Fucoxanthin Ameliorates Sepsis via Modulating Microbiota by Targeting IRF3 Activation

Area of Science:

• Microbiology
• Immunology
• Pharmacology

Background:

• Sepsis involves exaggerated inflammatory responses, impacting patient survival.
• Fucoxanthin (FX), a carotenoid, suppresses inflammation via IRF3 activation, reducing sepsis mortality in mice.
• The impact of FX-targeted IRF3 on gut microbiota and sepsis mechanisms requires further investigation.

Purpose of the Study:

• To determine how FX-targeted IRF3 modulates intestinal microbiota composition during sepsis.
• To elucidate the mechanisms by which FX influences sepsis development.
• To explore the link between gut microbiota, inflammation, and FX treatment in sepsis.

Main Methods:

• Cecal ligation and puncture (CLP) model in mice to induce sepsis.
• Analysis of bacterial load, short-chain fatty acid (SCFA) levels, and intestinal microbiota composition.
• Correlation analysis between bacterial abundance, SCFA production, and pro-inflammatory cytokines (IL-6, IL-1β, TNF-α).

Main Results:

• FX treatment significantly reduced bacterial load in the abdominal cavity via IRF3 activation.
• FX increased intestinal levels of beneficial SCFAs, acetic and propionic acids.
• FX altered gut microbiota, increasing beneficial Verrucomicrobiota and Akkermansia spp. while decreasing harmful Morganella spp.
• Positive correlations were observed between harmful bacteria (Morganella, Proteus, Escherichia, Klebsiella) and pro-inflammatory cytokines.
• These harmful bacteria negatively correlated with SCFA production.

Conclusions:

• FX alters microbial diversity and promotes SCFA production in a mouse model of sepsis.
• FX reshapes gut homeostasis by modulating the gut microbiota and reducing inflammation.
• These findings support the therapeutic potential of Fucoxanthin for sepsis treatment.