The Microbiome as a Modifier of Neurodegenerative Disease Risk
Open accessAbstract
The gut microbiome is increasingly implicated in modifying susceptibility to and progression of neurodegenerative diseases (NDs). In this review, we discuss roles for the microbiome in aging and in NDs. In particular, we summarize findings from human studies on microbiome alterations in Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, and Huntington's disease. We assess animal studies of genetic and environmental models for NDs that investigate how manipulations of the microbiome causally impact the development of behavioral and neuropathological endophenotypes of disease. We additionally evaluate the likely immunological, neuronal, and metabolic mechanisms for how the gut microbiota may modulate risk for NDs. Finally, we speculate on cross-cutting features for microbial influences across multiple NDs and consider the potential for microbiome-targeted interventions for NDs.
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Gut micro-organisms are crucial for nervous system functions such as myelination, neurogenesis, microglial activation, and modulating cognition and behavior; gut micro-organisms are also increasingly implicated in modifying susceptibility to and progression of neurodegenerative diseases, including PD.
“Gut micro-organisms are crucial for nervous system functions such as myelination, neurogenesis, microglial activation, and modulating cognition and behavior; gut micro-organisms are also increasingly implicated in modifying susceptibility to and progression of neurodegenerative diseases, including PD [90, 91].”
From The gut–brain axis in early Parkinson’s disease: from prodrome to prevention (2025) · cites this paper as [90]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredAltering the gut microbiota in animal models alters immune function, metabolic activity, and ultimately lifespan by mechanisms associated with the aging process.
“Fang et al. (25) found that altering the gut microbiota in animal models alters immune function, metabolic activity, and ultimately lifespan by mechanisms associated with the aging process, and that alterations to the gut microbiota may positively or negatively affect the neuropathology and clinical manifestations of disease.”
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 [25]
Autophagy breaks down invading pathogens, regulates pathogens, triggers the release of pro-inflammatory cytokines, and participates in antigen presentation and lymphocyte development.
“In addition, autophagy in turn breaks down invading pathogens, regulates pathogens, triggers the release of pro-inflammatory cytokines, and participates in antigen presentation and lymphocyte development (25).”
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 [25]
In a study of six ALS patients, fecal microbiota exhibited reduced Firmicutes/Bacteroidetes in proportion to an increase in the abundance of Dorea and a concomitant decrease in the abundance of Oscillibacter, Anaerostipes, and Lachnospiraceae.
“In a study of six ALS patients by Fang et al. (25), the fecal microbiota of ALS patients was noted to exhibit reduced Firmicutes/Bacteroidetes in proportion to an increase in the abundance of Dorea and a concomitant decrease in the abundance of Oscillibacter, Anaerostipes, and Lachnospiraceae.”
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 [25]
Neuroinflammation is associated with the progression of ALS, and the microbiota, as a modifier of neurodegenerative disease risk, is closely associated with the inflammatory immune response.
“Several studies have shown that neuroinflammation is associated with the progression of ALS and that the microbiota, as a modifier of neurodegenerative disease risk (25), is closely associated with the inflammatory immune response.”
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 [25]
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Nagpal, J. K., & Cryan, J. F. (2021) · Neuron · doi:10.1016/j.neuron.2021.09.036 · Cited by 107 · see citing works
Panax ginseng and aging related disorders: A systematic review
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Microbiota–brain axis: Context and causality
Cryan, J. F., & Mazmanian, S. K. (2022) · Science · doi:10.1126/science.abo4442 · Cited by 103 · see citing works
Chen, C., Wang, G., Li, D., & Zhang, F. (2025) · Molecular Biomedicine · doi:10.1186/s43556-025-00307-1 · Cited by 119 · see citing works
Mechanisms underlying HIV-associated cognitive impairment and emerging therapies for its management
Ellis, R. J., Marquine, M. J., Kaul, M., Fields, J. A., & Schlachetzki, J. C. M. (2023) · Nature Reviews Neurology · doi:10.1038/s41582-023-00879-y · Cited by 98 · see citing works
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Ma, Y., Li, X., Yu, J., & Wang, Y. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00404-1 · Cited by 87 · see citing works
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Mahbub, N. U., Islam, M. M., Hong, S., & Chung, H. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2024.1348279 · Cited by 88 · see citing works
Enteric Microbiota-Mediated Serotonergic Signaling in Pathogenesis of Irritable Bowel Syndrome
Mishima, Y., & Ishihara, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910235 · Cited by 77 · see citing works
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Immune mechanisms and shared immune targets in neurodegenerative diseases
Weiner, H. L. (2024) · Nature Reviews Neurology · doi:10.1038/s41582-024-01046-7 · Cited by 63 · see citing works
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Gut microbiota produces biofilm-associated amyloids with potential for neurodegeneration
Fernández-Calvet, A., Matilla-Cuenca, L., Izco, M., Navarro, S., Serrano, M., Ventura, S., Blesa, J., Herráiz, M., Alkorta‐Aranburu, G., Galera, S., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48309-x · Cited by 55 · see citing works
A Gut Feeling in Amyotrophic Lateral Sclerosis: Microbiome of Mice and Men
Martin, S., Battistini, C., & Sun, J. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.839526 · Cited by 54 · see citing works
Targeting gut microbiota to alleviate neuroinflammation in Alzheimer’s disease
Nguyen, V. T. T., & Endres, K. (2022) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2022.114418 · Cited by 52 · see citing works
Gut-brain axis and neurodegeneration: mechanisms and therapeutic potentials
Park, K. J., & Gao, Y. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1481390 · Cited by 60 · see citing works
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Gut microbial metabolism in Alzheimer's disease and related dementias
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Metagenomic analysis characterizes stage-specific gut microbiota in Alzheimer’s disease
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Gut microbiome and amyotrophic lateral sclerosis: a systematic review of current evidence
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Parabacteroides as a promising target for disease intervention: current stage and pending issues
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Links between Diet, Intestinal Anaerobes, Microbial Metabolites and Health
Duncan, S. H., Conti, E., Ricci, L., & Walker, A. W. (2023) · Biomedicines · doi:10.3390/biomedicines11051338 · Cited by 38 · see citing works
Infections and immunity: associations with obesity and related metabolic disorders
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The gut–brain axis in early Parkinson’s disease: from prodrome to prevention
Oliver, P. J., Civitelli, L., & Hu, M. T. (2025) · Journal of Neurology · doi:10.1007/s00415-025-13138-5 · Cited by 42 · see citing works
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PKM2-mediated neuronal hyperglycolysis enhances the risk of Parkinson's disease in diabetic rats
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What, When and How to Measure—Peripheral Biomarkers in Therapy of Huntington’s Disease
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Fecal Microbiota Transplantation Role in the Treatment of Alzheimer's Disease: A Systematic Review
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The effect of lactoferrin in aging: role and potential
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Microbiome-based therapeutics for Parkinson's disease
Hamilton, A. M., Krout, I. N., White, A. C., & Sampson, T. R. (2024) · Neurotherapeutics · doi:10.1016/j.neurot.2024.e00462 · Cited by 31 · see citing works
Unlocking the mind-gut connection: Impact of human microbiome on cognition
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Animal and Cellular Models of Alzheimer’s Disease: Progress, Promise, and Future Approaches
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Gut microbiota, pathogenic proteins and neurodegenerative diseases
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Study of the gut microbiome in Egyptian patients with Parkinson’s Disease
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The Parkinson’s disease drug entacapone disrupts gut microbiome homeostasis via iron sequestration
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Gut Microbiota Predicts Healthy Late-Life Aging in Male Mice
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Microbial amyloids in neurodegenerative amyloid diseases
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The connection between gut microbiota and its metabolites with neurodegenerative diseases in humans
Fabi, J. P. (2024) · Metabolic Brain Disease · doi:10.1007/s11011-024-01369-w · Cited by 25 · see citing works
Blood-derived factors to brain communication in brain diseases
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Emergence of Caenorhabditis elegans as a Model Organism for Dissecting the Gut–Brain Axis
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Nie, S., & Ge, Y. (2023) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-023-12789-6 · Cited by 23 · see citing works
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 23 · see citing works
The Impact of Human Microbiotas in Hematopoietic Stem Cell and Organ Transplantation
Sen, T., & Thummer, R. P. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.932228 · Cited by 22 · see citing works
Age-dependent effects of gut microbiota metabolites on brain resident macrophages
Hasavci, D., & Blank, T. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2022.944526 · Cited by 23 · see citing works
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The Effects of Immune System Modulation on Prion Disease Susceptibility and Pathogenesis
Mabbott, N. A., Bradford, B. M., Pal, R., Young, R. A., & Donaldson, D. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21197299 · Cited by 20 · see citing works
Association Between Bowel Movement Pattern and Cognitive Function
Ma, C., Li, Y., Mei, Z., Yuan, C., Kang, J. H., Grodstein, F., Ascherio, A., Willett, W. C., Chan, A. T., Huttenhower, C., et al. (2023) · Neurology · doi:10.1212/wnl.0000000000207849 · Cited by 23 · see citing works
Neuroimmune multi-hit perspective of coronaviral infection
Hayley, S. P., & Sun, H. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02282-0 · Cited by 21 · see citing works
Toward understanding links between the microbiome and neurotransmitters
Lynch, J. B., & Hsiao, E. Y. (2023) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14993 · Cited by 20 · see citing works
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The Impact of Alcohol-Induced Dysbiosis on Diseases and Disorders of the Central Nervous System
Liu, X., Vigorito, M., Huang, W., Khan, M. A. S., & Chang, S. L. (2021) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-021-10033-4 · Cited by 19 · see citing works
Effects of Catalpol on Alzheimer’s Disease and Its Mechanisms
Chen, H., Deng, C., Meng, Z., & Meng, S. (2022) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2022/2794243 · Cited by 19 · see citing works
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Applications of Raman spectroscopy in the diagnosis and monitoring of neurodegenerative diseases
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The microbiome-gut-brain axis in nutritional neuroscience
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Unraveling the Gut‐Brain‐Immune Interplay in Herpes Simplex Virus‐Associated Neurodegeneration
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Microbiome Alterations and Alzheimer’s Disease: Modeling Strategies with Transgenic Mice
López-Villodres, J. A., Escamilla, A., Mercado-Sáenz, S., Alba-Tercedor, C., Rodríguez‐Pérez, L., Arranz‐Salas, I., Sanchez-Varo, R. M., & Bermúdez, D. (2023) · Biomedicines · doi:10.3390/biomedicines11071846 · Cited by 16 · see citing works
- Authors
- Fang, P., Kazmi, S. A., Jameson, K. G., & Hsiao, E. Y.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Fang, P.
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 28
- Issue
- 2
- Pages
- 201-222
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC7430034
- OpenAlex
- W3048918321
- Cited by
- 226
- References
- 165
- Citations by year
- 2026: 19 · 2025: 33 · 2024: 61 · 2023: 45 · 2022: 41 · 2021: 22 · 2020: 3 · 2017: 1
- FWCI
- 2.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- New York Stem Cell Foundation
- Chan Zuckerberg Initiative
- David and Lucile Packard Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- gut microbiota, neurodegenerative diseases, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, aging, microbiota-targeted interventions, host-microbe interactions, neuroinflammation, metabolic mechanisms, disease susceptibility
- MeSH terms
- Gastrointestinal Microbiome, Aging, Alzheimer Disease, Amyotrophic Lateral Sclerosis, Animals, Central Nervous System, Disease Models, Animal, Humans, Huntington Disease, Parkinson Disease, Peripheral Nervous System, Neurodegenerative Diseases, Mice, Cognitive Dysfunction
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