Anti-colitis benefits of ellagic acid-Fucus vesiculosus polysaccharide solid dispersions by regulating intestinal microbiota dysfunction in mice

The current study was aimed to investigate the anti-inflammatory effects and potential mechanisms of ellagic acid- Fucus vesiculosus polysaccharide solid dispersion (EA/FVP SD) based on lipopolysaccharide (LPS)-induced inflammatory cell and dextran sulfate sodium (DSS)-induced colitis mice models. The cell experiment showed that EA/FVP SD possessed a better in vitro anti-inflammatory activity than EA or FVP alone. Further colitis mice experiments showed that EA/FVP SD administration significantly ameliorated symptoms in colitis mice by reversing the weight loss, reducing the disease activity index (DAI) scores, maintaining the colon length and decreasing the levels of pro-inflammatory factors (such as TNF- α , IL-6, and IL-1 β ). Immunofluorescent staining suggested that the anti-inflammatory activity was related to the down-regulation of CD11b and F4/80 protein expression levels. Notedly, high dose EA/FVP SD exhibited the best performance in reducing the fluorescence intensity. Moreover, microbiome analysis indicated that EA/FVP SD administration could reverse the abnormal bacteria composition changes and enhance the intestinal barrier function. Metabolomic profiling suggested the alterations of EA/FVP SD in key metabolic pathways, including linoleic acid metabolism, sphingolipid metabolism, necroptosis/apoptosis-related processes, and FoxO signaling pathway, which may be associated with changes in gut microbiota. These findings support EA/FVP SD as a candidate adjuvant strategy for colitis management, while further pharmacokinetic and pathway-validation studies are still needed.