# Genetically predicted inflammatory proteins mediate the association between gut microbiota and renal cell carcinoma

## TL;DR

This study explores how gut microbiota may influence kidney cancer through inflammatory proteins, using genetic data to uncover causal relationships.

## Contribution

The study identifies causal relationships and mediation effects using Mendelian randomization and genome-wide data.

## Key findings

- 12 positive and 15 negative causal relationships were found between gut microbiota and kidney cancer.
- Inflammatory proteins mediated the effect of gut microbiota on kidney cancer in two pathways.
- Three positive and one negative causal relationship were observed between inflammatory proteins and kidney cancer.

## Abstract

Studies have indicated a potential relationship between gut microbiota and renal cell carcinoma. However, the causal relationship between various types of gut microbiota and renal cell carcinoma, as well as the role of inflammatory protein as mediators, remains unclear.

This study aimed to identify the relationship between gut microbiota, inflammatory protein, and renal cell cancer through a large-scale genome-wide association study (GWAS) utilizing pooled data. We employed Mendelian randomization (MR) to investigate the causal relationship among these variables. Inverse variance weighting (IVW) was utilized as the primary statistical method. Furthermore, we examined the mediating role of inflammatory protein in the pathway through which gut microbiota influences the development of renal cell cancer.

The analysis revealed 12 positive causal relationships and 15 negative causal relationships between the genetic liability of gut microbiota and renal cell cancer. Furthermore, there were three positive causal relationships and one negative causal relationship between inflammatory proteins and renal cell cancer. There were two axes of relationships in which gut microbiota promote the development of renal cell cancer. through inflammatory proteins acting as mediators.

Gut microbiota and inflammatory protein were causally related to renal cell cancer, and inflammatory protein were intermediary factors in the pathway between gut microbiota and renal cell cancer.

The online version contains supplementary material available at 10.1007/s12672-025-01980-y.