The DOI matches its Crossref record; 24 of the 25 references it cites were found in a registry or an index.
Gut inflammation and dysbiosis in human motor neuron disease
Open accessAbstract
Amyotrophic lateral sclerosis (ALS) is a systemic disorder that involves dysfunction of multiple organs. Growing evidence has shown that neurodegenerative disorders with gut dysbiosis affect the central nervous system via pro-inflammatory mediators thus impacting gut-brain communications. We have demonstrated dysbiosis and increased intestinal permeability in the SOD1G93A ALS mouse model. In this study, we comprehensively examined the human gut microbiome in stool samples and evaluated infection and markers of intestinal inflammation in five patients with ALS and motor neuron disorders. Five patients we studied all had alteration in their gut microbiome characterized by a low diversity of the microbiome, compared to healthy cohorts with relatively intact abundance. Firmicutes and Bacteroidetes are the two major members of bacteria at the phylum level. Low Ruminococcus spp. occurred in three patients with low Firmicutes/Bacteroidetes (F/B) ratio. A majority of patients had signs of intestinal inflammation. This is the first comprehensive examination of inflammatory markers in the stool of ALS patients. Studies in gut health and microbiome related to the onset and progression of ALS may reveal novel therapeutic targets for disease modulation.
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“Studies have found that, in ALS patients, gastrointestinal symptoms precede neurological symptoms in all cases (33); these include gastroesophageal reflux, chronic constipation, intermittent diarrhea, bloating, and abdominal pain.”
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 [33]
In the citing paper
“Blood endotoxin levels are elevated in ALS patients [10], possibly as a result of gut inflammation and microbiome changes [102].”
From The endotoxin hypothesis of neurodegeneration (2019) · cites this paper as [102]
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1 retracted
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“Probiotic supplements have been demonstrated their protective roles in anti-inflammation and restoring microbiome in various human diseases, including autoimmune diseases (de Oliveira et al. 2017) and multiple sclerosis (Kouchaki et al. 2017).”
BackgroundRetractedGut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease
Sampson, T. R., Debelius, J. W., Thron, T., Janssen, S., Shastri, G. G., Ilhan, Z. E., Challis, C., Schretter, C. E., Rocha, S., Gradinaru, V., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.018 · Cited by 3,622 · cited 5×
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“The complex interplay of gastrointestinal - central nervous system (CNS) communication involves autonomic and enteric nervous systems, neuroendocrine, and immune systems (Forsyth et al. 2011; Hsiao et al. 2013; Sampson et al. 2016).”
BackgroundForsyth, C. B., Shannon, K. M., Kordower, J. H., Voigt, R. M., Shaikh, M., Jaglin, J. A., Estes, J. D., Dodiya, H. B., & Keshavarzian, A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028032 · Cited by 974 · cited 2×
“The complex interplay of gastrointestinal - central nervous system (CNS) communication involves autonomic and enteric nervous systems, neuroendocrine, and immune systems (Forsyth et al. 2011; Hsiao et al. 2013; Sampson et al. 2016).”
BackgroundDysbiosis in inflammatory bowel disease
Tamboli, C. P., Neut, C., Desreumaux, P., & Colombel, J. F. (2004) · Gut · doi:10.1136/gut.53.1.1 · Cited by 743
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BackgroundGut Microbiota Diversity and Human Diseases: Should We Reintroduce Key Predators in Our Ecosystem?
Mosca, A., Leclerc, M., & Hugot, J. P. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.00455 · Cited by 612 · cited 2×
“Dysbiosis (e.g., loss of microbial diversity in the gut microbiota) are correlated with intestinal inflammation and change in intestinal integrity (Sun and Chang 2014; Mosca et al. 2016).”
BackgroundIntestinal epithelial vitamin D receptor deletion leads to defective autophagy in colitis
Wu, S., Zhang, Y., Lu, R., Xia, Y., Zhou, D., Petrof, E. O., Claud, E. C., Chen, D., Chang, E. B., Carmeliet, G., et al. (2014) · Gut · doi:10.1136/gutjnl-2014-307436 · Cited by 353 · cited 4×
“We have demonstrated increased serum IL-17 in the SOD1G93A ALS mice, compared to the wild-type mice (Wu et al. 2015a).”
BackgroundInfluentialSelf-citationA role for the gut microbiota in IBS
Collins, S. M. (2014) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2014.40 · Cited by 351 · cited 5×
“Changes in the ratio of F/B ratio correlate with various human gut disorders, like irritable bowel syndrome (Collins 2014) and inflammatory bowel diseases (Tamboli et al. 2004) and with certain central nervous system disorders like Parkinson’s disease (Sampson et al. 2016).”
BackgroundMethodInfluentialIntestinal dysbiosis and probiotic applications in autoimmune diseases
de Oliveira, G. L. V., Leite, A. Z., Higuchi, B. S., Gonzaga, M. I., & Mariano, V. S. (2017) · Immunology · doi:10.1111/imm.12765 · Cited by 324 · cited 1×
“Probiotic supplements have been demonstrated their protective roles in anti-inflammation and restoring microbiome in various human diseases, including autoimmune diseases (de Oliveira et al. 2017) and multiple sclerosis (Kouchaki et al. 2017).”
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Flagged first, then by citations
1 of the 25 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Sun, 2015, Does the gut drive ALS progression?, Future Medicine., 5, 375
Cited by
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Items 201–223 of 223
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DALSO: domain ALS ontologyPreprint
Podsiadły-Marczykowska, T., Andersen, P. M., Gromicho, M., Großkreutz, J., Kuźma‐Kozakiewicz, M., Petri, S., Szacka, K., Uysal, H., de Carvalho, M. A., & Piotrkiewicz, M. (2024) · medRxiv · doi:10.1101/2024.06.01.24308128
“…or cancer (Freedman et al. 2013; Gibson et al. 2016), medical conditions such as leaky intestine (De Marchi et al. 2018; Kuraszkiewicz et al. 2018; Rowin et al. 2017; Wright et al. 2018), head and spine traumas or surgeries, electrical injuries (Berger et al. 2000; Chen et al. 2007; Das et al.…”
BackgroundRole of microbiome gut-brain axis in brain disorders
Parashar, S., Kapoor, D. U., Gautam, R. K., & Thakur, A. K. (2025) · Elsevier eBooks · doi:10.1016/b978-0-443-21680-0.00013-4
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
Niu, T., Wang, F., Li, R., Liu, Q., Feei, Z., Zhou, X., Liu, T., Lin, J., Zhu, J., Yin, S., et al. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5368698
Zvyagina, V., Kuriakose, A., Simó, I., Kam, J. Y., Chakraborty, P., Robinson, K. J., Potapenko, A., Watchon, M., Paulsen, I. T., Gamage, H. K. A. H., et al. (2025) · Neurobiology of Disease · doi:10.1016/j.nbd.2025.107121
The role of gut dysbiosis in the pathogenesis of neurodegenerative diseases
Roudenský, P. (2025) · Neurologie pro praxi · doi:10.36290/neu.2025.036
Naseri, K., Dabiri, H., Olfatifar, M., Shahrbaf, M. A., Yadegar, A., Soheilian‐Khorzoghi, M., Sadeghi, A., Saadati, S., Rostami-Nejad, M., Verma, A. K., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26561569
Dong, L., Li, X., Li, A., Yi, J., Vockery, Y., Chang, Y., Pan, Z., Brotto, M. A. P., & Zhou, J. (2026) · Biomolecules · doi:10.3390/biom16020253
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Wen-Ya, G. U. O., XIANG, S.-J., ZHANG, X.-L., Yao, L., & Li, Y. (2026) · Shengming kexue · doi:10.3724/cbls.2026011
Kudiersky, N., Barker, L. A., Dalton, C. F., Sharrack, B., Nair, K. S., Kesterton, S., & Carter, A. (2026) · Research Square · doi:10.21203/rs.3.rs-8086671/v1
Terrin, F., Faggin, S., Bizzotto, E., Santinello, D., Cerantola, S., Borsato, G., Fabris, F., Scarso, A., Licitra, R., Guella, G., et al. (2026) · Research Square · doi:10.21203/rs.3.rs-9163005/v1
The ‘gut feeling’: Connecting neurodegenerative diseases and gut microbiota
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ALS and the Microbiome: Understanding the Gut’s Impact on Motor Neuron Degeneration
Deepika, N. P., & Muhasina, K. M. (2026) · Springer eBooks · doi:10.1007/978-981-95-7494-0_5
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“The progressive compositional disruption observed from controls to ALS to PEG suggests a continuum of gut microbial deterioration, potentially exacerbated in PEG patients by enteral feeding and advanced disease (Rowin et al., 2017).”
Niu, T., Wang, F., Li, R., Liu, Q., Ma, Z., Zhou, X., Liu, T., Lin, J., Zhu, J., Yin, S., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-65659-2
Beyond the Ribosome: The Expanding Role of the Nucleolus in Neurodegenerative Pathways
Iacono, D., & Feltis, G. C. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-06146-7
“Alterations in the gut microbial composition have been documented in patients with Parkinson’s disease [158], Alzheimer’s disease [159], and ALS [160].”
Dresel, F. C., Michaelis, M., & Gourlay, C. W. (2026) · International Journal of Cell Biology · doi:10.1155/ijcb/3022967
“It has been reported that dysbiosis and decreased diversity of the microbiome compared with healthy controls is observed in ALS patients [30].”
Microbiome and Diseases: Gut–Brain Axis and Neurological Disorders
de Castilhos, J., & Stein‐Thoeringer, C. K. (2026) · Springer eBooks · doi:10.1007/978-3-032-26410-7_18
Jiahui, Z. H. O. U., Wang, J., Li, X., Dou, J., Chen, S., & Xue, F. (2026) · Life · doi:10.3390/life16111808
Metadata
- Authors
- Rowin, J., Xia, Y., Jung, B., & Sun, J.
- Affiliations
- Wellness and Integrative Neurology; Westchester Illinois
- University of Illinois Chicago (US)
- Corresponding author
- Sun, Jun
- Venue
- Physiological Reports
- Publisher
- Wiley
- Published
- 2017-09
- Volume
- 5
- Issue
- 18
- Pages
- e13443
- ISSN
- 2051-817X (ISSN-L)
- PMC
- PMC5617930
- OpenAlex
- W2759952551
- Cited by
- 224
- References
- 25
- Citations by year
- 2026: 23 · 2025: 21 · 2024: 32 · 2023: 22 · 2022: 29 · 2021: 38 · 2020: 25 · 2019: 20 · 2018: 13 · 2017: 1
- FWCI
- 6.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Physiological Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (R01 DK105118)
- 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, motor neuron disease, gut microbiota, dysbiosis, intestinal inflammation, intestinal permeability, gut-brain axis, Firmicutes/Bacteroidetes ratio, Ruminococcus, microbial diversity, SOD1 G93A mouse model
- MeSH terms
- Gastrointestinal Microbiome, Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis, Female, Humans, Male, Middle Aged, Inflammatory Bowel Diseases, Bacteroidetes, Ruminococcus, Dysbiosis
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