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  • IDDF2024-ABS-0031 Sex hormones and blood metabolites mediating the causal associations between gut microbiota and prostate cancer: evidence from mendelian randomization study

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Basic Gastroenterology
IDDF2024-ABS-0031 Sex hormones and blood metabolites mediating the causal associations between gut microbiota and prostate cancer: evidence from mendelian randomization study
  1. Tianrui Liu1,
  2. Feixiang Yang1,
  3. Zhige Wang2,
  4. Yunyun Mei3,
  5. Hao Li1,
  6. Kun Wang4,
  7. Xiangyu Zhang2,
  8. Yiding Chen1,
  9. Yang Zhang5,
  10. Jialin Meng1,
  11. Chaozhao Liang1
  1. 1Department of Urology, The First Affiliated Hospital of Anhui Medical University; Institute of Urology, Anhui Medical University, Anhui Province Key Laboratory of Urological and Andrological Diseases Research and Medical Transformation, Anhui Medical University, China
  2. 2First School of Clinical Medicine, Anhui Medical University, China
  3. 3Fudan University Shanghai Cancer Center (Xiamen), China
  4. 4Second School of Clinical Medicine, Anhui Medical University, China
  5. 5Department of Anesthesiology and Perioperative Medicine, The Second Affiliated Hospital of Anhui Medical University, China

Abstract

Background The gut microbiota has been recognized as tumor biomarkers for various cancers, and specific tumor markers can be discovered through causal relationships. The causal relationships between gut microbiota and prostate cancer remained uncertain. We intend to identify the causal connections between gut microbiota and prostate cancer and investigate the potential underlying mechanisms.

Methods A two-sample Mendelian randomization (MR) analysis was conducted to elucidate the impact of 196 gut microbiota on prostate cancer (IDDF2024-ABS-0031 Figure 1). The reverse MR, linkage disequilibrium regression score (LDSC), and colocalization analyses were performed to strengthen causal evidence. A phenome-wide MR (Phe-MR) analysis evaluated potential side effects targeting the detected gut microbiota. We designed a two-step MR study to assess the mediation effects of circulating cytokines, sex hormones, and blood metabolites.

Results In the MR analyses, 11 bacterial taxa were causally associated with prostate cancer (IDDF2024-ABS-0031 Figure 2 (a,b)). In these bacterial taxa, Alphaproteobacteria (OR = 0.87 95% CI, 0.76-0.96, P = 0.004) restrained prostate cancer and Paraprevotella (OR = 1.08 95% CI, 1.00-1.17, P = 0.044) had a risk effect on prostate cancer. In reverse MR analysis, gut microbiota abundance was unaffected by prostate cancer. LDSC and colocalization analyses indicated that the detected associations would not be confounded by genetic correlation or LD from common causal loci (IDDF2024-ABS-0031 Figure 2 (c)). The Phe-MR analysis showed no apparent tox or side effects on the identified gut microbiota. In the mediation analysis, we found 7 mediators linking gut microbiota to prostate cancer, with a specific emphasis on the critical roles played by sex hormones and blood metabolites (IDDF2024-ABS-0031 Figure 3).

Abstract IDDF2024-ABS-0031 Figure 1
Abstract IDDF2024-ABS-0031 Figure 1
Abstract IDDF2024-ABS-0031 Figure 2
Abstract IDDF2024-ABS-0031 Figure 2
Abstract IDDF2024-ABS-0031 Figure 3
Abstract IDDF2024-ABS-0031 Figure 3

Conclusions Our study represented the first comprehensive exploration of the gut microbiota’s causal effects on prostate cancer and revealed the mediating effects of sex hormones and blood metabolites in the ‘gut-prostate axis.’ Our study has contributed to the discovery of tumor biomarkers in the gut microbiota for prostate cancer, providing a basis for early screening and treatment of the disease.

https://doi.org/10.1136/gutjnl-2024-IDDF.47

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