Fucoidan alleviated DSS-induced colitis, reshaped the gut microbiota, and was associated with microbiota-dependent accumulation of citraconic acid, which itself reduced colitis severity and ferroptosis-related oxidative stress through enhanced Nrf2 antioxidant responses and restored SLC7A11 and GPX4 expression.
Fucoidan alleviated colonic injury and improved epithelial barrier integrity in DSS-induced colitis.
Fucoidan reshaped the gut microbial profile, reducing Pseudomonadota and enriching beneficial taxa.
Targeted metabolomics identified citraconic acid (CA) as a candidate metabolite associated with fucoidan-mediated protection.
Fucoidan-associated CA accumulation was partially dependent on the gut microbiota.
CA administration reduced colitis severity and improved barrier function while attenuating ferroptosis-related oxidative stress.
In vitro, CA reduced mitochondrial Fe2+ accumulation and lipid peroxidation and enhanced tight junction protein expression.
The authors conclude that a microbiota-associated metabolic mechanism underlies fucoidan's intestinal protection, with CA as a potential mediator of its anti-inflammatory activity.
This study looked at how fucoidan, a compound from brown seaweed, protects the gut in a mouse model of colitis (intestinal inflammation) induced by a chemical called DSS. Fucoidan reduced damage to the colon, helped maintain the gut lining's barrier, and shifted the gut bacteria, including lowering a group of bacteria called Pseudomonadota and increasing beneficial types. The researchers then searched for chemicals made in the gut that might explain this protection and found one called citraconic acid. When gut bacteria were wiped out with antibiotics, fucoidan's effect on citraconic acid was partly reduced, suggesting that the bacteria help produce or maintain it. Giving citraconic acid itself reduced colitis severity. It also reduced a form of cell damage called ferroptosis, which involves iron-driven oxidative damage. It did so by boosting the cell's antioxidant defenses (Nrf2) and restoring two protective proteins, SLC7A11 and GPX4. In lab-grown cells, citraconic acid lowered iron buildup in mitochondria and fat damage, and increased proteins that seal gaps between gut cells. This research suggests that fucoidan's gut benefits may work partly through gut bacteria and the small molecules they influence. The findings come from mice and cell experiments, and the abstract describes citraconic acid as a candidate or potential mediator, so they do not show that fucoidan or citraconic acid would help people with inflammatory bowel conditions.
Wei Y, Ren X, Song S, Ai C. (2026). Fucoidan Alleviates Intestinal Inflammation through Microbiota-Associated Citraconic Acid Accumulation to Modulate Ferroptosis-Related Pathways.. Journal of agricultural and food chemistry. https://doi.org/10.1021/acs.jafc.6c08698