Vitamin D Modified DSS-Induced Colitis in Mice via STING Signaling Pathway

Although the underlying mechanisms are not yet fully understood, vitamin D has been proven to be associated with the pathogenesis of inflammatory bowel disease, participating in immune response and regulating gut microbiota composition. In this study, we established a dextran sodium sulfate-induced...

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Main Authors: Zhihao Wu, Baohua Ma, Min Xiao, Qian Ren, Yanhua Shen, Zhengyu Zhou
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/14/6/715
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author Zhihao Wu
Baohua Ma
Min Xiao
Qian Ren
Yanhua Shen
Zhengyu Zhou
author_facet Zhihao Wu
Baohua Ma
Min Xiao
Qian Ren
Yanhua Shen
Zhengyu Zhou
author_sort Zhihao Wu
collection DOAJ
description Although the underlying mechanisms are not yet fully understood, vitamin D has been proven to be associated with the pathogenesis of inflammatory bowel disease, participating in immune response and regulating gut microbiota composition. In this study, we established a dextran sodium sulfate-induced colitis model and intervened with vitamin D. Subsequently, colonic histopathology, serum biochemistry, transcription of inflammatory cytokines, gut microbiota, and key signaling pathways were examined. Our research demonstrated that intervention with vitamin D reduced the disease activity index of DSS-induced colitis and improved histopathological changes, protecting tight junction protein ZO-1 and intestinal glands from damage induced by DSS. Analysis of gut microbiota revealed alterations in both α diversity and β diversity in DSS-induced colitis, whereas interventions with active vitamin D corrected the changes in certain bacterial abundance and improved the composition of gut microbiota. The transcription levels of inflammatory cytokines, including <i>IL-23</i>, <i>IL-1β</i>, <i>IFN</i>-γ, <i>IL-6</i>, <i>IL-17</i>, and <i>STING</i>, were elevated in the DSS-induced colitis model. However, intervention with active vitamin D effectively suppressed the transcription of these factors. Finally, immunohistochemistry and Western blotting revealed that the intervention with vitamin D suppressed the expression of proteins associated with the STING pathway, including GATA1, STING, IRF3, and IKBα, leading to inhibition of downstream IFN-β production. Vitamin D administration can ameliorate the severity of DSS-induced colitis by preserving intestinal barrier integrity, modulating gut microbiota composition through suppression of the STING pathway.
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spelling doaj-art-4fed4faba1ad4cbe98c1b9d4298bad3e2025-08-20T03:32:28ZengMDPI AGBiology2079-77372025-06-0114671510.3390/biology14060715Vitamin D Modified DSS-Induced Colitis in Mice via STING Signaling PathwayZhihao Wu0Baohua Ma1Min Xiao2Qian Ren3Yanhua Shen4Zhengyu Zhou5Laboratory Animal Center, Suzhou Medical College, Soochow University, Suzhou 215123, ChinaLaboratory Animal Center, Suzhou Medical College, Soochow University, Suzhou 215123, ChinaLaboratory Animal Center, Suzhou Medical College, Soochow University, Suzhou 215123, ChinaLaboratory Animal Center, Suzhou Medical College, Soochow University, Suzhou 215123, ChinaLaboratory Animal Center, Suzhou Medical College, Soochow University, Suzhou 215123, ChinaLaboratory Animal Center, Suzhou Medical College, Soochow University, Suzhou 215123, ChinaAlthough the underlying mechanisms are not yet fully understood, vitamin D has been proven to be associated with the pathogenesis of inflammatory bowel disease, participating in immune response and regulating gut microbiota composition. In this study, we established a dextran sodium sulfate-induced colitis model and intervened with vitamin D. Subsequently, colonic histopathology, serum biochemistry, transcription of inflammatory cytokines, gut microbiota, and key signaling pathways were examined. Our research demonstrated that intervention with vitamin D reduced the disease activity index of DSS-induced colitis and improved histopathological changes, protecting tight junction protein ZO-1 and intestinal glands from damage induced by DSS. Analysis of gut microbiota revealed alterations in both α diversity and β diversity in DSS-induced colitis, whereas interventions with active vitamin D corrected the changes in certain bacterial abundance and improved the composition of gut microbiota. The transcription levels of inflammatory cytokines, including <i>IL-23</i>, <i>IL-1β</i>, <i>IFN</i>-γ, <i>IL-6</i>, <i>IL-17</i>, and <i>STING</i>, were elevated in the DSS-induced colitis model. However, intervention with active vitamin D effectively suppressed the transcription of these factors. Finally, immunohistochemistry and Western blotting revealed that the intervention with vitamin D suppressed the expression of proteins associated with the STING pathway, including GATA1, STING, IRF3, and IKBα, leading to inhibition of downstream IFN-β production. Vitamin D administration can ameliorate the severity of DSS-induced colitis by preserving intestinal barrier integrity, modulating gut microbiota composition through suppression of the STING pathway.https://www.mdpi.com/2079-7737/14/6/7151,25(OH)<sub>2</sub>D<sub>3</sub>DSS-induced colitisSTING pathwaygut microbiotainflammatory bowel disease
spellingShingle Zhihao Wu
Baohua Ma
Min Xiao
Qian Ren
Yanhua Shen
Zhengyu Zhou
Vitamin D Modified DSS-Induced Colitis in Mice via STING Signaling Pathway
Biology
1,25(OH)<sub>2</sub>D<sub>3</sub>
DSS-induced colitis
STING pathway
gut microbiota
inflammatory bowel disease
title Vitamin D Modified DSS-Induced Colitis in Mice via STING Signaling Pathway
title_full Vitamin D Modified DSS-Induced Colitis in Mice via STING Signaling Pathway
title_fullStr Vitamin D Modified DSS-Induced Colitis in Mice via STING Signaling Pathway
title_full_unstemmed Vitamin D Modified DSS-Induced Colitis in Mice via STING Signaling Pathway
title_short Vitamin D Modified DSS-Induced Colitis in Mice via STING Signaling Pathway
title_sort vitamin d modified dss induced colitis in mice via sting signaling pathway
topic 1,25(OH)<sub>2</sub>D<sub>3</sub>
DSS-induced colitis
STING pathway
gut microbiota
inflammatory bowel disease
url https://www.mdpi.com/2079-7737/14/6/715
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AT qianren vitamindmodifieddssinducedcolitisinmiceviastingsignalingpathway
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