(P03-042-23) Anti-Inflammatory and Intestinal Microbiota Regulation of Eisenia bicyclis in Ulcerative Colitis

Objectives: Ulcerative colitis (UC) is a chronic condition characterized by dysbiosis of intestinal flora, inflammation and ulceration of intestinal tissues. Eisenia bicyclis is a phlorotannin-rich brown alga with the potential to prevent ulcerative colitis by reducing inflammation via inhibition of mTOR and NF-κB and regulating intestinal flora.

Methods: In this work, the preventive ability and potential mechanism of Eisenia bicyclis 70% ethanol extract (EB) against UC in vitro and in vivo were investigated. Experiments In vitro included the cultivation of RAW264.7 and Caco-2 cells, and their co-culture system, and LPS was employed to induce cell inflammatory response. A mouse model of colitis performed In vivo by EB dosage for 4 weeks and DSS administration in the final week. Experimental methods include MTT, ELISA, PCR, western blotting, and 16s Sequencing.

Results: LC-MS results indicated that the principal phenolic active substances in EB were dioxinodehydroeckol, hydroxyhexafuhalol, quercetin, rutin, diatoxanthin, and tetraphlorethol. EB strongly inhibited the release of TNF-α and IL-6, as well as the mRNA expression of Nfkb, Pi3k, Akt1, Mtor and S6k and the phosphorylation of mTOR axis-related proteins in inflammatory RAW264.7 and Caco-2 cells. In a co-culture system, EB significantly ameliorated LPS-induced decreases in the expression of tight junction mRNA and TEER values. In vivo, the consumption of EB improved intestine length, spleen enlargement, histological scores, and the DAI index. Compared to the DSS control, EB intake decreased Nfkb, Cox-2, Zo1, claudin, and Mtor axis-related gene expressions as well as MPO, lipocalin-2, TNF-α, IL-6, and IFN-γ protein expression. In the microbiota analysis, EB intake decreased the Firmicutes/Bacteroidetes ratio and the abundance of pathogenic bacteria Anaerotruncus spp. In addition, Lachnospiraceae, Lactococcus lactis and Bifidobacterium bifidum were elevated by EB intake and negatively correlated with several pathological indicators of colitis.

Conclusions: EB has the potential to reduce intestinal inflammation and modulate gut microbiota. Therefore, the phenolic extract of EB can be utilized as a dietary supplement to prevent the occurrence and development of ulcerative colitis.

Funding Sources: National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT)