Inhibitory Effects of Nobiletin on Colitis were Associated with Altered Gut Microbiota

Abstract

Understanding how dietary compounds such as nobiletin alter the colonic environment is critical in studying their roles in modulating gut health and gut associated diseases. In this study, we determined the effects of dietary nobiletin treatment on dextran sodium sulfate (DSS)‐induced colitis as well as the composition of gut microbiota in mice. The results revealed that nobiletin treatment significantly decreased the severity of colonic inflammation in DSS‐treated mice, evidenced by the reduced production of pro‐inflammatory cytokines (i.e., GM‐CSF, INF‐γ, IL‐1β, IL‐2, IL‐6, KC/GRO, and TNF‐α) in the colonic mucosa, increased colon length, and decreased disease activity index and histologic score of inflammation (p<0.05) by the nobiletin treatment. Results from next generation sequencing of the fecal microbiota showed that DSS treatment significantly altered the microbial structure of fecal microbiota in mice, and dietary nobiletin treatment tend to reverse these alterations. It was also demonstrated that DSS treatment decreased the abundance of Bifidobacterium and Lactobacillus compared to the negative control (healthy) mice. Nobiletin treatment partially reversed the DSS‐induced decrease in these two genera in DSS treated mice. It is noteworthy that nobiletin had no effect on Bifidobacterium, but increased the abundance of Lactobacillus in the healthy mice (non‐DSS treated). DSS treatment significantly increased the abundance of Sutterella and Bilophila, while nobiletin effectively reversed DSS‐induced increases in these two genera. Overall, our results for the first time suggested that modification of gut microbiota by dietary nobiletin might contribute to its inhibitory effects against the development of colitis in mice.