Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease

By T. Sampson, Justine W. Debelius, Taren M. Thron, Stefan Janssen, Gauri G. Shastri, Z. Ilhan, Collin Challis, Catherine E. Schretter, S. Rocha, Viviana Gradinaru and 7 more. Cell, 2016

3,201 citations recorded by the source corpus.

Summary The intestinal microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders. However, a functional link between gut bacteria and neurodegenerative diseases remains unexplored. Synucleinopathies are characterized by aggregation of the protein α-synuclein (αSyn), often resulting in motor dysfunction as exemplified by Parkinson's disease (PD). Using mice that overexpress αSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and αSyn pathology. Antibiotic treatment ameliorates, while microbial re-colonization promotes, pathophysiology in adult animals, suggesting postnatal signaling between the gut and the brain modulates disease. Indeed, oral administration of specific microbial metabolites to germ-free mice promotes neuroinflammation and motor symptoms. Remarkably, colonization of αSyn-overexpressing mice with microbiota from PD patients enhances physical impairments compared to microbiota transplants from healthy human donors. These findings reveal that gut bacteria regulate movement disorders in mice, and suggest that alterations in the human microbiome represent a risk factor for PD.

Subfields: Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/a9dd93b39a2b4dd4bd0ec73c88582547610eeee7

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In Molecular Biology

1. J. Cryan
2. Ted G. Dinan
3. G. Clarke
4. S. Mazmanian
5. C. Stanton
6. Rob Knight
7. Peter J. Turnbaugh
8. Ygor P. Silva

In Neurology

1. B. Cree
2. Stephen L. Hauser
3. John Q. Trojanowski
4. H. Ko
5. Andrew J. Saykin

Citations in the corpus

• The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates (2018, background): “In a mouse model of PD, it has been demonstrated that GM is key player in motor deficits and microglia activation (172).”
• Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024, background): “241 Alterations in the gut microbiota and in fl ammatory agents have an impact on the KYN pathway, metabolism, and toxin metabolism in the periphery.”
• Transneuronal Propagation of Pathologic α-Synuclein from the Gut to the Brain Models Parkinson's Disease. (2019, background): “Recent studies on the gut microbiome suggested that short-chain fatty acids and extracellular fibers, such as curli, produced from microbes in the gastrointestinal tract could affect a-syn aggregation and motor dysfunction (Chapman et al., 2002; Sampson et al., 2016).”
• The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020, background): “In contrast, FMT from PD patient donors worsens disease progression suggesting the presence of specific diseasepromoting microbes (169).”
• Gut Microbiome: Profound Implications for Diet and Disease (2019, background): “Besides dietary intervention, these and other observations suggest that supplementation with prebiotics or probiotics could be used to improve cognitive symptoms associated with neurological conditions ranging from autism to Alzheimer’s and Parkinson’s [69, 70], giving rise to the notion of “psychob”
• Microbiota in health and diseases (2022, background): “Increased level of certain Prevotella species is associated with mucin synthesis in the gut mucosal layer and production of SCFAs, which are shown to mediate neuroinflammation in mouse models of PD.(67) However, another study has reported a decreased abundance of Prevotella in PD patients compared w”
• Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism (2019, background): “A growing body of evidence links the trillions of microbes that inhabit the human gastrointestinal tract (the human gut microbiota) to neurological conditions, including the debilitating neurodegenerative disorder Parkinson’s disease (1, 2).”
• Altered Bile Acid Profile Associates with Cognitive Impairment in Alzheimer’s Disease – An Emerging Role for Gut Microbiome (2018, background): “Recently, a role for the gut microbiome in motor dysfunction in Parkinson’s disease has been highlighted [13], and several animal models of AD showed a possible role of gut bacteria in amyloid-b pathology [14,15].”
• Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines (2018, background): “There is, therefore, considerable interest in the role of the intestinal microbiota and health and the so-called immune-relevant microbiome (324, 354), with important correlations between inflammation and neurodegenerative disease (430), bacterial β-hydroxybutyrate metabolites (431), and the role of”
• Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice (2019, neutral): “, 2016), and may modify disease symptoms in individuals when coupled with a genetic risk (Luca et al., 2017; Sampson et al., 2016).”