Temporal evolution of the microbiome, immune system, and epigenome with disease progression in ALS mice
Open accessAbstract
Amyotrophic lateral sclerosis (ALS) is a terminal neurodegenerative disease. Genetic predisposition, epigenetic changes, aging, and accumulated life-long environmental exposures are known ALS risk factors. The complex and dynamic interplay between these pathological influences play a role in disease onset and progression. Recently, the gut microbiome has also been implicated in ALS development. Additionally, immune cell populations are differentially expanded and activated in ALS compared to healthy individuals. However, the temporal evolution of both the intestinal flora and the immune system relative to symptom onset in ALS is presently not fully understood. To better elucidate the timeline of the various potential pathological factors, we performed a longitudinal study to simultaneously assess the gut microbiome, immunophenotype, and changes in ileum and brain epigenetic marks relative to motor behavior and muscle atrophy in the mutant superoxide dismutase 1 (SOD1G93A) familial ALS mouse model. We identified alterations in the gut microbial environment early in the life of SOD1G93A animals followed by motor dysfunction and muscle atrophy, and immune cell expansion and activation, particularly in the spinal cord. Global brain cytosine hydroxymethylation was also altered in SOD1G93A animals at disease end-stage compared to control mice. Correlation analysis confirmed interrelationships with the microbiome and immune system. This study serves as a starting point to more deeply comprehend the influence of gut microorganisms and the immune system on ALS onset and progression. Greater insight may help pinpoint novel biomarkers and therapeutic interventions to improve diagnosis and treatment for ALS patients.
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Growing evidence has indicated alterations in the gut microbiome and impaired intestinal barrier integrity in both ALS patients and animal models.
“Nevertheless, growing evidence has indicated alterations in the gut microbiome and impaired intestinal barrier integrity in both ALS patients and animal models.221–225”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [224]
Alterations in the gut microbiome occur in SOD1G93A mice before the onset of motor dysfunction, muscle atrophy, and immune cell activation in the spinal cord.
“Alterations in the gut microbiome have been observed in SOD1G93A mice prior to the onset of motor dysfunction, muscle atrophy, and immune cell activation in the spinal cord.224”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [224]
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Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
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The gut microbiome: a key player in the complexity of amyotrophic lateral sclerosis (ALS)
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Aberrant enteric neuromuscular system and dysbiosis in amyotrophic lateral sclerosis
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A Gut Feeling in Amyotrophic Lateral Sclerosis: Microbiome of Mice and Men
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Gut microbiome and amyotrophic lateral sclerosis: a systematic review of current evidence
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- Authors
- Figueroa-Romero, C., Guo, K., Murdock, B. J., Paez-Colasante, X., Bassis, C. M., Mikhail, K. A., Raue, K. D., Evans, M. C., Taubman, G. F., McDermott, A. J., O'Brien, P. D., Savelieff, M. G., Hur, J., & Feldman, E. L.
- Affiliations
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA
- University of North Dakota (US)
- University of Michigan (US)
- University of Oxford (GB)
- Corresponding author
- Feldman, Eva L.
- ORCID
- Venue
- Disease Models & Mechanisms
- Publisher
- The Company of Biologists
- Published
- 2019-01-01
- Volume
- 13
- Issue
- 2
- ISSN
- 1754-8403 (ISSN-L)
- 1754-8411
- PMC
- PMC6906635
- OpenAlex
- W2980199089
- Cited by
- 94
- References
- 114
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 18 · 2023: 12 · 2022: 16 · 2021: 18 · 2020: 10 · 2019: 1
- FWCI
- 7.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Disease Models & Mechanisms (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Program for Neurology Research & Discovery
- A. Alfred Taubman Medical Research Institute
- National Institutes of Health (R21 NS102960)
- Target ALS (N021258-00)
- Sinai Medical Staff Foundation Neuroscience Scholar Fund
- Robert and Katherine Jacobs Environmental Health Initiative
- Microbiome Explorer Program
- The CReATe consortium
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- amyotrophic lateral sclerosis, gut microbiota, immune system, epigenome, SOD1 G93A mice, familial ALS, disease progression, motor impairment, muscle atrophy, ileum, biomarkers, neurodegeneration
- MeSH terms
- Gastrointestinal Microbiome, Superoxide Dismutase-1, Epigenome, Amyotrophic Lateral Sclerosis, Animals, Bacteria, Brain, Feces, Female, Immune System, Inflammation, Leukocytes, Male, Mice, Inbred C57BL, Mice, Transgenic, Phenotype, Phylogeny, Time Factors, Disease Progression, Myeloid Cells, 5-Methylcytosine
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.
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