Inflammatory bowel disease is a significant public health issue in America. This gut disease is also a risk factor for the initiation and development of colon cancer. As an anti-inflammatory botanical, American ginseng has been shown to play a role in suppressing colitis, reducing inflammation, and preventing cancer. However, the effects of ginseng on the enteric microbiome and on specific molecular profiles have yet to be explored. Using an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced gut inflammation and tumorigenesis mouse model, the effects of oral American ginseng (15 and 30 mg/kg/day) on colitis and colon cancer were determined. After the establishment of a 16S rRNA illumina library from fecal samples, MiSeq sequencing was carried out to reveal the microbial population. A metabolomic analysis was conducted to detect endogenous metabolite changes for potential biomarkers. The results showed that in the acute phase, chemically-induced colitis was significantly reduced by ginseng in a dose-dependent manner, which was supported by histology evaluation. In the chronic phase, obvious colon carcinogenesis was observed in the model group. Ginseng treatment significantly reduced colon tumor multiplicity, which was consistent with pro-inflammatory cytokine level changes. For the fecal microbial communities, greater colitis severity was negatively associated with alpha diversity. With beta diversity, AOM/DSS induced an obvious separation between the control and model groups; however, the plots of the ginseng treatment group were very close to those of the untreated control group. Chemically induced colitis and colon tumorigenesis were correlated with an augment of Bacteroidaceae and Porphyromonadaceae, while the proportion of these families was diminished by ginseng treatment. Our results suggest that the colon cancer preventive effects of ginseng are mediated through an enteric microbiome population-shift recovery and dysbiosis restoration. In both acute and chronic phases, serum metabolomic analysis showed that the plots of the model group were clearly separated from the normal control group, while ginseng treatment, especially in high-dose group, pushed the plots back towards the control group. Compared to model group, ginseng treatment appeared to restore the levels of the observed key endogenous metabolites including glutamine, 6-P-glucose, EPA and oleic acid, which were related to inflammatory responses and energy balance regulations. In summary, we used a platform combining metabolomic and microbiome data to interpret the efficacies of ginseng. With further verification, microbiome profiles and selective endogenous small molecules could be used as biomarkers to elucidate the effects of American ginseng on colitis-associated colon cancer. (This work was supported in part by the NIH/NCCAM grants AT004418 and AT005362).

Citation Format: Chong-Zhi Wang, Haiqiang Yao, Jin-Yi Wan, Jinxiang Zeng, Clara Sava-Segal, Chun-Su Yuan. Gut microbiome and metabolomic profiling reveal preventive effects of American ginseng on inflammation-associated colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1248.