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| 標題: | Inhibition of gut microbial β-glucuronidase effectively prevents carcinogen-induced microbial dysbiosis and intestinal tumorigenesis |
| 作者: | Cheng, Kai-Wen
Tseng, Chih-Hua
Chen, I. -Ju
Huang, Bo-Cheng
Liu, Hui-Ju
Ho, Kai-Wen
Lin, Wen-Wei
Chuang, Chih-Hung
Huang, Ming-Yii
Leu, Yu-Lin
Roffler, Steve R.
Wang, Jaw-Yuan
Chen, Yeh-Long
Cheng, Tian-Lu |
| 貢獻者: | California Institute of Technology
Kaohsiung Medical University
Kaohsiung Municipal Ta-Tung Hospital
I Shou University
National Sun Yat Sen University
Department of Pharmacy, Chia Nan University of Pharmacy & Science
Academia Sinica - Taiwan |
| 關鍵字: | colorectal-cancer
colon carcinogenesis
mouse models
sequences
azoxymethane
communities
unifrac
silva
mice
risk |
| 日期: | 2022 |
| 上傳時間: | 2023-12-11 14:04:56 (UTC+8) |
| 出版者: | ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD |
| 摘要: | The bidirectional interaction between carcinogens and gut microbiota that contributes to colorectal cancer is complicated. Reactivation of carcinogen metabolites by microbial beta-glucuronidase (beta G) in the gut potentially plays an important role in colorectal carcinogenesis. We assessed the chemoprotective effects and associated changes in gut microbiota induced by pre-administration of bacterial-specific beta G inhibitor TCH-3511 in carcinogen azoxymethane (AOM)-treated APC(Min/+) mice. AOM induced intestinal beta G activity, which was reflected in increases in the incidence, formation, and number of tumors in the intestine. Notably, inhibition of gut microbial beta G by TCH-3511 significantly reduced AOM-induced intestinal beta G activity, decreased the number of polyps in both the small and large intestine to a frequency that was similar in mice without AOM exposure. AOM also led to lower diversity and altered composition in the gut microbiota with a significant increase in mucindegrading Akkermansia genus. Conversely, mice treated with TCH-3511 and AOM exhibited a more similar gut microbiota structure as mice without AOM administration. Importantly, TCH-3511 treatment significant decreased Akkermansia genus and produced a concomitant increase in short-chain fatty acid butyrate-producing gut commensal microbes Lachnoospiraceae NK4A136 group genus in AOM-treated mice. Taken together, our results reveal a key role of gut microbial beta G in promoting AOM-induced gut microbial dysbiosis and intestinal tumorigenesis, indicating the chemoprotective benefit of gut microbial beta G inhibition against carcinogens via maintaining the gut microbiota balance and preventing cancer-associated gut microbial dysbiosis. Thus, the bacterial-specific beta G inhibitor TCH-3511 is a potential chemoprevention agent for colorectal cancer. |
| 關聯: | PHARMACOLOGICAL RESEARCH, v.177, March 2022, 106115 |
| 顯示於類別: | [藥學系(所)] 期刊論文
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