Association between Gut Microbiota and Digestive System Cancers: A Bidirectional Two-Sample Mendelian Randomization Study

Abstract

Accumulating evidence indicates that gut microbiota closely correlates with the tumorigenesis of digestive system cancers (DSCs). However, whether the causality between gut microbiota and DSCs exists is unknown. Genome-wide association study (GWAS) summary statistics for gut microbiota and DSCs and the bidirectional two-sample Mendelian randomization (MR) analysis were utilized to assess the causality between gut microbiota and DSCs. Sensitivity analyses were performed to evaluate the robustness of our results. We found that the genus Eggerthella (OR = 0.464, 95%CI: 0.27 to 0.796, p = 0.005) was negatively associated with the risk of gastric cancer. The genetically predicted genus Lachnospiraceae FCS020 group (OR = 0.607, 95%CI: 0.439 to 0.84, p = 0.003) correlated with a lower risk of colorectal cancer, and genus Turicibacter (OR = 0.271, 95%CI: 0.109 to 0.676, p = 0.005) was a protective factor for liver cancer. In the reverse MR, DSCs regulated the relative abundance of specific strains of gut microbiota. We comprehensively screened the association between gut microbiota and DSCs using a bidirectional two-sample MR analysis and identified the causality between several microbial taxa and DSCs. Our discoveries are beneficial for the development of novel microbial markers and microbiota-modifying therapeutics for DSC patients.

Causal effect of gut microbiota on pancreatic cancer: A Mendelian randomization and colocalization study

“…Our study employed the MR methods to investigate a causal relationship between GM and PC, aligning with the results of previous studies. [12][13][14][15][16] They revealed various associations between different types of GM and PC due to the differences in the data sources used.…”

“…Moreover, these genetic variants can potentially regulate DNA methylation (DNAm), gene expression, protein levels and the abundance of GM 10,11 . Currently, MR methods have been increasingly applied to investigate the causal relationship between GM and PC 12–16 . However, the genes potentially involved in interactions between GM and PC remain poorly understood.…”

Association between the gut microbiota, inflammatory factors, and colorectal cancer: evidence from Mendelian randomization analysis

“…The relationship between the gut microbiota and digestive may be utilized to evaluate the impact of specific microbial communities or microbial combinations on the development and treatment of cancer. Numerous similar studies have demonstrated the significant role of MR in research on the gut microbiota and digestive tract cancer ( Ni et al, 2022 ; Li et al, 2023 ; Long et al, 2023 ; Xie et al, 2023 ).…”

Causal relationships between gut microbiota and lymphoma: a bidirectional Mendelian randomization study

“…To explore potential causal associations, we adopted a locus-wide significance threshold at p = 1 × 10 -5 , consistent with thresholds frequently used in previous analyses ( Liu et al., 2022 ; Lopera-Maya et al., 2022 ). Additionally, in reverse MR analysis, we employed a lenient genome-wide significance threshold at p = 5 × 10 -6 to identify SNPs correlated with lymphoma ( Su et al., 2023 ; Xie et al., 2023 ). Second, to mitigate potential biases due to strong linkage disequilibrium (LD), we conducted an LD analysis with a threshold set at r² < 0.001 and a clumping distance of 10,000 kb, employing the 1000 Genomes Project European samples as a reference panel ( Purcell et al., 2007 ).…”