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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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Cites
QIIME allows analysis of high-throughput community sequencing data
Caporaso, J. G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F. D., Costello, E. K., Fierer, N., Peña, A. G., Goodrich, J. K., Gordon, J. I., et al. (2010) · Nature Methods · doi:10.1038/nmeth.f.303 · Cited by 34,887
Search and clustering orders of magnitude faster than BLAST
Edgar, R. C. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq461 · Cited by 21,098
UCHIME improves sensitivity and speed of chimera detection
Edgar, R. C., Haas, B. J., Clemente, J. C., Quince, C., & Knight, R. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr381 · Cited by 15,114
Human gut microbes associated with obesity
Ley, R. E., Turnbaugh, P. J., Klein, S., & Gordon, J. I. (2006) · Nature · doi:10.1038/4441022a · Cited by 8,785
Enterotypes of the human gut microbiome
MetaHIT Consortium (additional members), Arumugam, M., Raes, J., Pelletier, E., Le Paslier, D., Yamada, T., Mende, D. R., Fernandes, G. R., Tap, J., Bruls, T., et al. (2011) · Nature · doi:10.1038/nature09944 · Cited by 7,548
Obesity alters gut microbial ecology
Ley, R. E., Bäckhed, F., Turnbaugh, P., Lozupone, C. A., Knight, R. D., & Gordon, J. I. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0504978102 · Cited by 6,176
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. (2013) · Nature · doi:10.1038/nature12721 · Cited by 5,549
Autophagy and Viruses: Adversaries or Allies?
Dong, X., & Levine, B. (2013) · Journal of Innate Immunity · doi:10.1159/000346388 · Cited by 4,444
Motor Neuron Degeneration in Mice that Express a Human Cu,Zn Superoxide Dismutase Mutation
Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., Caliendo, J., Hentati, A., Kwon, Y. W., Deng, H.-X., et al. (1994) · Science · doi:10.1126/science.8209258 · Cited by 4,143
Antimicrobial Autophagy: A Conserved Innate Immune Response in Drosophila
Moy, R. H., & Cherry, S. R. (2013) · Journal of Innate Immunity · doi:10.1159/000350326 · Cited by 3,551
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Items 101–200 of 291
Li, X., Dong, L., Li, A., Yi, J., Brotto, M., & Zhou, J. (2022) · Biomolecules · doi:10.3390/biom12020333 · Cited by 33
“Among those, butyrate has shown promising outcomes in alleviating disease progression in an ALS mouse model overexpressing the human ALS mutation SOD1G93A (G93A) [1,2].”
BackgroundSelf-citationUceda, S., Echeverry‐Alzate, V., Reiriz, M., Miguel, E. M., Pérez-Curiel, A., Gómez-Senent, S., & Beltrán-Velasco, A. I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713294 · Cited by 36
Zhang, L., Zhuang, Z., Zhang, G., Huang, T., & Fan, D. (2022) · BMC Neurology · doi:10.1186/s12883-021-02522-z · Cited by 31
“Observational studies have shown that the interface between the host and the gut microbiome may be altered in mouse models of ALS [9, 10], including impaired gut barrier function and a dysbiotic microbiome configuration that can be partially corrected by butyrate supplementation [10].”
BackgroundGut microbiome at the crossroad of genetic variants and behavior disorders
Cheng, L., Wu, H., Chen, Z., Hao, H., & Zheng, X. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2201156 · Cited by 29
Bonnechère, B., Amin, N., & van Duijn, C. M. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.831666 · Cited by 33
“Another main field of research is to determine if modification of the gut microbiota can decrease the risk of developing disease or improve the health of the patients: in Alzheimer’s disease (Mancuso and Santangelo, 2018), Parkinson’s disease (Sun and Shen, 2018), multiple sclerosis (Mirza and Mao-Draayer, 2017), amyo…”
BackgroundSun, Y., Li, X., & Bedlack, R. (2023) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2023.2174018 · Cited by 29
“In the G93A mSOD1 mouse model of ALS, PB mitigated histone hypoacetylation with a resultant delay in the onset of motor deficits, prolongation of survival, and improvement in motor function [9,10].”
BackgroundErber, A. C., Çetin, H., Berry, D., & Schernhammer, E. S. (2019) · International Journal of Neuroscience · doi:10.1080/00207454.2019.1702549 · Cited by 28
“[27] confirmed these findings in the same mouse model and showed that butyrate restored intestinal homeostasis, improved gut integrity and significantly decreased the level of abnormal Paneth cells, providing important first evidence for the therapeutic potential of butyrate in ALS.”
BackgroundResultGastrointestinal microbiota and inflammasomes interplay in health and disease: a gut feeling
Luca, R. D., Arrè, V., Nardone, S., Incerpi, S., Giannelli, G., Trivedi, P., Anastasiadou, E., & Negro, R. (2025) · Gut · doi:10.1136/gutjnl-2025-334938 · Cited by 33
“118 121 Recent research performed on animal models of PD, 122 AD 123 and MS 124 exhibited analogous outcomes.”
Casani-Cubel, J., Benlloch, M., Sanchis-Sanchis, C. E., Marín, R., Lajara-Romance, J. M., & Ortí, J. E. D. L. R. (2021) · Metabolites · doi:10.3390/metabo11020120 · Cited by 31
“This permeability is influenced by low levels of bacterial products as butyrate and SCFA, indeed, increasing these fatty acids results in intestinal integrity improvement, microbial homeostasis and extended life expectancy [53].”
BackgroundAmyotrophic Lateral Sclerosis: A Diet Review
D’Antona, S., Caramenti, M., Porro, D., Castiglioni, I., & Cava, C. (2021) · Foods · doi:10.3390/foods10123128 · Cited by 29
Mechanisms by which microbiome-derived metabolites exert their impacts on neurodegeneration
Kern, L., Mastandrea, I., Melekhova, A., & Elinav, E. (2024) · Cell chemical biology · doi:10.1016/j.chembiol.2024.08.014 · Cited by 27
Diet-microbiome-gut-brain nexus in acute and chronic brain injury
Krakovski, M., Arora, N., Jain, S., Glover, J., Dombrowski, K. E., Hernandez, B., Yadav, H., & Sarma, A. K. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1002266 · Cited by 27
“Attention on the effect of the microbiome on ALS disease progression and severity has been considered in animal and human models (Zhang et al., 2017).”
BackgroundGut-Modulating Agents and Amyotrophic Lateral Sclerosis: Current Evidence and Future Perspectives
Eddin, A. N., Alfuwais, M., Eddin, R. N., AlKattan, K. M., & Yaqinuddin, A. (2024) · Nutrients · doi:10.3390/nu16050590 · Cited by 32
“Other mechanisms by which dysbiosis may contribute to immune dysregulation in ALS include disabled autophagy and increased immune cell infiltration [77], although further investigation is warranted.”
BackgroundDeciphering internal and external factors influencing intestinal junctional complexes
Markovich, Z., Abreu, A., Sheng, Y., Han, S. M., & Xiao, R. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2389320 · Cited by 26
Cuffaro, F., Lamminpää, I., Niccolai, E., & Amedei, A. (2024) · Nutrients · doi:10.3390/nu17010102 · Cited by 25
“Butyrate also reduced abnormal Paneth cells and decreased the aggregation of the G93A SOD1 protein, suggesting it could be a promising treatment for ALS by addressing intestinal dysbiosis [188].”
Xin, Z., Xin, C., Huo, J., Liu, Q., Dong, H., Li, R., & Liu, Y. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-03988-x · Cited by 26
Brain–body mechanisms contribute to sexual dimorphism in amyotrophic lateral sclerosis
Jacob, S. M., Lee, S., Kim, S. H., Sharkey, K. A., Pfeffer, G., & Nguyen, M. D. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-00991-7 · Cited by 25
“Several studies have investigated connections between human ALS and the gut microbiota, with some promising early descriptive findings; modelling in mice is required to distinguish causality from correlative effects or bystander phenomena 71,255–260 .”
Haney, M. M., Ericsson, A. C., & Lever, T. E. (2018) · Comparative Medicine · doi:10.30802/aalas-cm-18-000039 · Cited by 23
Gut-Brain Axis Deregulation and Its Possible Contribution to Neurodegenerative Disorders
Villavicencio-Tejo, F., Olesen, M. A., Navarro, L., Calisto, N., Iribarren, C., GARCÍA, K. P., Corsini, G., & Quintanilla, R. A. (2023) · Neurotoxicity Research · doi:10.1007/s12640-023-00681-0 · Cited by 24
“Nowadays, studies continue searching for possible risk and therapeutic factors in ALS in which gut microbiota is suggested to have an impact (Wu et al. 2015; Gioia et al. 2020; Zhang, et al. 2017).”
Gut Symptoms, Gut Dysbiosis and Gut-Derived Toxins in ALS
Lee, A., Henderson, R. D., Aylward, J., & McCombe, P. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25031871 · Cited by 25
“There are reports of gut dysbiosis in ALS [15,21–23]; however, the studies carried out to characterize gut microbiota alterations have given contrasting results, likely due to differences in study design, including small sample sizes, lack of age and sex matching of control groups and different…”
BackgroundResultThe gut microbiome: an important role in neurodegenerative diseases and their therapeutic advances
Li, S., Zhao, L., Xiao, J., Guo, Y., Fu, R., Zhang, Y., & Xu, S. (2023) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-023-04853-6 · Cited by 23
“…mice, a mouse model of ALS, showed that supplementary butyrate significantly reduced abnormal Pan cells in G93A mice, reduced SOD1 G93A protein aggregation in the intestine, restored intestinal microbial homeostasis, improved intestinal integrity, and extended the lifespan of ALS mice [93].”
Self-citationCurrent potential therapeutics of amyotrophic lateral sclerosis
Lu, L., Deng, Y., & Xu, R. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1402962 · Cited by 26
“In animal experiments, PB alleviated histone hypoacetylation, leading to a delay in the development of motor deficits, an extension of survival time, and the enhancements of motor function (23, 24).”
BackgroundEffect of Short Chain Fatty Acids on Age-Related Disorders
Fernandes, M. F., de Oliveira, S., Portovedo, M., Rodrigues, P. B., & Vinolo, M. A. R. (2020) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-42667-5_4 · Cited by 22
Balakrishnan, R., Kang, S.-I., Lee, J. Y., Rho, Y., Kim, B.-K., & Choi, D. (2024) · Aging and Disease · doi:10.14336/ad.2024.1362 · Cited by 22
“Additionally, providing 2% butyrate in drinking water to an ALS mouse model enhanced gut integrity and survival [163].”
Fournier, C. N., Houser, M. C., Tansey, M. G., Glass, J. D., & Hertzberg, V. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.10.007 · Cited by 21
A network biology approach to unraveling inherited axonopathies
Bis‐Brewer, D. M., Danzi, M. C., Wuchty, S., & Zuchner, S. L. (2019) · Scientific Reports · doi:10.1038/s41598-018-37119-z · Cited by 19
The Gut Brain-Axis in Neurological Diseases
Barbosa, P., & Barbosa, E. R. (2020) · International Journal of Cardiovascular Sciences · doi:10.36660/ijcs.20200039 · Cited by 20
Target Metabolites to Slow Down Progression of Amyotrophic Lateral Sclerosis in Mice
Ogbu, D., Zhang, Y., Claud, K., Xia, Y., & Sun, J. (2022) · Metabolites · doi:10.3390/metabo12121253 · Cited by 20
“Furthermore, we reported that the bacterial metabolite butyrate reduced dysbiosis and restored functions of the intestinal barrier and enteric neurons in the SOD1G93A model [4,5].”
BackgroundInfluentialSelf-citationPeng, Z., Hou, T., Yang, K., Zhang, J., Mao, Y.-H., & Hou, X. (2025) · Nutrients · doi:10.3390/nu17111769 · Cited by 21
Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19
Zhang, J., Zhang, Y., Xia, Y., & Sun, J. (2023) · Genes & Diseases · doi:10.1016/j.gendis.2023.03.034 · Cited by 19
“Butyrate, a molecule found to benefit many diseases, 32,83,84 may be considered one of the potential treatments for long COVID.”
Self-citationSun, J., Ludvigsson, J. F., Roelstraete, B., Yudi Pawitan, Y., & Fang, F. (2021) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2021.1883666 · Cited by 17
Self-citationPsychobiotic Properties of Lactiplantibacillus plantarum in Neurodegenerative Diseases
Chiano, M. D., Sallustio, F., Fiocco, D., Rocchetti, M. T., Spano, G., Pontrelli, P., Moschetta, A., Gesualdo, L., Gadaleta, R. M., & Gallone, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179489 · Cited by 22
“Also, feeding these mice with butyrate improves the intestinal barrier integrity and GM homeostasis, prolonging lifespan [184].”
BackgroundShort-chain fatty acids in the context of Parkinson’s disease
Metzdorf, J., & Tönges, L. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.308089 · Cited by 18
More than just a number: the gut microbiota and brain function across the extremes of life
Nuzum, N. D., Deady, C., Kittel‐Schneider, S., Cryan, J. F., O’Mahony, S. M., & Clarke, G. A. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2418988 · Cited by 22
Relationship between Dietary Fiber Intake and the Prognosis of Amytrophic Lateral Sclerosis in Korea
Yu, H., Kim, S. H., Noh, M., Lee, S.-G., & Park, Y. (2020) · Nutrients · doi:10.3390/nu12113420 · Cited by 18
Parra‐Cantu, C., Zaldivar-Ruenes, A., Martinez-Vazquez, M. A., & Martínez, H. R. (2021) · Neurodegenerative Diseases · doi:10.1159/000517613 · Cited by 17
Microbiome and micronutrient in ALS: From novel mechanisms to new treatments
Sun, J., & Zhang, Y. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00441 · Cited by 20
Self-citationNayak, S. P. R. R., Das, A., Choi, K. C., Arasu, M. V., Namasivayam, S. K. R., Guru, A., & Arockiaraj, J. (2025) · Medicine in Microecology · doi:10.1016/j.medmic.2025.100133 · Cited by 17
Favero, F., Barberis, E., Gagliardi, M., Espinoza, S., Contu, L., Gustincich, S., Boccafoschi, F., Borsotti, C., Lim, D., Rubino, V., et al. (2022) · PLoS ONE · doi:10.1371/journal.pone.0273036 · Cited by 16
The Potential Role of Boron in the Modulation of Gut Microbiota Composition: An In Vivo Pilot Study
Sentürk, N. B., Kasapoğlu, B., Şahin, E., Özcan, O., Ozansoy, M., Ozansoy, M. B., Si̇yah, P., Sezerman, O. U., & Şahi̇n, F. (2024) · Pharmaceuticals · doi:10.3390/ph17101334 · Cited by 17
“It was discovered that treatment with probiotics such as Akkermansia muciniphila ameliorated the symptoms and provided positive results in the course of ALS in SOD1 transgenic mice [28,29].”
BackgroundAre There Modifiable Environmental Factors Related to Amyotrophic Lateral Sclerosis?
Kuraszkiewicz, B., Podsiadły-Marczykowska, T., Goszczyńska, H., & Piotrkiewicz, M. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00220 · Cited by 15
“Recent studies revealed signs of leaky intestine in G93A ALS mouse model (40, 41), which were associated with reduced levels of Butyrivibrio fibrisolvens, Escherichia coli, and Fermicus, as compared with wild-type mice.”
BackgroundAyala, V., Fontdevila, L., Rico-Rios, S., Povedano, M., Andrés‐Benito, P., Torres, P., Serrano, J. C. E., Pamplona, R., & Portero‐Otín, M. (2025) · Sclerosis · doi:10.3390/sclerosis3010008 · Cited by 15
“Addressing these limitations through future research is crucial for unlocking microbiota-targeted strategies to manage ALS more effectively.”
Ju, T., Zhang, Y., Liu, L., Zhao, X., Li, X., Liu, C., Sun, S., & Wu, L. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-24-01419 · Cited by 16
Self-citationThe microbiota-inflammasome-brain axis as a pathogenic mediator of neurodegenerative disorders
Sarkar, S. K., Gubert, C., & Hannan, A. J. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106276 · Cited by 15
“Treated mice also had a significant decrease in aberrant Paneth cells that govern host-bacterial communications in intestinal cells (Zhang et al., 2017).”
Lessons to Learn from the Gut Microbiota: A Focus on Amyotrophic Lateral Sclerosis
Calvo, A. C., Valledor-Martín, I., Moreno‐Martínez, L., Toivonen, J. M., & Osta, R. (2022) · Genes · doi:10.3390/genes13050865 · Cited by 15
“Interestingly, one published work in a SOD1G93A animal model [41] proposes that the population of Firmicutes bacteria is diminished before the onset of symptoms and possibly reflects a disease-stage-dependent (presymptomatic vs. symptomatic) modulation of microbiota in this model.”
BackgroundBacteria-Derived Protein Aggregates Contribute to the Disruption of Host Proteostasis
Walker, A. C., Bhargava, R., Dove, A. S., Brust, A. S., Owji, A. A., & Czyż, D. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094807 · Cited by 15
Watchon, M., Robinson, K. J., Luu, L., An, Y., Yuan, K. C., Plenderleith, S. K., Cheng, F., Don, E. K., Nicholson, G. A., Lee, A., et al. (2024) · The FASEB Journal · doi:10.1096/fj.202300963rr · Cited by 16
“These results indicate that sodium butyrate and butyric acid both warrant further investigation as autophagy-inducing agents with therapeutic potential for a wide range of neurodegenerative and protein aggregation diseases.”
ResultThe Current Potential Pathogenesis of Amyotrophic Lateral Sclerosis
Jiang, S., & Xu, R. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04269-3 · Cited by 16
Potential Preventive Strategies for Amyotrophic Lateral Sclerosis
Kuraszkiewicz, B., Goszczyńska, H., Podsiadły-Marczykowska, T., Piotrkiewicz, M., Andersen, P. M., Gromicho, M., Großkreutz, J., Kuźma‐Kozakiewicz, M., Petri, S., Stubendorff, B., et al. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00428 · Cited by 16
Intestinal Barrier Function and Neurodegenerative Disease
Wu, S., Yang, L., Fu, Y., Liao, Z., Cai, D., & Liu, Z. (2023) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/0118715273264097231116103948 · Cited by 13
Self-citationNiccolai, E., Martinelli, I., Quaranta, G., Nannini, G., Zucchi, E., Maio, F. D., Gianferrari, G., Bibbò, S., Cammarota, G., Mandrioli, J., et al. (2024) · Methods in molecular biology · doi:10.1007/978-1-0716-3662-6_27 · Cited by 15
Power and Sample Size Calculations for Microbiome Data
Xia, Y., Sun, J., & Chen, D. (2018) · ICSA book series in statistics · doi:10.1007/978-981-13-1534-3_5 · Cited by 13
Self-citationNon-Motor Symptoms of Amyotrophic Lateral Sclerosis: A Multi-Faceted Disorder
Nash, Y., & Sitty, M. (2021) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-210632 · Cited by 13
“In addition, this treatment also reduced SOD1 aggregation in the colon of mutant SOD1 mice [131].”
Mutant and curli-producing E. coli enhance the disease phenotype in a hSOD1-G93A mouse model of ALS
Kurlawala, Z., McMillan, J. D., Singhal, R. A., Morehouse, J. R., Burke, D. A., Sears, S. M., Duregon, E., Beverly, L. J., Siskind, L. J., & Friedland, R. P. (2023) · Scientific Reports · doi:10.1038/s41598-023-32594-5 · Cited by 12
Butyrate Feeding Reverses CypD-Related Mitoflash Phenotypes in Mouse Myofibers
Li, A., Li, X., Yi, J., Ma, J., & Zhou, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147412 · Cited by 12
“Our previous study show d butyr te feeding significantly alleviates the ALS disease progression of hSOD1G93A mice through improving gut integrity [45].”
BackgroundResultInfluentialSelf-citationBedlack, R., & ALSUntangled Group (2018) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2018.1440738 · Cited by 12
“Altering the fecal microbiome in the mutant SOD1 mouse model of ALS prolongs survival (60) and in a worm model of ALS improves motor function (61).”
BackgroundWhat do we know about the variability in survival of patients with amyotrophic lateral sclerosis?
McCombe, P., Garton, F. C., Katz, M., Wray, N. R., & Henderson, R. D. (2020) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2020.1785873 · Cited by 12
Microbiome and motor neuron diseases
Chatterjee, K., & Banerjee, S. (2020) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2020.08.010 · Cited by 12
Zhang, Y., Robinson, K., Xia, Y., & Sun, J. (2025) · Comprehensive physiology · doi:10.1002/cph4.70009 · Cited by 11
Self-citationSun, Y., Bedlack, R., Armon, C., Beauchamp, M. T., Bertorini, T. E., Bowser, R. P., Bromberg, M. B., Caress, J. B., Carter, G. L., Crayle, J. I., et al. (2022) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2022.2045323 · Cited by 11
“This group had a prolonged life span of 38 days (178 versus 140 days) (30).”
BackgroundExisting and Emerging Metabolomic Tools for ALS Research
Germeys, C., Vandoorne, T., Bercier, V., & Bosch, L. V. D. (2019) · Genes · doi:10.3390/genes10121011 · Cited by 12
Fang, X. (2018) · Metabolic Brain Disease · doi:10.1007/s11011-018-0239-x · Cited by 11
Quigley, S., Quigg, K. H., & Goutman, S. A. (2025) · CNS Drugs · doi:10.1007/s40263-025-01217-0 · Cited by 10
“Supplementation with butyrate improved survival time in an ALS mouse model [316].”
Mazzini, L., Marchi, F. D., Niccolai, E., Mandrioli, J., & Amedei, A. (2021) · Exon Publications eBooks · doi:10.36255/exonpublications.amyotrophiclateralsclerosis.microbiota.2021 · Cited by 10
“demonstrated that mice treated with butyrate restored intestinal microbial homeostasis and decelerated ALS progression (49).”
BackgroundYagi, A., & Yu, B. P. (2018) · Journal of Gastroenterology and Hepatology Research · doi:10.17554/j.issn.2224-3992.2018.07.762 · Cited by 10
Cross-talk between T-cells and gut-microbiota in neurodegenerative disorders
Pacheco, R. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.262582 · Cited by 10
“On the other hand, it has been demonstrated that the butyrate producing bacteria, Butyrivibrio Fibrisolvens, was selectively decreased in the intestinal microbiota of animals genetically susceptible to ALS, and the administration of butyrate significantly attenuated the disease development disease (Zhang et al., 2017).”
BackgroundTherapeutic Potential of Sodium Butyrate in Neurological and Psychiatric Disorders
Rahmani, D., Chodari, L., Kakallahpour, M., & Niknam, Z. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05428-w · Cited by 11
Shao, L., Liao, J., Qian, J., Chen, W., & Fan, X. (2021) · BMC Microbiology · doi:10.1186/s12866-021-02321-z · Cited by 9
Therapeutic potential of CBD in Autism Spectrum Disorder
Pedrazzi, J. F. C., Hassib, L., Ferreira, F. R., Hallak, J. E. C., Del-Bel, E., & Crippa, J. A. S. (2024) · International review of neurobiology · doi:10.1016/bs.irn.2024.05.002 · Cited by 12
The Microbiome in Neurodegenerative Disease
Brown, E. G., Tanner, C. M., & Goldman, S. M. (2018) · Current Geriatrics Reports · doi:10.1007/s13670-018-0240-6 · Cited by 10
Gut microbiota: the indispensable player in neurodegenerative diseases
Li, S., Cai, Y., Wang, S., Luo, L., Zhang, Y., Huang, K., & Guan, X. (2024) · Journal of the Science of Food and Agriculture · doi:10.1002/jsfa.13509 · Cited by 11
Self-citationXu, X., Wei, S., Lin, M., Chen, F., Zhang, X., & Zhu, Y. (2024) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2024.2440602 · Cited by 9
“Both in vitro and in vivo experiments indicated that ALS is related to the dysbiosis of butyrate-producing bacteria and butyrate, as butyrate treatment is linked to a decrease in SOD1 aggregation (Zhang et al. 2017).”
Nabakhteh, S., Lotfi, A., Afsartaha, A., Khodadadi, E. S., Abdolghaderi, S., Mohammadpour, M., Shokri, Y., Kiani, P., Ehtiati, S., Khakshournia, S., et al. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-04830-8 · Cited by 8
Oh my gut! Is the microbial origin of neurodegenerative diseases real?
Walker, A. C., & Czyż, D. M. (2023) · Infection and Immunity · doi:10.1128/iai.00437-22 · Cited by 11
“…cleaving enzyme 1; FAD, familial Alzheimer disease; N/A, not applicable; polyQ, polyglutamine; PS1, presenilin-1; TFAM, mitochondrial transcription factor A. "Worm" is used in place of Caenorhabditis elegans ; "Fly," Drosophila melanogaster ; "Mouse," Mus musculus ; and "Rat," Rattus norvegicus.”
Immune-microbiome interplay and its implications in neurodegenerative disorders
Uniyal, A., Tiwari, V., Rani, M., & Tiwari, V. (2021) · Metabolic Brain Disease · doi:10.1007/s11011-021-00807-3 · Cited by 9
“G93A mice which represents human ALS condition was observed to have an altered gut microbiome (Zhang et al. 2017).”
BackgroundExploring the role of gut microbiota in migraine risk: a two-sample Mendelian randomization study
Meng, X., Li, Q., Wang, D., Li, J., Cui, Y., Sun, Z., & Yin, H. (2023) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365521.2023.2298370 · Cited by 8
“For ALS, Zhang et al. first provided evidence of gut dysfunction and microbiome abnormalities as important components in ALS disease [14].”
BackgroundSun, J. (2017) · Journal of Neurology and Neuromedicine · doi:10.29245/2572.942x/2017/6.1136 · Cited by 8
Self-citationMicrobiota-Immune System Interactions in Human Neurological Disorders
Huang, Q., Fang, Y., Liao, D., & Xia, J. (2020) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527319666200726222138 · Cited by 7
Therapeutics Targeting Skeletal Muscle in Amyotrophic Lateral Sclerosis
Gao, J., Sterling, E., Hankin, R., Sikal, A., & Yao, Y. (2024) · Biomolecules · doi:10.3390/biom14070878 · Cited by 7
“Sodium butyrate has been shown to improve mitochondrial respiration and alleviate disease progression in ALS models [84–86].”
BackgroundChauhan, V., Chauhan, N. K., Dutta, S., Pathak, D., & Nongthomba, U. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1153422 · Cited by 8
“Moreover, it increased the lifespan of the mutant mice (Zhang et al., 2017).”
BackgroundMelnick, M., Gonzales, P. K., LaRocca, T. J., Song, Y., Wuu, J., Benatar, M. G., Oskarsson, B., Petrucelli, L., Dowell, R. D., Link, C. D., et al. (2021) · G3 Genes Genomes Genetics · doi:10.1093/g3journal/jkab141 · Cited by 8
Moțățăianu, A., Ion, V., Dumitreasă, M., Ormenișan, I., Farczádi, L., Andone, S. R., Bălașa, R., & Roman, M. (2025) · Biomolecules · doi:10.3390/biom15101380 · Cited by 7
“…models of Parkinson’s disease and brain injury, sodium butyrate increased occludin and zonula occludens-1 (ZO-1) expression in the hippocampus and frontal cortex, supporting BBB function [75,76], while supplementation with 2% butyrate in G93A mice restored gut integrity and extended lifespan [77].”
Butyrate extends health and lifespan in mice with mitochondrial deficiency
Gabandé‐Rodríguez, E., Heras, M. M. G. D. L., de Erenchun, P. R.-R., Simó, C., García‐Cañas, V., Inohara, N., Berenguer, I., Enriquez-Zarralanga, V., Fernández-Almeida, Á., Oller, J., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-70547-4 · Cited by 7
“We appreciate Reviewer 3 for their optimistic and constructive comments on our manuscript.”
Isacco, C. G., Ballini, A., Vito, D. D., Inchingolo, A. M., Cantore, S., Paduanelli, G., Nguyen, K. C. D., Inchingolo, A. D., Dipalma, G., & Inchingolo, F. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.88601 · Cited by 7
Myeloid vitamin D receptor regulates Paneth cells and microbial homeostasis
Bakke, D., Zhang, J., Zhang, Y., Ogbu, D., Xia, Y., & Sun, J. (2023) · The FASEB Journal · doi:10.1096/fj.202202169rr · Cited by 5
Self-citationGut Microbes: The Gut Brain Connection
Lynch, C. M. K., O’Riordan, K. J., Clarke, G. A., & Cryan, J. F. (2023) · Springer eBooks · doi:10.1007/978-3-031-46712-7_4 · Cited by 5
Koehn, L. M., Steele, J. R., Schittenhelm, R. B., Turner, B. J., & Nicolazzo, J. A. (2024) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.3c01089 · Cited by 5
Steenblock, D. A., Ikrar, T., San, A. A. S., Wardaningsih, E., & Azizi Masoud, J. (2018) · International Journal of Neurodegenerative Disorders · doi:10.23937/ijnd-2017/1710003 · Cited by 5
Ogbu, D., Zhang, Y., Claud, K., Xia, Y., & Sun, J. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.01.15.476456 · Cited by 5
Self-citationKiecka, A., & Szczepanik, M. (2025) · Pharmacological Reports · doi:10.1007/s43440-025-00800-y · Cited by 5
“A growing number of observational studies indicate that nutrients supplied to the body have a significant impact on the composition and function - ing of the gut microbiota, which in turn affects the overall condition of patients and the course of disease [ 38].”
Microbiome and metabolites impact enteric and central nervous systems in ALS
Walton, E. I., & Sun, J. (2026) · Gut Microbes · doi:10.1080/19490976.2026.2692737 · Cited by 4
Self-citationHu, Y., Chourpiliadis, C. P., Ingre, C., Ahlqvist, V. H., Sun, J., Song, H., Yudi Pawitan, Y., Piehl, F., & Fang, F. (2025) · Journal of Internal Medicine · doi:10.1111/joim.70008 · Cited by 3
Self-citationThe Gut-Brain Axis (GBA): Implications for Brain Longevity
Gautam, P., Vishwakarma, R. K., & Pathak, A. (2025) · Nutritional neurosciences · doi:10.1007/978-981-95-2790-8_9 · Cited by 4
Putative Anti-Cancer Action of Aloe vera Via Butyrate Fermentation
Yagi, A., & Yu, B. P. (2017) · Journal of Gastroenterology and Hepatology Research · doi:10.17554/j.issn.2224-3992.2017.06.738 · Cited by 4
Gut microbiota: Implications on human health and diseases
Farooqui, T. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821039-0.00009-5 · Cited by 4
Recent Insights on the Prospective role of Phytocompounds in Modulating Gut-Brain Axis
Kumari, N., Anand, S., Shah, K., & Chauhan, N. S. (2024) · Current Pharmacology Reports · doi:10.1007/s40495-024-00364-0 · Cited by 3
“For instance, the gut bacteria metabolise certain fla - vonoids, releasing active chemicals that are derived from the microbiome [62].”
Veyrat‐Durebex, C., Osman, S., Ojaimi, Y. A., Gosset, P., Dupuy, C., Lefèvre, A., Emond, P., Vourc’h, P., Corcia, P., Méreghetti, L., et al. (2024) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2024.2433578 · Cited by 3
The Role of the human microbiome in neurodegenerative diseases: A Perspective
Mukherjea, N., Khandelwal, A., Saluja, R., & Kalra, N. (2025) · Current Genetics · doi:10.1007/s00294-025-01319-8 · Cited by 3
“…- ing motor function animal and early human trials suggest that FMT and probiotics may improve motor function and reduce inflammation via immune modulation (Blacher et al. 2019 ; Zhang et al. 2017 ; Casani-Cubel et al. 2021 ; Mandri - oli et al. 2019; Cuffaro et al. 2024 ; Pascual et al. 2021).”
Yang, E. J. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26178419 · Cited by 5
“In ALS models, reduced butyrate-producing bacteria have been correlated with increased intestinal permeability, whereas butyrate treatment has been shown to enhance tight junction protein expression and delay disease onset [94].”
Banerjee, A., Goswami, A., & Choudhury, A. (2025) · BioNanoScience · doi:10.1007/s12668-025-02276-9 · Cited by 3
“In 8–12-month-old AD mice, there was a significant increase in Verrucomicrobia and Proteobacteria , and a decrease in Ruminococcus and Butyricicoccus compared to age-matched wild-type controls [ 230, 232].”
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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