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Gut bacteria regulate the pathogenesis of Huntington’s disease in Drosophila

Chongtham, Anjalika and Yoo, Jung Hyun and Chin, Theodore M. and Akingbesote, Ngozi D. and Huda, Ainul and Khoshnan, Ali (2021) Gut bacteria regulate the pathogenesis of Huntington’s disease in Drosophila. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20210817-140257777

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Abstract

Changes in the composition of gut microbiota are implicated in the pathogenesis of several neurodegenerative disorders. Here, we investigated whether gut bacteria affect the hallmarks of Huntington’s disease (HD) in transgenic Drosophila melanogaster (fruit fly) models expressing human full-length or N-terminal fragments of mutant huntingtin (HTT) protein, here referred to as HD flies. We find that elimination of commensal gut bacteria by antibiotics reduces the aggregation of amyloidogenic N-terminal fragments of HTT and delays the development of motor defects. Conversely, colonization of HD flies with Escherichia coli (E. coli), a known pathobiont of human gut, accelerates HTT aggregation, aggravates immobility and shortens life span. Similar to antibiotics, treatment of HD flies with compounds such as luteolin, a flavone, or crocin a beta-carotenoid, ameliorates disease phenotypes and promotes survival. Crocin prevents colonization of E. coli in the HD flies gut and alters the levels of commensal bacteria, which may be linked to its protective effects. The opposing effects of E. coli and crocin on HTT aggregation, motor defects and survival in transgenic Drosophila support the involvement of gut-brain networks in the pathogenesis of HD.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2021.08.12.456124DOIDiscussion Paper
ORCID:
AuthorORCID
Chongtham, Anjalika0000-0001-8437-3899
Yoo, Jung Hyun0000-0002-5159-8167
Huda, Ainul0000-0003-2073-6659
Khoshnan, Ali0000-0002-0070-9808
Alternate Title:Gut bacteria and HD
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This version posted August 13, 2021. We are grateful to Dr. Segelski at Stanford for providing the E. coli strains used in these studies, Dr. J. Lawrence Marsh for providing the HD fly lines and Yelim Lee for technical assistance. Funding was provided by awards to AK by Huntington’s Disease Society of America (HDSA) and Hereditary Disease Foundation (HDF). Authors’ contributions: AK conceived the idea wrote the manuscript and acquired the funding. AC, JHY, TC, NDA, and AH performed the experiments. AK, AC, and JHY analyzed the data. All authors have read and approved the paper. Authors declare no competing interest.
Funders:
Funding AgencyGrant Number
Huntington’s Disease Society of AmericaUNSPECIFIED
Hereditary Disease FoundationUNSPECIFIED
Subject Keywords:Huntington’s disease, Microbiota, Gut-brain, E. coli, Crocin
DOI:10.1101/2021.08.12.456124
Record Number:CaltechAUTHORS:20210817-140257777
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210817-140257777
Official Citation:Gut bacteria regulate the pathogenesis of Huntington’s disease in Drosophila. Anjalika Chongtham, Jung Hyun Yoo, Theodore M. Chin, Ngozi D. Akingbesote, Ainul Huda, Ali Khoshnan. bioRxiv 2021.08.12.456124; doi: https://doi.org/10.1101/2021.08.12.456124
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:110281
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:17 Aug 2021 15:28
Last Modified:16 Nov 2021 19:40

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