Fucoxanthin Ameliorates Sepsis via Modulating Microbiota by Targeting IRF3 Activation
To improve patient survival in sepsis, it is necessary to curtail exaggerated inflammatory responses. Fucoxanthin (FX), a carotenoid derived from brown algae, efficiently suppresses pro-inflammatory cytokine expression via IRF3 activation, thereby reducing mortality in a mouse model of sepsis. Howev...
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MDPI AG
2023-09-01
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Series: | International Journal of Molecular Sciences |
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author | Jingqian Su Biyun Guan Qiaofen Su Shan Hu Shun Wu Zhiyong Tong Fen Zhou |
author_facet | Jingqian Su Biyun Guan Qiaofen Su Shan Hu Shun Wu Zhiyong Tong Fen Zhou |
author_sort | Jingqian Su |
collection | DOAJ |
description | To improve patient survival in sepsis, it is necessary to curtail exaggerated inflammatory responses. Fucoxanthin (FX), a carotenoid derived from brown algae, efficiently suppresses pro-inflammatory cytokine expression via IRF3 activation, thereby reducing mortality in a mouse model of sepsis. However, the effects of FX-targeted IRF3 on the bacterial flora (which is disrupted in sepsis) and the mechanisms by which it impacts sepsis development remain unclear. This study aims to elucidate how FX-targeted IRF3 modulates intestinal microbiota compositions, influencing sepsis development. FX significantly reduced the bacterial load in the abdominal cavity of mice with cecal ligation and puncture (CLP)-induced sepsis via IRF3 activation and increased short-chain fatty acids, like acetic and propionic acids, with respect to their intestines. FX also altered the structure of the intestinal flora, notably elevating beneficial Verrucomicrobiota and <i>Akkermansia</i> spp. while reducing harmful <i>Morganella</i> spp. Investigating the inflammation–flora link, we found positive correlations between the abundances of <i>Morganella</i> spp., <i>Proteus</i> spp., <i>Escherichia</i> spp., and <i>Klebsiella</i> spp. and pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) induced by CLP. These bacteria were negatively correlated with acetic and propionic acid production. FX alters microbial diversity and promotes short-chain fatty acid production in mice with CLP-induced sepsis, reshaping gut homeostasis. These findings support the value of FX for the treatment of sepsis. |
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spelling | doaj.art-633cee1faae6489f995a1f6a3a899be22023-11-19T11:03:20ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124181380310.3390/ijms241813803Fucoxanthin Ameliorates Sepsis via Modulating Microbiota by Targeting IRF3 ActivationJingqian Su0Biyun Guan1Qiaofen Su2Shan Hu3Shun Wu4Zhiyong Tong5Fen Zhou6Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou 350117, ChinaFujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou 350117, ChinaFujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou 350117, ChinaFujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou 350117, ChinaFujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou 350117, ChinaFujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou 350117, ChinaFujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou 350117, ChinaTo improve patient survival in sepsis, it is necessary to curtail exaggerated inflammatory responses. Fucoxanthin (FX), a carotenoid derived from brown algae, efficiently suppresses pro-inflammatory cytokine expression via IRF3 activation, thereby reducing mortality in a mouse model of sepsis. However, the effects of FX-targeted IRF3 on the bacterial flora (which is disrupted in sepsis) and the mechanisms by which it impacts sepsis development remain unclear. This study aims to elucidate how FX-targeted IRF3 modulates intestinal microbiota compositions, influencing sepsis development. FX significantly reduced the bacterial load in the abdominal cavity of mice with cecal ligation and puncture (CLP)-induced sepsis via IRF3 activation and increased short-chain fatty acids, like acetic and propionic acids, with respect to their intestines. FX also altered the structure of the intestinal flora, notably elevating beneficial Verrucomicrobiota and <i>Akkermansia</i> spp. while reducing harmful <i>Morganella</i> spp. Investigating the inflammation–flora link, we found positive correlations between the abundances of <i>Morganella</i> spp., <i>Proteus</i> spp., <i>Escherichia</i> spp., and <i>Klebsiella</i> spp. and pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) induced by CLP. These bacteria were negatively correlated with acetic and propionic acid production. FX alters microbial diversity and promotes short-chain fatty acid production in mice with CLP-induced sepsis, reshaping gut homeostasis. These findings support the value of FX for the treatment of sepsis.https://www.mdpi.com/1422-0067/24/18/13803sepsisaloe emodininflammationcecal ligation puncturegut microbiota |
spellingShingle | Jingqian Su Biyun Guan Qiaofen Su Shan Hu Shun Wu Zhiyong Tong Fen Zhou Fucoxanthin Ameliorates Sepsis via Modulating Microbiota by Targeting IRF3 Activation International Journal of Molecular Sciences sepsis aloe emodin inflammation cecal ligation puncture gut microbiota |
title | Fucoxanthin Ameliorates Sepsis via Modulating Microbiota by Targeting IRF3 Activation |
title_full | Fucoxanthin Ameliorates Sepsis via Modulating Microbiota by Targeting IRF3 Activation |
title_fullStr | Fucoxanthin Ameliorates Sepsis via Modulating Microbiota by Targeting IRF3 Activation |
title_full_unstemmed | Fucoxanthin Ameliorates Sepsis via Modulating Microbiota by Targeting IRF3 Activation |
title_short | Fucoxanthin Ameliorates Sepsis via Modulating Microbiota by Targeting IRF3 Activation |
title_sort | fucoxanthin ameliorates sepsis via modulating microbiota by targeting irf3 activation |
topic | sepsis aloe emodin inflammation cecal ligation puncture gut microbiota |
url | https://www.mdpi.com/1422-0067/24/18/13803 |
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