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Gut Bacteria Regulate the Pathogenesis of Huntington’s Disease in Drosophila Model

Chongtham, Anjalika and Yoo, Jung Hyun and Chin, Theodore M. and Akingbesote, Ngozi D. and Huda, Ainul and Marsh, J. Lawrence and Khoshnan, Ali (2022) Gut Bacteria Regulate the Pathogenesis of Huntington’s Disease in Drosophila Model. Frontiers in Neuroscience, 16 . Art. No. 902205. ISSN 1662-4548. PMCID PMC9215115. doi:10.3389/fnins.2022.902205. 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 progression of Huntington’s disease (HD) in transgenic Drosophila melanogaster (fruit fly) models expressing full-length or N-terminal fragments of human mutant huntingtin (HTT) protein. 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 with links to neurodegeneration and other morbidities, accelerates HTT aggregation, aggravates immobility, and shortens lifespan. Similar to antibiotics, treatment of HD flies with small 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 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 models support the involvement of gut-brain networks in the pathogenesis of HD.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.3389/fnins.2022.902205DOIArticle
https://www.frontiersin.org/articles/10.3389/fnins.2022.902205/full#supplementary-materialPublisherSupplementary Material
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9215115PubMed CentralArticle
https://doi.org/10.1101/2021.08.12.456124DOIDiscussion Paper
ORCID:
AuthorORCID
Chongtham, Anjalika0000-0001-8437-3899
Yoo, Jung Hyun0000-0002-5159-8167
Akingbesote, Ngozi D.0000-0001-6390-5729
Huda, Ainul0000-0003-2073-6659
Khoshnan, Ali0000-0002-0070-9808
Alternate Title:Gut bacteria and HD, Gut bacteria modulate Huntington’s disease
Additional Information:© 2022 Chongtham, Yoo, Chin, Akingbesote, Huda, Marsh and Khoshnan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Received: 22 March 2022; Accepted: 12 May 2022; Published: 02 June 2022. We are grateful to Segelski at Stanford for providing the E. coli strains used in these studies, and Yelim Lee for technical assistance. Data Availability Statement: The original contributions presented in this study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author/s. Author Contributions: AK conceived the idea, wrote the manuscript, and acquired the funding. AC contributed to writing and editing the manuscript. AC, JY, TC, NA, and AH performed the experiments. AK, AC, and JY analyzed the data. JM provided the fly stocks. All authors have read and approved the manuscript. Funding was provided through awards to AK by the Huntington’s Disease Society of America (HDSA) and Hereditary Disease Foundation (HDF). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Funders:
Funding AgencyGrant Number
Huntington’s Disease Society of AmericaUNSPECIFIED
Hereditary Disease FoundationUNSPECIFIED
Subject Keywords:Huntington’s disease, microbiota, gut-brain, neurodegeneration, crocin
PubMed Central ID:PMC9215115
DOI:10.3389/fnins.2022.902205
Record Number:CaltechAUTHORS:20210817-140257777
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210817-140257777
Official Citation:Chongtham A, Yoo JH, Chin TM, Akingbesote ND, Huda A, Marsh JL and Khoshnan A (2022) Gut Bacteria Regulate the Pathogenesis of Huntington’s Disease in Drosophila Model. Front. Neurosci. 16:902205. doi: 10.3389/fnins.2022.902205
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:14 Jul 2022 20:14

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