Causal effect of gut microbiota on the risk of cancer and potential mediation by inflammatory proteins

Background
While growing evidence highlights the role of gut microbiota and inflammatory proteins in cancer, with cancer-related inflammation now considered the seventh hallmark of cancer, the direct causal relationships between specific microbiota, cancer, and the potential mediating effects of inflammatory proteins have not been fully established.

Methods
We employed Mendelian randomization (MR) to assess the causal relationships between gut microbiota, inflammatory proteins, and eighteen distinct cancers using data from extensive genome-wide association studies (GWAS). The primary statistical method utilized was inverse variance weighting (IVW). We also investigated whether inflammatory proteins could mediate the effects of gut microbiota on cancer development.

Results
Our findings revealed 42 positive and 49 inverse causal impacts of gut microbiota on cancer risk (P < 0.05). Additionally, we identified 32 positive and 28 inverse causal relationships between inflammatory proteins and cancer risk. Moreover, genus Collinsella decreased the risk of lung cancer by decreasing levels of T-cell surface glycoprotein CD5 (mediating effect = 16.667%), while genus Ruminococcaceae UCG005 increased the risk of mesothelioma by increasing levels of CCL4 (mediating effect = 5.134%).ConclusionsOur study provides evidence for a causal association between gut microbiota, inflammatory proteins, and eighteen different cancer types. Notably, the T-cell surface glycoprotein CD5 and CCL4 were identified as mediators linking the genus Collinsella with lung cancer and the genus Ruminococcaceae UCG005 with mesothelioma, respectively.