Gut microbiome and amyotrophic lateral sclerosis: a systematic review of current evidence
Open accessAbstract
Amyotrophic lateral sclerosis (ALS), characterized by a loss of motor neurons in the brain and spinal cord, is a relatively rare but currently incurable neurodegenerative disease. The global incidence of ALS is estimated as 1.75 per 100,000 person‐years and the global prevalence is estimated as 4.1–8.4 per 100,000 individuals. Contributions from outside the central nervous system to the etiology of ALS have been increasingly recognized. Gut microbiome is one of the most quickly growing fields of research for ALS. In this article, we performed a comprehensive review of the results from existing animal and human studies, to provide an up‐to‐date summary of the current research on gut microbiome and ALS. In brief, we found relatively consistent results from animal studies, suggesting an altered gut microbiome composition in experimental ALS. Publication bias might however be a concern. Findings from human studies are largely inconclusive. A few animal and human studies demonstrated the usefulness of intervention with microbial‐derived metabolites in modulating the disease progression of ALS. We discussed potential methodological concerns in these studies, including study design, statistical power, handling process of biospecimens and sequencing data, as well as statistical methods and interpretation of results. Finally, we made a few proposals for continued microbiome research in ALS, with the aim to provide valid, reproducible, and translatable findings.
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In genetically mutated C9ORF72 mice, mutations in C9ORF72 cause infiltration of neutrophils and other immune cells and activation of microglia in the spinal cord.
“Studies of genetically mutated C9ORF72 mice have shown that mutations in C9ORF72 cause infiltration of neutrophils and other immune cells and activation of microglia in the spinal cord (79).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [79]
Intestinal biolysis and increased intestinal permeability have been observed in the SOD1G93A ALS mouse model.
“Intestinal biolysis and increased intestinal permeability have been observed in the SOD1G93A ALS mouse model (79).”
From Modulation of the gut–brain axis via the gut microbiota: a new era in treatment of amyotrophic lateral sclerosis (2023) · cites this paper as [79]
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Self-citationVariation in worldwide incidence of amyotrophic lateral sclerosis: a meta-analysis.
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2 of the 136 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
- Mariosa D, Kamel F, Bellocco R, Ye W, Fang F. Association between diabetes and amyotrophic lateral sclerosis in Swe- den. Eur J Neurol. 2015;22(11):1436-42.
- Chen X, Yazdani S, Piehl F, Magnusson PKE, Fang F. Poly- genic link between blood lipids and amyotrophic lateral scle- rosis. Neurobiol Aging. 2018;67:202.e1-202.e6.
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- Authors
- Sun, J., Huang, T., Debelius, J. W., & Fang, F.
- Affiliations
- Karolinska Institutet (SE)
- Corresponding author
- Fang, Fang
- Venue
- Journal of Internal Medicine
- Publisher
- Wiley
- Published
- 2021-07-08
- Volume
- 290
- Issue
- 4
- Pages
- 758-788
- ISSN
- 0954-6820 (ISSN-L)
- 1365-2796
- OpenAlex
- W3165351372
- Cited by
- 43
- References
- 136
- Citations by year
- 2026: 12 · 2025: 4 · 2024: 11 · 2023: 9 · 2022: 6 · 2021: 1
- FWCI
- 0.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Internal Medicine (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- European Research Council (802091)
- China Scholarship Council (201700260278)
- Karolinska Institutet
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- amyotrophic lateral sclerosis, gut microbiota, neurodegenerative diseases, microbial metabolites, animal models of ALS, human subjects research, publication bias, study design limitations
- MeSH terms
- Gastrointestinal Microbiome, Amyotrophic Lateral Sclerosis, Animals, Humans, Disease Progression
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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