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Mutant and curli-producing E. coli enhance the disease phenotype in a hSOD1-G93A mouse model of ALS
The gut microbiome is a potential non-genetic contributing factor for Amyotrophic Lateral Sclerosis. Differences in gut microbial communities have been detected between ALS subjects and healthy controls, including an increase in Escherichia coli in ALS subjects. E. coli and other gram-negative bacte...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10097672/ https://www.ncbi.nlm.nih.gov/pubmed/37045868 http://dx.doi.org/10.1038/s41598-023-32594-5 |
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author | Kurlawala, Zimple McMillan, Joseph D. Singhal, Richa A. Morehouse, Johnny Burke, Darlene A. Sears, Sophia M. Duregon, Eleonora Beverly, Levi J. Siskind, Leah J. Friedland, Robert P. |
author_facet | Kurlawala, Zimple McMillan, Joseph D. Singhal, Richa A. Morehouse, Johnny Burke, Darlene A. Sears, Sophia M. Duregon, Eleonora Beverly, Levi J. Siskind, Leah J. Friedland, Robert P. |
author_sort | Kurlawala, Zimple |
collection | PubMed |
description | The gut microbiome is a potential non-genetic contributing factor for Amyotrophic Lateral Sclerosis. Differences in gut microbial communities have been detected between ALS subjects and healthy controls, including an increase in Escherichia coli in ALS subjects. E. coli and other gram-negative bacteria produce curli proteins, which are functional bacterial amyloids. We examined whether long-term curli overexposure in the gut can exacerbate the development and progression of ALS. We utilized the slow-developing hSOD1-G93A mouse model of ALS with their C57BL/6J WT littermate controls, including males and females, with a total of 91 animals. These mice were on a normal chow diet and fed curli-producing or curli-nonproducing (mutant) E. coli in applesauce (vehicle) 3 times/week, from 1 through 7 months of age. Male hSOD1 mice demonstrated gradual slowing in running speed month 4 onwards, while females exhibited no signs of locomotive impairment even at 7 months of age. Around the same time, male hSOD1 mice showed a gradual increase in frequency of peripheral CD19(+) B cells. Among the male hSOD1 group, chronic gut exposure to curli-producing E. coli led to significant shifts in α- and β-diversities. Curli-exposed males showed suppression of immune responses in circulation, but an increase in markers of inflammation, autophagy and protein turnover in skeletal muscle. Some of these markers were also changed in mutant E. coli-exposed mice, including astrogliosis in the brainstem and demyelination in the lumbar spinal cord. Overall, chronic overexposure to a commensal bacteria like E. coli led to distant organ pathology in our model, without the presence of a leaky gut at 6 months. Mechanisms underlying gut-distant organ communication are of tremendous interest to all disciplines. |
format | Online Article Text |
id | pubmed-10097672 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-100976722023-04-14 Mutant and curli-producing E. coli enhance the disease phenotype in a hSOD1-G93A mouse model of ALS Kurlawala, Zimple McMillan, Joseph D. Singhal, Richa A. Morehouse, Johnny Burke, Darlene A. Sears, Sophia M. Duregon, Eleonora Beverly, Levi J. Siskind, Leah J. Friedland, Robert P. Sci Rep Article The gut microbiome is a potential non-genetic contributing factor for Amyotrophic Lateral Sclerosis. Differences in gut microbial communities have been detected between ALS subjects and healthy controls, including an increase in Escherichia coli in ALS subjects. E. coli and other gram-negative bacteria produce curli proteins, which are functional bacterial amyloids. We examined whether long-term curli overexposure in the gut can exacerbate the development and progression of ALS. We utilized the slow-developing hSOD1-G93A mouse model of ALS with their C57BL/6J WT littermate controls, including males and females, with a total of 91 animals. These mice were on a normal chow diet and fed curli-producing or curli-nonproducing (mutant) E. coli in applesauce (vehicle) 3 times/week, from 1 through 7 months of age. Male hSOD1 mice demonstrated gradual slowing in running speed month 4 onwards, while females exhibited no signs of locomotive impairment even at 7 months of age. Around the same time, male hSOD1 mice showed a gradual increase in frequency of peripheral CD19(+) B cells. Among the male hSOD1 group, chronic gut exposure to curli-producing E. coli led to significant shifts in α- and β-diversities. Curli-exposed males showed suppression of immune responses in circulation, but an increase in markers of inflammation, autophagy and protein turnover in skeletal muscle. Some of these markers were also changed in mutant E. coli-exposed mice, including astrogliosis in the brainstem and demyelination in the lumbar spinal cord. Overall, chronic overexposure to a commensal bacteria like E. coli led to distant organ pathology in our model, without the presence of a leaky gut at 6 months. Mechanisms underlying gut-distant organ communication are of tremendous interest to all disciplines. Nature Publishing Group UK 2023-04-12 /pmc/articles/PMC10097672/ /pubmed/37045868 http://dx.doi.org/10.1038/s41598-023-32594-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Kurlawala, Zimple McMillan, Joseph D. Singhal, Richa A. Morehouse, Johnny Burke, Darlene A. Sears, Sophia M. Duregon, Eleonora Beverly, Levi J. Siskind, Leah J. Friedland, Robert P. Mutant and curli-producing E. coli enhance the disease phenotype in a hSOD1-G93A mouse model of ALS |
title | Mutant and curli-producing E. coli enhance the disease phenotype in a hSOD1-G93A mouse model of ALS |
title_full | Mutant and curli-producing E. coli enhance the disease phenotype in a hSOD1-G93A mouse model of ALS |
title_fullStr | Mutant and curli-producing E. coli enhance the disease phenotype in a hSOD1-G93A mouse model of ALS |
title_full_unstemmed | Mutant and curli-producing E. coli enhance the disease phenotype in a hSOD1-G93A mouse model of ALS |
title_short | Mutant and curli-producing E. coli enhance the disease phenotype in a hSOD1-G93A mouse model of ALS |
title_sort | mutant and curli-producing e. coli enhance the disease phenotype in a hsod1-g93a mouse model of als |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10097672/ https://www.ncbi.nlm.nih.gov/pubmed/37045868 http://dx.doi.org/10.1038/s41598-023-32594-5 |
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