-microbiome-brain axis in ALS progression, highlighting Akkermansia muciniphila and nicotinamide as potential metabolic targets for future human investigation.
Limits
The primary therapeutic and mechanistic findings derive from an animal model, which may not translate to human ALS pathophysiology. The human study was explicitly small and preliminary, exact numerical data and sample sizes are absent from the abstract, and causal mechanisms in humans remain unestablished.
Cited by
- contradicts A study found an association between high levels of Akkermansia muciniphila in the gut and amyotrophic lateral sclerosis (ALS).