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A gut microbial factor modulates locomotor behavior in Drosophila

Schretter, Catherine E. and Vielmetter, Jost and Bartos, Imre and Márka, Zsuzsa and Márka, Szabolcs and Argade, Sulabha and Mazmanian, Sarkis K. (2018) A gut microbial factor modulates locomotor behavior in Drosophila. Nature, 563 (7731). pp. 402-406. ISSN 0028-0836. http://resolver.caltech.edu/CaltechAUTHORS:20180905-135438422

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[img] Image (JPEG) (Extended Data Fig. 1: Effects of colonization level, bacterial strain, and host diet on L. brevis modulation of locomotion) - Supplemental Material
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[img] Image (JPEG) (Extended Data Fig. 2: Post-eclosion microbial signals decrease host locomotion) - Supplemental Material
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[img] Image (JPEG) (Extended Data Fig. 3: Bacterial-derived products from L. brevis alter locomotion) - Supplemental Material
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[img] Image (JPEG) (Extended Data Fig. 4: Locomotor phenotypes are independent of food intake, anti-microbial peptides, and the immune deficiency (IMD) and Toll pathways) - Supplemental Material
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[img] Image (JPEG) (Extended Data Fig. 5: Modulation of locomotion by the bacterial enzyme, xylose isomerase) - Supplemental Material
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[img] Image (JPEG) (Extended Data Fig. 6: Sleep analysis for mono-colonized flies and flies treated with bacterial factors) - Supplemental Material
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[img] Image (JPEG) (Extended Data Fig. 7: Xylose isomerase activity and key carbohydrates are involved in Xi-mediated changes in locomotion) - Supplemental Material
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[img] Image (JPEG) (Extended Data Fig. 10: Octopamine mediates L. brevis- and Xi-induced changes in locomotion) - Supplemental Material
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Abstract

While research into the biology of animal behaviour has primarily focused on the central nervous system, cues from peripheral tissues and the environment have been implicated in brain development and function. There is emerging evidence that bidirectional communication between the gut and the brain affects behaviours including anxiety, cognition, nociception and social interaction. Coordinated locomotor behaviour is critical for the survival and propagation of animals, and is regulated by internal and external sensory inputs. However, little is known about how the gut microbiome influences host locomotion, or the molecular and cellular mechanisms involved. Here we report that germ-free status or antibiotic treatment results in hyperactive locomotor behaviour in the fruit fly Drosophila melanogaster. Increased walking speed and daily activity in the absence of a gut microbiome are rescued by mono-colonization with specific bacteria, including the fly commensal Lactobacillus brevis. The bacterial enzyme xylose isomerase from L. brevis recapitulates the locomotor effects of microbial colonization by modulating sugar metabolism in flies. Notably, thermogenetic activation of octopaminergic neurons or exogenous administration of octopamine, the invertebrate counterpart of noradrenaline, abrogates the effects of xylose isomerase on Drosophila locomotion. These findings reveal a previously unappreciated role for the gut microbiome in modulating locomotion, and identify octopaminergic neurons as mediators of peripheral microbial cues that regulate motor behaviour in animals.


Item Type:Article
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https://doi.org/10.1038/s41586-018-0634-9DOIArticle
https://rdcu.be/9ZqJPublisherFree ReadCube access
ORCID:
AuthorORCID
Mazmanian, Sarkis K.0000-0003-2713-1513
Additional Information:© 2018 Springer Nature Limited. Received 03 July 2017; Accepted 11 September 2018; Published 24 October 2018. We thank H. Chu, G. Sharon, W.-L. Wu, J. K. Scarpa, E. D. Hoopfer and the Mazmanian laboratory for critiques; A. A. Aravin and K. Fejes Tόth for use of their laboratory space; D. J. Anderson, H. A. Lester, V. Gradinaru and M.-F. Chesselet for discussions; A. R. Sandoval, M. Meyerowitz and M. Smalley for technical support; Y. Garcia-Flores for administrative support; D. C. Hall for creating custom Python scripts; W.-J. Lee for the L. brevis^(EW), L. plantarum^(WJL) and Acetobacter pomorumbacterial strains; the Yale Coli Genetic Stock Center for wild-type and mutant E. coli strains; M. H. Dickinson, D. J. Anderson, A. A. Aravin, and K. Fejes Tόth for fly lines; the GlycoAnalytics Core for help with carbohydrate analysis; and M. Fischbach and M. Funabashi for the pGID023 vector and advice. Imaging was performed in the Biological Imaging Facility, with the support of the Caltech Beckman Institute and the Arnold and Mabel Beckman Foundation. C.E.S. was partially supported by the Center for Environmental Microbial Interactions at Caltech. This project was funded by grants from the NIH (NS085910) and the Heritage Medical Research Institute to S.K.M. Code availability: Custom code for bout analysis is available from the corresponding authors upon request. Reporting summary: Further information on experimental design is available in the Nature Research Reporting Summary linked to this paper. Data availability: All datasets generated are available from the corresponding authors upon request. Reviewer information: Nature thanks P. Bercik, C.-F. Wu and the other anonymous reviewer(s) for their contribution to the peer review of this work. Author Contributions: C.E.S. designed, performed and analysed most of the experiments. J.V. assisted with experimental design for biochemical analysis. I.B., Z.M., and S.M. assisted with gait analysis experiments. S.A. performed carbohydrate quantification. C.E.S. and S.K.M supervised the project. C.E.S. and S.K.M. wrote the manuscript with assistance from all authors. The authors declare no competing interests.
Group:Heritage Medical Research Institute, Caltech Center for Environmental Microbial Interactions (CEMI)
Funders:
Funding AgencyGrant Number
Caltech Beckman InstituteUNSPECIFIED
Arnold and Mabel Beckman FoundationUNSPECIFIED
Caltech Center for Environmental Microbial Interactions (CEMI)UNSPECIFIED
NIHNS085910
Heritage Medical Research InstituteUNSPECIFIED
Record Number:CaltechAUTHORS:20180905-135438422
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20180905-135438422
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:89397
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:24 Oct 2018 17:50
Last Modified:20 Nov 2018 18:36

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