Role of intestinal microbiome in American ginseng-mediated colon cancer protection in high fat diet-fed AOM/DSS mice
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Chronic intestinal inflammation is a risk factor for colorectal cancer (CRC) initiation and development. Diets that are rich in Western style fats have been shown to promote CRC. This study was conducted to investigate the role of intestinal microbiome in American ginseng-mediated CRC chemoprevention in a mouse model. The population and diversity of enteric microbiome were evaluated after the ginseng treatment.
Using an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced gut inflammation and tumorigenesis mouse model, the effects of oral American ginseng on high fat diet-associated enteric pathology were determined. After establishment of a 16S rRNA illumina library from fecal samples, MiSeq sequencing was carried out to reveal the microbial population. The alpha and beta diversities of microbiome were analyzed.
American ginseng significantly attenuated AOM/DSS-induced colon inflammation and tumorigenesis by reducing the colitis score and colon tumor multiplicity. The MiSeq results showed that the majority of sequences fell into three phyla: Firmicutes, Bacteroidetes and Verrucomicrobia. Further, two significant abundance shifts at the family level, Bacteroidaceae and Porphyromonadaceae, were identified to support ginseng’s anti-colitis and anti-tumor effects. In addition, alpha and beta diversity data demonstrated that ginseng led to a profound recovery from the AOM/DSS-induced dysbiosis in the microbial community.
Our results suggest that the CRC chemopreventive effects of American ginseng are mediated through enteric microbiome population-shift recovery and dysbiosis restoration. Ginseng’s regulation of the microbiome balance contributes to the maintenance of enteric homeostasis.
KeywordsGut inflammation Tumorigenesis Colorectal cancer AOM/DSS American ginseng Intestinal microbiome 16S rRNA MiSeq sequencing Dysbiosis
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Conflict of interest
The authors declare no conflict of interest.
Animals were cared for in the animal facility at the University of Chicago. This facility follows NIH guidelines for the humane care of animals. Use of these animals was approved under the guidelines of the Animal Care and Use Committee and those of the University of Chicago, both of which comply with the guidelines outlined by the National Institutes of Health.
The manuscript does not contain clinical studies or patient data.
This work was supported in part by the grants of NIH AT004418, AT005362, GM120046 and 5P30DK042086.