Investigating Casual Associations Among Physical Activity, Gut Microbiota and Cancers: A Mendelian Randomization Study

Abstract Growing epidemiological evidence has shown that physical activity and gut microbiota were associated with cancer. However, causal inferences have not been confirmed. In this study, we aimed to systematically evaluate the causal relationship among physical activity, gut microbiota and cancer using a Mendelian randomization study. The genome-wide association study summary statistics data of physical activity-related phenotypes were derived from the Medical Research Council-Integrative Epidemiology Unit (MRC-IEU), the data of gut microbiota (n = 8,956) was derived from a genome-wide association analysis of 8,956 German individuals, the data of validate microbial community (n = 5,959) was derived from the Finnish Biobank located in Northern Europe, and the data of cancer-related phenotypes were derived from the Medical Research Council-Integrative Epidemiology Unit (MRC-IEU), MRBase, BCAC, INHANCE, Neale Lab, OCAC, GliomaScan, PRACTICAL. This study found that the Accelerometer − based physical activity measurement (average acceleration) (APAM) has a negative causal effect on many cancers, for example, prostate cancer, Breast cancer, Intraductal carcinoma in situ (OR = 0.999, 95% CI: 0.998–1, P BH = 0.0009), Cancer of primary lymphoid hematopoietic (OR = 0.999, 95%CI: 0.998–0.999, P BH = 0.0024). Additionally, we found evidence of a possible causal effect for physical activity on microbiota, microbiota on cancer. Mediation analyses for the effect of physical activity on microbiota shown significant effects for cancer, and microbial traits may partially mediate the effect of physical activity on cancer. Our study revealed that the physical activity was causally associated with cancer, and microbial traits may partially mediate the effect of physical activity on cancer. These results may be useful in providing clues for further mechanistic of physical activity to cancer and provide new perspectives for both healthy individuals and cancer patients in terms of prevention and improvement of various diseases.