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Antidepressant fluoxetine alleviates colitis by reshaping intestinal microenvironment.

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Title: Antidepressant fluoxetine alleviates colitis by reshaping intestinal microenvironment.
Authors: Teng, Shuo1,2 (AUTHOR), Yang, Yi1 (AUTHOR), Zhang, Wanru1 (AUTHOR), Li, Xiangji1 (AUTHOR), Li, Wenkun1 (AUTHOR), Cui, Zilu1 (AUTHOR), Min, Li1 (AUTHOR) minli@ccmu.edu.cn, Wu, Jing1 (AUTHOR) wujing36youyi@ccmu.edu.cn
Source: Cell Communication & Signaling. 3/12/2024, Vol. 22 Issue 1, p1-15. 15p.
Subject Terms: *INFLAMMATORY bowel diseases, *FLUOXETINE, *RNA sequencing, *COLITIS, *ANTIDEPRESSANTS, *INTESTINES
Abstract: Background: The impact of antidepressants on Inflammatory bowel diseases (IBD) has been extensively studied. However, the biological effects and molecular mechanisms of antidepressants in alleviating colitis remain unclear. Methods: We systematically assessed how antidepressants (fluoxetine, fluvoxamine and venlafaxine) affected IBD and chose fluoxetine, the most effective one, for mechanism studies. We treated the C56BL/6 mice of the IBD model with fluoxetine and their controls. We initially assessed the severity of intestinal inflammation in mice by body weight loss, disease Activity Index scores and the length of the colon. The H&E staining and immunohistochemical staining of MUC2 of colon sections were performed to observe the pathological changes. RT-qPCR and western blot were conducted to assess the expression level of the barrier and inflammation-associated genes. Then, single-cell RNA sequencing was performed on mouse intestinal mucosa. Seurat was used to visualize the data. Uniform Manifold Approximation and Projection (UMAP) was used to perform the dimensionality reduction. Cell Chat package was used to perform cell–cell communication analysis. Monocle was used to conduct developmental pseudotime analysis. Last, RT-qPCR, western blot and immunofluorescence staining were conducted to test the phenomenon discovered by single-cell RNA sequencing in vitro. Results: We found that fluoxetine treatment significantly alleviated colon inflammation. Notably, single-cell RNA sequencing analysis revealed that fluoxetine affected the distribution of different cell clusters, cell–cell communication and KEGG pathway enrichment. Under the treatment of fluoxetine, enterocytes, Goblet cells and stem cells became the dominating cells. The pseudotime analysis showed that there was a trend for M1 macrophages to differentiate into M2 macrophages. Lastly, we tested this phenomenon in vitro, which exhibited anti-inflammatory effects on enterocytes. Conclusions: Fluoxetine exhibited anti-inflammatory effects on intestinal mucosa via remodeling of the intestinal cells and macrophages, which reveals that fluoxetine is a promising therapeutic drug for the treatment of IBD and psychiatric comorbidities. [ABSTRACT FROM AUTHOR]
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  Data: Antidepressant fluoxetine alleviates colitis by reshaping intestinal microenvironment.
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  Data: <searchLink fieldCode="AR" term="%22Teng%2C+Shuo%22">Teng, Shuo</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yang%2C+Yi%22">Yang, Yi</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhang%2C+Wanru%22">Zhang, Wanru</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Xiangji%22">Li, Xiangji</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Wenkun%22">Li, Wenkun</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Cui%2C+Zilu%22">Cui, Zilu</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Min%2C+Li%22">Min, Li</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> minli@ccmu.edu.cn</i><br /><searchLink fieldCode="AR" term="%22Wu%2C+Jing%22">Wu, Jing</searchLink><relatesTo>1</relatesTo> (AUTHOR)<i> wujing36youyi@ccmu.edu.cn</i>
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  Data: <searchLink fieldCode="JN" term="%22Cell+Communication+%26+Signaling%22">Cell Communication & Signaling</searchLink>. 3/12/2024, Vol. 22 Issue 1, p1-15. 15p.
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  Data: *<searchLink fieldCode="DE" term="%22INFLAMMATORY+bowel+diseases%22">INFLAMMATORY bowel diseases</searchLink><br />*<searchLink fieldCode="DE" term="%22FLUOXETINE%22">FLUOXETINE</searchLink><br />*<searchLink fieldCode="DE" term="%22RNA+sequencing%22">RNA sequencing</searchLink><br />*<searchLink fieldCode="DE" term="%22COLITIS%22">COLITIS</searchLink><br />*<searchLink fieldCode="DE" term="%22ANTIDEPRESSANTS%22">ANTIDEPRESSANTS</searchLink><br />*<searchLink fieldCode="DE" term="%22INTESTINES%22">INTESTINES</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: The impact of antidepressants on Inflammatory bowel diseases (IBD) has been extensively studied. However, the biological effects and molecular mechanisms of antidepressants in alleviating colitis remain unclear. Methods: We systematically assessed how antidepressants (fluoxetine, fluvoxamine and venlafaxine) affected IBD and chose fluoxetine, the most effective one, for mechanism studies. We treated the C56BL/6 mice of the IBD model with fluoxetine and their controls. We initially assessed the severity of intestinal inflammation in mice by body weight loss, disease Activity Index scores and the length of the colon. The H&E staining and immunohistochemical staining of MUC2 of colon sections were performed to observe the pathological changes. RT-qPCR and western blot were conducted to assess the expression level of the barrier and inflammation-associated genes. Then, single-cell RNA sequencing was performed on mouse intestinal mucosa. Seurat was used to visualize the data. Uniform Manifold Approximation and Projection (UMAP) was used to perform the dimensionality reduction. Cell Chat package was used to perform cell–cell communication analysis. Monocle was used to conduct developmental pseudotime analysis. Last, RT-qPCR, western blot and immunofluorescence staining were conducted to test the phenomenon discovered by single-cell RNA sequencing in vitro. Results: We found that fluoxetine treatment significantly alleviated colon inflammation. Notably, single-cell RNA sequencing analysis revealed that fluoxetine affected the distribution of different cell clusters, cell–cell communication and KEGG pathway enrichment. Under the treatment of fluoxetine, enterocytes, Goblet cells and stem cells became the dominating cells. The pseudotime analysis showed that there was a trend for M1 macrophages to differentiate into M2 macrophages. Lastly, we tested this phenomenon in vitro, which exhibited anti-inflammatory effects on enterocytes. Conclusions: Fluoxetine exhibited anti-inflammatory effects on intestinal mucosa via remodeling of the intestinal cells and macrophages, which reveals that fluoxetine is a promising therapeutic drug for the treatment of IBD and psychiatric comorbidities. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Cell Communication & Signaling is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1186/s12964-024-01538-5
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              Text: 3/12/2024
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