The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Target Intestinal Microbiota to Alleviate Disease Progression in Amyotrophic Lateral Sclerosis
Open accessAbstract
Purpose Emerging evidence has demonstrated that gut microbiome plays essential roles in the pathogenesis of human diseases in distal organs. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Treatment with the only drug approved by the US Food and Drug Administration for use in ALS, riluzole, extends a patient׳s life span by only a few months. Thus, there is an urgent need to develop novel interventions that for alleviate disease progression and improve quality of life in patients with ALS. Here we present evidence that intestinal dysfunction and dysbiosis may actively contribute to ALS pathophysiology.Methods We used G93A transgenic mice as a model of human ALS. The G93A mice show abnormal intestinal microbiome and damaged tight junctions before ALS disease onset. The mice were given 2% butyrate, a natural bacterial product, in the drinking water.Results In mice fed with butyrate, intestinal microbial homeostasis was restored, gut integrity was improved, and life span was prolonged compared with those in control mice. At the cellular level, abnormal Paneth cells-specialized intestinal epithelial cells that regulate the host-bacterial interactions-were significantly decreased in the ALS mice treated with butyrate. In both ALS mice and intestinal epithelial cells cultured from humans, butyrate treatment was associated with decreased aggregation of the G93A superoxide dismutase 1 mutated protein.Implications The findings from this study highlight the complex role of the gut microbiome and intestinal epithelium in the progression of ALS and present butyrate as a potential therapeutic reagent for restoring ALS-related dysbiosis.
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“The administration of butyrate has been shown to increase the abundance of butyrate-producing Butyrivibrio fibrisolvens, restore Paneth cell homeostasis and enhance the intestinal barrier integrity of SOD1G93A mice.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [347]
In the citing paper
“Butyrate supplementation has demonstrated neuroprotective effects in SOD1G93A mice.222,347”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [347]
In the citing paper
“This is accompanied by reduced SOD1G93A aggregation in the intestine, thereby slowing disease progression and prolonging the lifespan of SOD1G93A mice.347”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [347]
In the citing paper
“Zhang et al. (72) found, using the 16sRDNA technique, that butyrate-producing bacteria (Butyrivibrio Fibrisolvens) were reduced in SOD1G93A mice, but after butyrate treatment, the mice exhibited restoration of homeostasis of the intestinal flora, restoration of intestinal epithelial barrier integrity, and improvement in clinical signs.”
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 [72]
In the citing paper
“Zhang et al. (72) found that treatment of ALS mice with oxalate extended their life span by an average of 38 days.”
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 [72]
In the citing paper
“Additionally, treatment of ALS mice with butyrate resulted in a significant decrease in the percentage of abnormal Paneth cells in the intestine. This treatment also restored the levels of lysozyme 1 and antimicrobial peptide defensin 5α in the intestine, as well as improving and slowing pathological progression of the intestine.”
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 [72]
In the citing paper
“This indicates the important role of butyrate in maintaining the physiological integrity of the intestine.”
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 [72]
In the citing paper
“This demonstrates the effectiveness of oxalate, a natural bacterial product, in restoring microbial and intestinal homeostasis.”
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 [72]
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Metadata
- Authors
- Zhang, Y.-G., Wu, S., Yi, J., Xia, Y., Jin, D., Zhou, J., & Sun, J.
- Affiliations
- Rush University Medical Center (US)
- Kansas City University (US)
- University of Illinois Chicago (US)
- Corresponding author
- Sun, Jun
- Venue
- Clinical Therapeutics
- Publisher
- Elsevier BV
- Published
- 2017-02
- Volume
- 39
- Issue
- 2
- Pages
- 322-336
- ISSN
- 0149-2918 (ISSN-L)
- PMC
- PMC5344195
- OpenAlex
- W2580573536
- Cited by
- 287
- References
- 49
- Citations by year
- 2026: 16 · 2025: 27 · 2024: 50 · 2023: 35 · 2022: 37 · 2021: 43 · 2020: 26 · 2019: 20 · 2018: 25 · 2017: 8
- FWCI
- 8.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK105118)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR057404)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- amyotrophic lateral sclerosis, gut microbiota, dysbiosis, butyrate, intestinal epithelium, Paneth cells, tight junctions, neurodegeneration
- MeSH terms
- Gastrointestinal Microbiome, Amyotrophic Lateral Sclerosis, Animals, Disease Models, Animal, Humans, Mice, Transgenic, Motor Neurons, Quality of Life, Superoxide Dismutase, Disease Progression, Mice
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