Probiotic Bacillus subtilis Protects against α-Synuclein Aggregation in C. elegans

María Eugenia Goya; Feng Xue; Cristina Sampedro-Torres-Quevedo; Sofia Arnaouteli; Lourdes Riquelme-Dominguez; Andrés Romanowski; Jack Brydon; Kathryn L. Ball; Nicola R. Stanley-Wall; Maria Doitsidou

doi:10.1016/j.celrep.2019.12.078

Probiotic Bacillus subtilis Protects against α-Synuclein Aggregation in C. elegans

María Eugenia Goya, Feng Xue, Cristina Sampedro-Torres-Quevedo, Sofia Arnaouteli, Lourdes Riquelme-Dominguez, Andrés Romanowski, Jack Brydon, Kathryn L. Ball, Nicola R. Stanley-Wall, Maria Doitsidou^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

How the gut microbiome affects Parkinson's disease remains unclear. Goya et al. show that the probiotic B. subtilis strain PXN21 inhibits and clears α-synuclein aggregation in a C. elegans model. The bacterium acts via metabolites and biofilm formation to activate protective pathways in the host, including DAF-16/FOXO and sphingolipid metabolism.

Original language	English
Pages (from-to)	367-380.e7
Journal	Cell Reports
Volume	30
Issue number	2
DOIs	https://doi.org/10.1016/j.celrep.2019.12.078
Publication status	Published - 14 Jan 2020
Externally published	Yes

Bibliographical note

Funding Information:
We thank Claire B?nard, Sebastian Greiss, Oliver Hobert, Anton Gartner, Luisa Cochella, Emanuel Busch, Diego Golombek, Ailish Tynan and Claudio Valverde for helpful discussions and feedback on the manuscript; EdinOmics and Tessa Moses for expert assistance; Viktoria Bajuszova for technical support; Francis Turner and Edinburgh Genomics for RNA-seq analysis; Jos? C. Riquelme, Crispin Jordan, and Ignacio Spiousas for input on statistical analysis; Ellen Nollen for the NL5901 strain; Life Science Editors for editing assistance; and Ms. Vickie Cunnane for her generous donation. Funding sources include EMBO ALTF 529-2017 and MSCA-IF 798650 to M.E.G.; Parkinson's UK, United Kingdom, project grant PRO-17-21 to M.D. and F.X.; BBSRC, United Kingdom, BB/P001335/1 grant to N.R.S.-W. and BB/R50614X/1 grant to K.L.B. which supports J.B.; and the Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund ISSF3 award to M.D. Some strains were provided by the CGC, funded by NIH Office of Research Infrastructure Programs (P40 OD010440), the Bacillus Genetic Stock Centre funded by the National Science Foundation (1756219), and the Gene Knockout Project at the Oklahoma Medical Research Foundation. The Wormlab was acquired with funding from the Muir Maxwell Epilepsy Centre. M.D. M.E.G. F.X. C.S.-T.-Q. and L.R.-D. designed, performed, and analyzed experiments with C. elegans; J.B. and K.L.B. designed, performed, and analyzed western blot experiments; N.R.S.-W. and S.A. designed, performed, and analyzed B. subtilis biofilm experiments and generated bacterial strains; A.R. contributed with the RNA-seq and qRT-PCR analysis; and M.D. provided oversight for the project and wrote the paper. All authors contributed to editing the manuscript. The authors declare no competing interests.

Funding Information:
We thank Claire Bénard, Sebastian Greiss, Oliver Hobert, Anton Gartner, Luisa Cochella, Emanuel Busch, Diego Golombek, Ailish Tynan and Claudio Valverde for helpful discussions and feedback on the manuscript; EdinOmics and Tessa Moses for expert assistance; Viktoria Bajuszova for technical support; Francis Turner and Edinburgh Genomics for RNA-seq analysis; José C. Riquelme, Crispin Jordan, and Ignacio Spiousas for input on statistical analysis; Ellen Nollen for the NL5901 strain; Life Science Editors for editing assistance; and Ms. Vickie Cunnane for her generous donation. Funding sources include EMBO ALTF 529-2017 and MSCA-IF 798650 to M.E.G.; Parkinson's UK , United Kingdom, project grant PRO-17-21 to M.D. and F.X.; BBSRC , United Kingdom, BB/P001335/1 grant to N.R.S.-W. and BB/R50614X/1 grant to K.L.B. which supports J.B.; and the Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund ISSF3 award to M.D. Some strains were provided by the CGC , funded by NIH Office of Research Infrastructure Programs ( P40 OD010440 ), the Bacillus Genetic Stock Centre funded by the National Science Foundation ( 1756219 ), and the Gene Knockout Project at the Oklahoma Medical Research Foundation . The Wormlab was acquired with funding from the Muir Maxwell Epilepsy Centre.

Publisher Copyright:
© 2019 The Author(s)

Funding

We thank Claire B?nard, Sebastian Greiss, Oliver Hobert, Anton Gartner, Luisa Cochella, Emanuel Busch, Diego Golombek, Ailish Tynan and Claudio Valverde for helpful discussions and feedback on the manuscript; EdinOmics and Tessa Moses for expert assistance; Viktoria Bajuszova for technical support; Francis Turner and Edinburgh Genomics for RNA-seq analysis; Jos? C. Riquelme, Crispin Jordan, and Ignacio Spiousas for input on statistical analysis; Ellen Nollen for the NL5901 strain; Life Science Editors for editing assistance; and Ms. Vickie Cunnane for her generous donation. Funding sources include EMBO ALTF 529-2017 and MSCA-IF 798650 to M.E.G.; Parkinson's UK, United Kingdom, project grant PRO-17-21 to M.D. and F.X.; BBSRC, United Kingdom, BB/P001335/1 grant to N.R.S.-W. and BB/R50614X/1 grant to K.L.B. which supports J.B.; and the Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund ISSF3 award to M.D. Some strains were provided by the CGC, funded by NIH Office of Research Infrastructure Programs (P40 OD010440), the Bacillus Genetic Stock Centre funded by the National Science Foundation (1756219), and the Gene Knockout Project at the Oklahoma Medical Research Foundation. The Wormlab was acquired with funding from the Muir Maxwell Epilepsy Centre. M.D. M.E.G. F.X. C.S.-T.-Q. and L.R.-D. designed, performed, and analyzed experiments with C. elegans; J.B. and K.L.B. designed, performed, and analyzed western blot experiments; N.R.S.-W. and S.A. designed, performed, and analyzed B. subtilis biofilm experiments and generated bacterial strains; A.R. contributed with the RNA-seq and qRT-PCR analysis; and M.D. provided oversight for the project and wrote the paper. All authors contributed to editing the manuscript. The authors declare no competing interests. We thank Claire Bénard, Sebastian Greiss, Oliver Hobert, Anton Gartner, Luisa Cochella, Emanuel Busch, Diego Golombek, Ailish Tynan and Claudio Valverde for helpful discussions and feedback on the manuscript; EdinOmics and Tessa Moses for expert assistance; Viktoria Bajuszova for technical support; Francis Turner and Edinburgh Genomics for RNA-seq analysis; José C. Riquelme, Crispin Jordan, and Ignacio Spiousas for input on statistical analysis; Ellen Nollen for the NL5901 strain; Life Science Editors for editing assistance; and Ms. Vickie Cunnane for her generous donation. Funding sources include EMBO ALTF 529-2017 and MSCA-IF 798650 to M.E.G.; Parkinson's UK , United Kingdom, project grant PRO-17-21 to M.D. and F.X.; BBSRC , United Kingdom, BB/P001335/1 grant to N.R.S.-W. and BB/R50614X/1 grant to K.L.B. which supports J.B.; and the Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund ISSF3 award to M.D. Some strains were provided by the CGC , funded by NIH Office of Research Infrastructure Programs ( P40 OD010440 ), the Bacillus Genetic Stock Centre funded by the National Science Foundation ( 1756219 ), and the Gene Knockout Project at the Oklahoma Medical Research Foundation . The Wormlab was acquired with funding from the Muir Maxwell Epilepsy Centre.

Keywords

B. subtilis
biofilm
C. elegans
DAF-16/FOXO
dietary restriction
microbiota
Parkinson's disease
probiotics
sphingolipid metabolism
α-synuclein

Access to Document

10.1016/j.celrep.2019.12.078

PIIS2211124719317437Final published version, 4.44 MBLicence: CC BY

Cite this

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title = "Probiotic Bacillus subtilis Protects against α-Synuclein Aggregation in C. elegans",

abstract = "How the gut microbiome affects Parkinson's disease remains unclear. Goya et al. show that the probiotic B. subtilis strain PXN21 inhibits and clears α-synuclein aggregation in a C. elegans model. The bacterium acts via metabolites and biofilm formation to activate protective pathways in the host, including DAF-16/FOXO and sphingolipid metabolism.",

keywords = "B. subtilis, biofilm, C. elegans, DAF-16/FOXO, dietary restriction, microbiota, Parkinson's disease, probiotics, sphingolipid metabolism, α-synuclein",

author = "Goya, {Mar{\'i}a Eugenia} and Feng Xue and Cristina Sampedro-Torres-Quevedo and Sofia Arnaouteli and Lourdes Riquelme-Dominguez and Andr{\'e}s Romanowski and Jack Brydon and Ball, {Kathryn L.} and Stanley-Wall, {Nicola R.} and Maria Doitsidou",

note = "Funding Information: We thank Claire B?nard, Sebastian Greiss, Oliver Hobert, Anton Gartner, Luisa Cochella, Emanuel Busch, Diego Golombek, Ailish Tynan and Claudio Valverde for helpful discussions and feedback on the manuscript; EdinOmics and Tessa Moses for expert assistance; Viktoria Bajuszova for technical support; Francis Turner and Edinburgh Genomics for RNA-seq analysis; Jos? C. Riquelme, Crispin Jordan, and Ignacio Spiousas for input on statistical analysis; Ellen Nollen for the NL5901 strain; Life Science Editors for editing assistance; and Ms. Vickie Cunnane for her generous donation. Funding sources include EMBO ALTF 529-2017 and MSCA-IF 798650 to M.E.G.; Parkinson's UK, United Kingdom, project grant PRO-17-21 to M.D. and F.X.; BBSRC, United Kingdom, BB/P001335/1 grant to N.R.S.-W. and BB/R50614X/1 grant to K.L.B. which supports J.B.; and the Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund ISSF3 award to M.D. Some strains were provided by the CGC, funded by NIH Office of Research Infrastructure Programs (P40 OD010440), the Bacillus Genetic Stock Centre funded by the National Science Foundation (1756219), and the Gene Knockout Project at the Oklahoma Medical Research Foundation. The Wormlab was acquired with funding from the Muir Maxwell Epilepsy Centre. M.D. M.E.G. F.X. C.S.-T.-Q. and L.R.-D. designed, performed, and analyzed experiments with C. elegans; J.B. and K.L.B. designed, performed, and analyzed western blot experiments; N.R.S.-W. and S.A. designed, performed, and analyzed B. subtilis biofilm experiments and generated bacterial strains; A.R. contributed with the RNA-seq and qRT-PCR analysis; and M.D. provided oversight for the project and wrote the paper. All authors contributed to editing the manuscript. The authors declare no competing interests. Funding Information: We thank Claire B{\'e}nard, Sebastian Greiss, Oliver Hobert, Anton Gartner, Luisa Cochella, Emanuel Busch, Diego Golombek, Ailish Tynan and Claudio Valverde for helpful discussions and feedback on the manuscript; EdinOmics and Tessa Moses for expert assistance; Viktoria Bajuszova for technical support; Francis Turner and Edinburgh Genomics for RNA-seq analysis; Jos{\'e} C. Riquelme, Crispin Jordan, and Ignacio Spiousas for input on statistical analysis; Ellen Nollen for the NL5901 strain; Life Science Editors for editing assistance; and Ms. Vickie Cunnane for her generous donation. Funding sources include EMBO ALTF 529-2017 and MSCA-IF 798650 to M.E.G.; Parkinson's UK , United Kingdom, project grant PRO-17-21 to M.D. and F.X.; BBSRC , United Kingdom, BB/P001335/1 grant to N.R.S.-W. and BB/R50614X/1 grant to K.L.B. which supports J.B.; and the Wellcome Trust-University of Edinburgh Institutional Strategic Support Fund ISSF3 award to M.D. Some strains were provided by the CGC , funded by NIH Office of Research Infrastructure Programs ( P40 OD010440 ), the Bacillus Genetic Stock Centre funded by the National Science Foundation ( 1756219 ), and the Gene Knockout Project at the Oklahoma Medical Research Foundation . The Wormlab was acquired with funding from the Muir Maxwell Epilepsy Centre. Publisher Copyright: {\textcopyright} 2019 The Author(s)",

year = "2020",

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doi = "10.1016/j.celrep.2019.12.078",

language = "English",

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T1 - Probiotic Bacillus subtilis Protects against α-Synuclein Aggregation in C. elegans

AU - Goya, María Eugenia

AU - Xue, Feng

AU - Sampedro-Torres-Quevedo, Cristina

AU - Arnaouteli, Sofia

AU - Riquelme-Dominguez, Lourdes

AU - Romanowski, Andrés

AU - Brydon, Jack

AU - Ball, Kathryn L.

AU - Stanley-Wall, Nicola R.

AU - Doitsidou, Maria

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Y1 - 2020/1/14

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Probiotic Bacillus subtilis Protects against α-Synuclein Aggregation in C. elegans

Abstract

Bibliographical note

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Keywords

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