TY - CHAP
T1 - The gut microbiome in Parkinson's disease
T2 - A culprit or a bystander?
AU - Keshavarzian, Ali
AU - Engen, Phillip
AU - Bonvegna, Salvatore
AU - Cilia, Roberto
N1 - Funding Information:
A.K. and P.E. would like to thank Drs. Christopher B. Forsyth, Robin M. Voigt, Geethika Earthineni and Ms. Vivian Ramirez, and Shohreh Raeisi for their contribution to this book chapter. A.K. would also like to acknowledge philanthropy funding from Mrs. Barbara and Mr. Larry Field, Mrs. Ellen and Mr. Philip Glass, and Mrs. Marcia and Mr. Silas Keehn. R.C. would like to thank Dr. Emanuele Cereda for brainstorming on the relationship between gut microbiota and PD pathophysiology as well as his helpful comments during the manuscript revision. S.B. and R.C. are thankful to the “Fondazione Grigioni per il Morbo di Parkinson” (Milano, Italy) for supporting the clinical studies on gut microbiota in patients with Parkinsonism.
Publisher Copyright:
© 2020 Elsevier B.V.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020
Y1 - 2020
N2 - In recent years, large-scale metagenomics projects such as the Human Microbiome Project placed the gut microbiota under the spotlight of research on its role in health and in the pathogenesis several diseases, as it can be a target for novel therapeutical approaches. The emerging concept of a microbiota modulation of the gut-brain axis in the pathogenesis of neurodegenerative disorders has been explored in several studies in animal models, as well as in human subjects. Particularly, research on changes in the composition of gut microbiota as a potential trigger for alpha-synuclein (α-syn) pathology in Parkinson's disease (PD) has gained increasing interest. In the present review, we first provide the basis to the understanding of the role of gut microbiota in healthy subjects and the molecular basis of the gut-brain interaction, focusing on metabolic and neuroinflammatory factors that could trigger the alpha-synuclein conformational changes and aggregation. Then, we critically explored preclinical and clinical studies reporting on the changes in gut microbiota in PD, as compared to healthy subjects. Furthermore, we examined the relationship between the gut microbiota and PD clinical features, discussing data consistently reported across studies, as well as the potential sources of inconsistencies. As a further step toward understanding the effects of gut microbiota on PD, we discussed the relationship between dysbiosis and response to dopamine replacement therapy, focusing on Levodopa metabolism. We conclude that further studies are needed to determine whether the gut microbiota changes observed so far in PD patients is the cause or, instead, it is merely a consequence of lifestyle changes associated with the disease. Regardless, studies so far strongly suggest that changes in microbiota appears to be impactful in pathogenesis of neuroinflammation. Thus, dysbiotic microbiota in PD could influence the disease course and response to medication, especially Levodopa. Future research will assess the impact of microbiota-directed therapeutic intervention in PD patients.
AB - In recent years, large-scale metagenomics projects such as the Human Microbiome Project placed the gut microbiota under the spotlight of research on its role in health and in the pathogenesis several diseases, as it can be a target for novel therapeutical approaches. The emerging concept of a microbiota modulation of the gut-brain axis in the pathogenesis of neurodegenerative disorders has been explored in several studies in animal models, as well as in human subjects. Particularly, research on changes in the composition of gut microbiota as a potential trigger for alpha-synuclein (α-syn) pathology in Parkinson's disease (PD) has gained increasing interest. In the present review, we first provide the basis to the understanding of the role of gut microbiota in healthy subjects and the molecular basis of the gut-brain interaction, focusing on metabolic and neuroinflammatory factors that could trigger the alpha-synuclein conformational changes and aggregation. Then, we critically explored preclinical and clinical studies reporting on the changes in gut microbiota in PD, as compared to healthy subjects. Furthermore, we examined the relationship between the gut microbiota and PD clinical features, discussing data consistently reported across studies, as well as the potential sources of inconsistencies. As a further step toward understanding the effects of gut microbiota on PD, we discussed the relationship between dysbiosis and response to dopamine replacement therapy, focusing on Levodopa metabolism. We conclude that further studies are needed to determine whether the gut microbiota changes observed so far in PD patients is the cause or, instead, it is merely a consequence of lifestyle changes associated with the disease. Regardless, studies so far strongly suggest that changes in microbiota appears to be impactful in pathogenesis of neuroinflammation. Thus, dysbiotic microbiota in PD could influence the disease course and response to medication, especially Levodopa. Future research will assess the impact of microbiota-directed therapeutic intervention in PD patients.
KW - Gut microbiota
KW - Gut-brain axis
KW - Levodopa
KW - Neuroinflammation
KW - Parkinson's disease
KW - Short-chain-fatty-acids
UR - http://www.scopus.com/inward/record.url?scp=85081248568&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85081248568&partnerID=8YFLogxK
U2 - 10.1016/bs.pbr.2020.01.004
DO - 10.1016/bs.pbr.2020.01.004
M3 - Chapter
C2 - 32247371
AN - SCOPUS:85081248568
SN - 9780444642608
T3 - Progress in Brain Research
SP - 357
EP - 450
BT - Progress in Brain Research
A2 - Björklund, Anders
A2 - Cenci, M. Angela
PB - Elsevier B.V.
ER -