Genetically Predicted Causal Effects of Gut Microbiota and Gut Metabolites on Digestive Tract Cancer: A Two-Sample Mendelian Randomization Analysis.

Autor:	Li XJ; VIP Department, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.; These authors contributed equally to this work., Gao MG; Department of Clinical Nutrition, Huadu District People's Hospital, Southern Medical University, Guangzhou 510800, China.; These authors contributed equally to this work., Chen XX; VIP Department, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China., Rong YM; VIP Department, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China., Huang LL; VIP Department, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China., Huang JS; VIP Department, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.; State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.; Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
Jazyk:	angličtina
Zdroj:	World journal of oncology [World J Oncol] 2023 Dec; Vol. 14 (6), pp. 558-569. Date of Electronic Publication: 2023 Nov 03.
DOI:	10.14740/wjon1737
Abstrakt:	Background: Evidence from numerous observational studies and clinical trials has linked gut microbiota and metabolites to digestive tract cancer. However, the causal effect between these factors remains uncertain. Methods: Data for this study were obtained from the MiBioGen, TwinsUK Registry, and FinnGen (version R8). Two-sample Mendelian randomization analysis with inverse variance weighting method was primarily used, and the results were validated by heterogeneity analysis, pleiotropy test, and sensitivity analysis. Results: At P < 5 × 10 -8 , our analysis identified four gut microbiotas as risk factors for digestive tract cancer and six as risk factors for colorectal cancer. Conversely, one gut microbiota exhibited protection against bile duct cancer, and two showed protective effects against stomach cancer. At P < 1 × 10 -5 , our investigation revealed five, six, three, eight, eight, and eight gut microbiotas as risk factors for esophageal, stomach, bile duct, liver, pancreatic, and colorectal cancers, respectively. In contrast, four, two, eight, two, two, and five gut microbiotas exhibited protective effects against these cancers. Additionally, GABA , a metabolite of gut microbiota, displayed a significant protective effect against colorectal cancer. Conclusion: In conclusion, specific gut microbiota and metabolites play roles as risk factors or protective factors for digestive tract cancer, and a causal relationship between them has been established, offering novel insights into gut microbiota-mediated cancer development. Competing Interests: The authors declare that they have no competing interests. (Copyright 2023, Li et al.)
Databáze:	MEDLINE
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