Lee P.-SNagabhushanam KHo C.-TMIN-HSIUNG PAN2022-04-252022-04-25202116134125https://www.scopus.com/inward/record.uri?eid=2-s2.0-85110294087&doi=10.1002%2fmnfr.202100410&partnerID=40&md5=1c72004e5788df13f0d5ed7d0a6bd99bhttps://scholars.lib.ntu.edu.tw/handle/123456789/606143Scope: Epidemiological studies show a consistent and compelling association between the risk of colorectal cancer development and obesity, but its mechanisms remain poorly understood. Evidence is mounting that colorectal cancer can be prevented by nutritional supplements, such as phytochemicals. Garcinol, a polyisoprenylated benzophenone derivative, is widely present in Garcinia plants. This study investigates the potential role of garcinol supplementation in ameliorating obesity-induced colon cancer development. Methods and Results: An animal model to investigate the effect of high-fat-diet (HFD)-induced obesity on promoting colitis-associated colon cancer (AOM (azoxymethane)/DSS (dextran sodium sulfate)-induced) is designed. The results show that HFD can promote colitis-associated colon cancer as compared to an AOM/DSS group without the intervention of obesity, and supplementing with 0.05% garcinol in the diet can significantly ameliorate obesity-promoted colon carcinogenesis. The results also reveals that the microbiota composition of each group is significantly different and clustered. The most representative genera are Alistipes, Romboutsia, and Ruminococcus. The RNA-sequencing results show that the administration of garcinol can regulate genes and improve obesity-promoting colitis-associated colon carcinogenesis. Conclusion: The study results suggest that garcinol can prevent obesity-promoted colorectal cancer, and these findings provide important niches for the future development of garcinol as functional foods or adjuvant therapeutic agents. ? 2021 Wiley-VCH GmbHcolorectal cancergarcinolmicrobiotaobesityRNA-sequencingantineoplastic agentazoxymethanebiological markercyclinecytokinedextran sulfatelipidterpeneadverse eventanimalbloodC57BL mousecell proliferationcolitiscolon tumorcomplicationdisease modeldrug effectdysbiosisgene expression regulationintestine floralipid dietmalemetabolismorgan sizepathologyphysiologyAnimalsAnticarcinogenic AgentsAzoxymethaneBiomarkersCell ProliferationColitisColonic NeoplasmsCytokinesDextran SulfateDiet, High-FatDisease Models, AnimalDysbiosisGastrointestinal MicrobiomeGene Expression Regulation, NeoplasticLipidsMaleMice, Inbred C57BLObesityOrgan SizeProliferating Cell Nuclear AntigenTerpenes[SDGs]SDG2[SDGs]SDG3journal article10.1002/mnfr.202100410342452242-s2.0-85110294087