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Author ORCID Identifier

https://orcid.org/0000-0002-9889-0069

AccessType

Campus-Only Access for Five (5) Years

Document Type

dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Food Science

Month Degree Awarded

September

First Advisor

Hang Xiao

Subject Categories

Food Biotechnology

Abstract

Curcumin is a widely studied bioactive food component for its anti-inflammatory effects. Herein, we determined the effects of curcumin on gut microbiota and their implication in anti-colonic inflammation in mice with colitis induced by dextran sodium sulfate (DSS). The results demonstrated that DSS treatment drastically altered the composition of gut microbiota in mice, which was associated with the development of colitis. Furthermore, curcumin alleviated the symptoms of colitis and decreased the expression levels of pro-inflammatory cytokines such as INF-g, IL-1β, IL-6 and TNF-α, in the colon of DSS-treated mice. Our results demonstrated that in the GI tract curcumin underwent phase I metabolism to yield three metabolites and two broken down products, namely tetrahydro-curcumin (THC), hexahydro-curcumin (HHC), octahydro-curcumin (OHC), ferulic acid (FA), and dihydroferulic acid (DFA). Curcumin, phase I metabolites, FA, and DFA then were subject to phase II metabolism to yield their corresponding conjugated phase II metabolites. In addition, fecal bacteria were able to transform curcumin to yield phase I metabolites, and they can further breakdown these four compounds to yield fission products such as ferulic acid and dihydroferulic acid. Further, the human trial study showed the composition of curcumin and its metabolites in feces, and the human fecal bacteria also can bio-transform curcumin to phase I metabolites, DAF, and FA. Overall, our results demonstrated that composition of gut microbiota had a profound impact on the biotransformation of curcumin in the colon, which might have a significant influence on the health effects of dietary curcumin, especially in the colon. The results showed that curcumin showed a dose-dependent inhibition on the production of nitric oxide (NO) induced by LPS in the macrophages, while the mixture of four metabolites did not significantly inhibit NO production. However, the combination of curcumin and the metabolites showed much stronger inhibitory effects than that of curcumin or the metabolite mixture alone. More importantly, the isobologram analysis confirmed that the enhanced anti-inflammatory effects of the combination of curcumin and the metabolites were highly synergistic.

DOI

https://doi.org/10.7275/24280057

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