The human gut microbiota in people with amyotrophic lateral sclerosis
Open accessAbstract
Objective To characterize the gut microbiota in people with amyotrophic lateral sclerosis (ALS) relative to controls and to test the hypothesis that butyrate-producing bacteria are less abundant in the gastrointestinal tracts of people with ALS (PALS). Methods: We conducted a case–control study at Massachusetts General Hospital to compare the gut microbiota in people with ALS to that in controls. Metagenomic shotgun sequencing was performed on DNA extracted from stool samples of 66 people with ALS (PALS), 61 healthy controls (HC), and 12 neurodegenerative controls (NDC). Taxonomic metagenomic profiles were analyzed for shifts in the microbial community structure between the comparator groups using per-feature univariate and multivariate association tests. Results: The relative abundance of the dominant butyrate-producing bacteria Eubacterium rectale and Roseburia intestinalis was significantly lower in ALS patients compared to HC. Adjustment for age, sex, and constipation did not materially change the results. The total abundance of 8 dominant species capable of producing butyrate was also significantly lower in ALS compared to HC (p < 0.001). Conclusions: The levels of several butyrate-producing bacteria, which are important for gut integrity and regulation of inflammation, were lower in people with ALS compared to controls. These findings lend support to the inference that the gut microbiota could be a risk factor for ALS. Further investigations are warranted, preferably earlier in the disease with corresponding dietary collection and a longitudinal design.
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Reduced butyrate-producing species are identified in ALS patients and SOD1G93A mice.
“Furthermore, studies have identified reduced butyrate-producing species in ALS patients and SOD1G93A mice.221,222,345,346”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [345]
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Gut Microbes Associated with Neurodegenerative Disorders: A Comprehensive Review of the Literature
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Dysbiosis and Neurodegeneration in ALS: Unraveling the Gut–Brain Axis
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The microbiota-inflammasome-brain axis as a pathogenic mediator of neurodegenerative disorders
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Bacteria-Derived Protein Aggregates Contribute to the Disruption of Host Proteostasis
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Lessons to Learn from the Gut Microbiota: A Focus on Amyotrophic Lateral Sclerosis
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Gut Microbiota in Autophagy Regulation: New Therapeutic Perspective in Neurodegeneration
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Machado Joseph disease severity is linked with gut microbiota alterations in transgenic mice
Gamage, H. K. A. H., Robinson, K. J., Luu, L., Paulsen, I. T., & Laird, A. S. (2023) · Neurobiology of Disease · doi:10.1016/j.nbd.2023.106051 · Cited by 13 · see citing works
The Microbiome–Neurodegeneration Interface: Mechanisms, Evidence, and Future Directions
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Alterations in nasal microbiota of patients with amyotrophic lateral sclerosis
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Ageing, proteostasis, and the gut: Insights into neurological health and disease
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Faecal microbiota composition and impulsivity in a cohort of older adults with metabolic syndrome
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Microbiota Dysbiosis in Amyotrophic Lateral Sclerosis: A Systematic Review of Human Studies
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Anaerobes in specific infectious and noninfectious diseases: new developments
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Informatics for your Gut: at the Interface of Nutrition, the Microbiome, and Technology
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Roseburia intestinalis Modulates Immune Responses by Inducing M1 Macrophage Polarization
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Microbiome and metabolites impact enteric and central nervous systems in ALS
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Alteration of serum bile acids in amyotrophic lateral sclerosis
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Gut microbiota and ALS: cause, consequence or correlation? - a systematic review
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C9orf72 in myeloid cells prevents an inflammatory response to microbial glycogen
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The Microbiome Epoch: Cracking the Cardiovascular-Neurodegenerative Disorder Code
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The Role of Gut Microbiota-derived Short Chain Fatty Acids in Amyotrophic Lateral Sclerosis
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Neurodegenerative Diseases and the Gut Microbiota
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Human Microbiota Impact on the Efficacy of Pharmacological Treatments
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Update Review of the Relationship Between Gut Microbiota and Neurodegenerative Diseases
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Interplay Between Gut-microbiota and Neurodegeneration
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Human Microbiome and the Neurological Disorders
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Lima, R. S., Santos, R. S., Chaves‐Filho, A. B., Trzan, I. F. L., Inague, A., de Faria, R. L., Dantas, L. S., Pinto, I. F. D., de Medeiros, M. H. G., Steiner, A. A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.05.650333
- Authors
- Nicholson, K., Bjornevik, K., Abu-Ali, G., Chan, J., Cortese, M., Dedi, B., Jeon, M., Xavier, R., Huttenhower, C., Ascherio, A., & Berry, J. D.
- Affiliations
- Massachusetts General Hospital (US)
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Broad Institute (US)
- Harvard University (US)
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
- Publisher
- Informa UK Limited
- Published
- 2020-11-02
- Volume
- 22
- Issue
- 3-4
- Pages
- 186-194
- ISSN
- 2167-8421 (ISSN-L)
- 2167-9223
- OpenAlex
- W3096334056
- Cited by
- 123
- References
- 40
- Citations by year
- 2026: 19 · 2025: 23 · 2024: 28 · 2023: 20 · 2022: 24 · 2021: 8 · 2020: 1
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- ALS Finding a Cure
- Winthrop Family Fund in ALS Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- amyotrophic lateral sclerosis, gut microbiota, butyrate-producing bacteria, Eubacterium rectale, Roseburia intestinalis, microbial community structure, intestinal barrier integrity, inflammation, neurodegenerative diseases, risk factors, constipation
- MeSH terms
- Clostridiales, Eubacteriales, Gastrointestinal Microbiome, Amyotrophic Lateral Sclerosis, Humans, Case-Control Studies
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