Gut Microbiota Mediate Periampullary Cancer Through Extracellular Matrix Proteins: A Causal Relationship Study

Recent studies have reported that gut microbiota may play a role in the occurrence and development of digestive system cancers. Periampullary cancer is a relatively rare digestive system cancer which lacks effective targeted therapy and specific drugs. The purpose of this study is to elucidate the relationship between periampullary cancer and gut microbiota. This work collected public genome-wide association study (GWAS) data from 211 gut microbial taxa and three types of cancer related to periampullary cancer, which were used for two-sample Mendelian randomisation (MR) analysis. Based on the analysis of differentially expressed genes between periampullary cancer and adjacent normal tissue, extracellular matrix proteins were selected for further multivariable MR analysis. Finally, the Connectivity Map was used to screen potential therapeutic drugs for periampullary cancer. Two-sample MR results confirmed that nine microbial taxa, Tyzzerella, Alloprevotella, Holdemania, LachnospiraceaeUCG010, Terrisporobacter, Alistipes, Rikenellaceae, Anaerofilum and Dialister, were associated with periampullary cancer risk. Multivariable MR discovered extracellular matrix-related proteins [Collagen alpha-1(I) chain, Laminin, Fibronectin and Mucin] that may play a role in the association between gut microbiota and periampullary cancer. Finally, the Connectivity Map identified 27 potential candidate drugs. This study can provide theoretical basis for future prevention and diagnostic research on this rare cancer.