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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/18/13803 |
| Summary: | 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. |
|---|---|
| ISSN: | 1661-6596 1422-0067 |