Evodiamine relieves ulcerative colitis through reinventing the communication of "host-gut microbiota-macrophages".

BACKGROUND AND PURPOSE: Accumulating evidence suggests that Evodiamine (EVO) exerts anti-inflammatory properties in ulcerative colitis (UC). Macrophages serve as driving factors of inflammation and the crosstalk within the "host-gut microbiota-macrophages" is considered essential in the pathogenesis of UC, however the underlying connections and mechanisms involved remained unclear. This study aimed to investigate how EVO modulates macrophages polarization balance in UC model through remodeling of host-microbiota interactions.

METHODS

UC models were induced in zebrafish and C57BL/6J mice through trinitro-benzene-sulfonic acid (TNBS) and dextran sulfate sodium salt (DSS), respectively. The key indicators of intestinal inflammation, macrophage polarization ratio in colon, colon transcriptomics and fecal microbiota were detected. Additionally, fecal microbiota transplantation (FMT) experiment was conducted to determine whether EVO ameliorates UC symptoms by regulating the intestinal microbiota and subsequently influencing M1/M2 macrophage polarization balance.

RESULTS

We found that EVO administration significantly alleviated intestinal tissue damage in both zebrafish and murine models of UC. Additionally, EVO treatment restored the M1/M2 macrophage polarization balance in the intestinal tissue of UC mice, and 16S rRNA analysis indicated that EVO alleviated the intestinal inflammation by modulating the composition of the intestinal microbiota. Furthermore, antibiotics and FMT experiments confirmed that modulation of M1/M2 macrophages polarization balance by EVO was mediated by the intestinal microbiota, potentially through NF-κB/STAT3 and interferon regulatory factor 5 (IRF5) pathway.

CONCLUSIONS

EVO remodeled the communication of "host-gut microbiota-macrophages" by regulating the NF-κB/STAT3 and IRF5 pathway, thereby providing novel perspectives into underling mechanism of EVO in the therapeutic effects against UC.