Temporal evolution of the microbiome, immune system and epigenome with disease progression in ALS mice
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 plays a role in disease...
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The Company of Biologists
2020-02-01
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| Series: | Disease Models & Mechanisms |
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| Online Access: | http://dmm.biologists.org/content/13/2/dmm041947 |
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doaj-64f5926e40e64b40a86f4cc580bd55d12020-11-25T01:12:54ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112020-02-0113210.1242/dmm.041947041947Temporal evolution of the microbiome, immune system and epigenome with disease progression in ALS miceClaudia Figueroa-Romero0Kai Guo1Benjamin J. Murdock2Ximena Paez-Colasante3Christine M. Bassis4Kristen A. Mikhail5Kristen D. Raue6Matthew C. Evans7Ghislaine F. Taubman8Andrew J. McDermott9Phillipe D. O'Brien10Masha G. Savelieff11Junguk Hur12Eva L. Feldman13 Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA Department of Pharmacology, University of Oxford, Oxford OX1 3QT, UK Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109, USA Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, USA Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA 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 plays a role in disease onset and progression. Recently, the gut microbiome has also been implicated in ALS development. In addition, 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. This article has an associated First Person interview with the joint first authors of the paper.http://dmm.biologists.org/content/13/2/dmm041947amyotrophic lateral sclerosisg93agutneurodegenerationsod1immunophenotype |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Claudia Figueroa-Romero Kai Guo Benjamin J. Murdock Ximena Paez-Colasante Christine M. Bassis Kristen A. Mikhail Kristen D. Raue Matthew C. Evans Ghislaine F. Taubman Andrew J. McDermott Phillipe D. O'Brien Masha G. Savelieff Junguk Hur Eva L. Feldman |
| spellingShingle |
Claudia Figueroa-Romero Kai Guo Benjamin J. Murdock Ximena Paez-Colasante Christine M. Bassis Kristen A. Mikhail Kristen D. Raue Matthew C. Evans Ghislaine F. Taubman Andrew J. McDermott Phillipe D. O'Brien Masha G. Savelieff Junguk Hur Eva L. Feldman Temporal evolution of the microbiome, immune system and epigenome with disease progression in ALS mice Disease Models & Mechanisms amyotrophic lateral sclerosis g93a gut neurodegeneration sod1 immunophenotype |
| author_facet |
Claudia Figueroa-Romero Kai Guo Benjamin J. Murdock Ximena Paez-Colasante Christine M. Bassis Kristen A. Mikhail Kristen D. Raue Matthew C. Evans Ghislaine F. Taubman Andrew J. McDermott Phillipe D. O'Brien Masha G. Savelieff Junguk Hur Eva L. Feldman |
| author_sort |
Claudia Figueroa-Romero |
| title |
Temporal evolution of the microbiome, immune system and epigenome with disease progression in ALS mice |
| title_short |
Temporal evolution of the microbiome, immune system and epigenome with disease progression in ALS mice |
| title_full |
Temporal evolution of the microbiome, immune system and epigenome with disease progression in ALS mice |
| title_fullStr |
Temporal evolution of the microbiome, immune system and epigenome with disease progression in ALS mice |
| title_full_unstemmed |
Temporal evolution of the microbiome, immune system and epigenome with disease progression in ALS mice |
| title_sort |
temporal evolution of the microbiome, immune system and epigenome with disease progression in als mice |
| publisher |
The Company of Biologists |
| series |
Disease Models & Mechanisms |
| issn |
1754-8403 1754-8411 |
| publishDate |
2020-02-01 |
| description |
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 plays a role in disease onset and progression. Recently, the gut microbiome has also been implicated in ALS development. In addition, 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. This article has an associated First Person interview with the joint first authors of the paper. |
| topic |
amyotrophic lateral sclerosis g93a gut neurodegeneration sod1 immunophenotype |
| url |
http://dmm.biologists.org/content/13/2/dmm041947 |
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