Gut bacterial metabolites modulate endoplasmic reticulum stress
Background The endoplasmic reticulum (ER) is a membranous organelle that maintains proteostasis and cellular homeostasis, controlling the fine balance between health and disease. Dysregulation of the ER stress response has been implicated in intestinal inflammation associated with i...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BioMed Central
2021
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| Online Access: | https://hdl.handle.net/1721.1/133015 |
| _version_ | 1826192244794720256 |
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| author | Ke, Xiaobo You, Kwontae Pichaud, Matthieu Haiser, Henry J. Graham, Daniel B. Vlamakis, Hera Porter, Jeffrey A. Xavier, Ramnik J. |
| author2 | Massachusetts Institute of Technology. Center for Microbiome Informatics and Therapeutics |
| author_facet | Massachusetts Institute of Technology. Center for Microbiome Informatics and Therapeutics Ke, Xiaobo You, Kwontae Pichaud, Matthieu Haiser, Henry J. Graham, Daniel B. Vlamakis, Hera Porter, Jeffrey A. Xavier, Ramnik J. |
| author_sort | Ke, Xiaobo |
| collection | MIT |
| description | Background
The endoplasmic reticulum (ER) is a membranous organelle that maintains proteostasis and cellular homeostasis, controlling the fine balance between health and disease. Dysregulation of the ER stress response has been implicated in intestinal inflammation associated with inflammatory bowel disease (IBD), a chronic condition characterized by changes to the mucosa and alteration of the gut microbiota. While the microbiota and microbially derived metabolites have also been implicated in ER stress, examples of this connection remain limited to a few observations from pathogenic bacteria. Furthermore, the mechanisms underlying the effects of bacterial metabolites on ER stress signaling have not been well established.
Results
Utilizing an XBP1s-GFP knock-in reporter colorectal epithelial cell line, we screened 399 microbiome-related metabolites for ER stress pathway modulation. We find both ER stress response inducers (acylated dipeptide aldehydes and bisindole methane derivatives) and suppressors (soraphen A) and characterize their activities on ER stress gene transcription and translation. We further demonstrate that these molecules modulate the ER stress pathway through protease inhibition or lipid metabolism interference.
Conclusions
Our study identified novel links between classes of gut microbe-derived metabolites and the ER stress response, suggesting the potential for these metabolites to contribute to gut ER homeostasis and providing insight into the molecular mechanisms by which gut microbes impact intestinal epithelial cell homeostasis. |
| first_indexed | 2024-09-23T09:08:14Z |
| format | Article |
| id | mit-1721.1/133015 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T09:08:14Z |
| publishDate | 2021 |
| publisher | BioMed Central |
| record_format | dspace |
| spelling | mit-1721.1/1330152024-06-06T13:45:19Z Gut bacterial metabolites modulate endoplasmic reticulum stress Ke, Xiaobo You, Kwontae Pichaud, Matthieu Haiser, Henry J. Graham, Daniel B. Vlamakis, Hera Porter, Jeffrey A. Xavier, Ramnik J. Massachusetts Institute of Technology. Center for Microbiome Informatics and Therapeutics Background The endoplasmic reticulum (ER) is a membranous organelle that maintains proteostasis and cellular homeostasis, controlling the fine balance between health and disease. Dysregulation of the ER stress response has been implicated in intestinal inflammation associated with inflammatory bowel disease (IBD), a chronic condition characterized by changes to the mucosa and alteration of the gut microbiota. While the microbiota and microbially derived metabolites have also been implicated in ER stress, examples of this connection remain limited to a few observations from pathogenic bacteria. Furthermore, the mechanisms underlying the effects of bacterial metabolites on ER stress signaling have not been well established. Results Utilizing an XBP1s-GFP knock-in reporter colorectal epithelial cell line, we screened 399 microbiome-related metabolites for ER stress pathway modulation. We find both ER stress response inducers (acylated dipeptide aldehydes and bisindole methane derivatives) and suppressors (soraphen A) and characterize their activities on ER stress gene transcription and translation. We further demonstrate that these molecules modulate the ER stress pathway through protease inhibition or lipid metabolism interference. Conclusions Our study identified novel links between classes of gut microbe-derived metabolites and the ER stress response, suggesting the potential for these metabolites to contribute to gut ER homeostasis and providing insight into the molecular mechanisms by which gut microbes impact intestinal epithelial cell homeostasis. 2021-10-18T13:47:35Z 2021-10-18T13:47:35Z 2021-10 2020-08 2021-10-17T03:14:46Z Article http://purl.org/eprint/type/JournalArticle 1474-760X https://hdl.handle.net/1721.1/133015 Ke, X., You, K., Pichaud, M. et al. Gut bacterial metabolites modulate endoplasmic reticulum stress. Genome Biol 22, 292 (2021) en https://doi.org/10.1186/s13059-021-02496-8 Genome Biology Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/ The Author(s) application/pdf BioMed Central BioMed Central |
| spellingShingle | Ke, Xiaobo You, Kwontae Pichaud, Matthieu Haiser, Henry J. Graham, Daniel B. Vlamakis, Hera Porter, Jeffrey A. Xavier, Ramnik J. Gut bacterial metabolites modulate endoplasmic reticulum stress |
| title | Gut bacterial metabolites modulate endoplasmic reticulum stress |
| title_full | Gut bacterial metabolites modulate endoplasmic reticulum stress |
| title_fullStr | Gut bacterial metabolites modulate endoplasmic reticulum stress |
| title_full_unstemmed | Gut bacterial metabolites modulate endoplasmic reticulum stress |
| title_short | Gut bacterial metabolites modulate endoplasmic reticulum stress |
| title_sort | gut bacterial metabolites modulate endoplasmic reticulum stress |
| url | https://hdl.handle.net/1721.1/133015 |
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