The effects of pks+ Escherichia coli and bile acid in colorectal tumorigenesis among people with cholelithiasis or cholecystectomy

Patients with cholelithiasis (CL) or cholecystectomy (CE) would have more chances to get colorectal adenoma (CRA) or cancer (CRC). To figure out the effect of gut microbiota and bile acid on colorectal neoplasm in CL and CE patients, we executed a retrospective observational study recruited 463 volunteers, including 182 people with normal gallbladder (Normal), 135 CL and 146 CE patients. The discovery cohort was established to explore the difference of gut microbiota through 16S rRNA sequencing. The validation cohort aimed to verify the results of sequencing through qPCR. Through this research, significant enrichment of Escherichia coli was found in patients with cholelithiasis or cholecystectomy both in discovery cohort (PNormal-CL=0.013; PNormal-CE=0.042) and in validation cohort (PNormal-CL<0.0001; PNormal-CE<0.0001). The relative abundance of Escherichia coli was also increased in CRA and CRC patients (in discovery cohort, PHC-CRA=0.045, PHC-CRC=0.0016; in validation cohort, PHC-CRA=0.0063, PHC-CRC=0.0007). Pks+Escherichia coli was found enriched in CL and CE patients in validation cohort (PNormal-CL<0.0001; PNormal-CE<0.0001). Through KEGG analysis in discovery cohort, the differences of bile acid metabolism were revealed (Ko00120 primary bile acid biosynthesis P=0.014; Ko00121 secondary bile acid biosynthesis P=0.010). In validation cohort, we also found the elevation of serum total bile acid of CE patients (P<0.0001). And the level of serum total bile acid was found associated with the relative abundance of pks+ Escherichia coli (r=0.1895, P=0.0012). In one word, our research found that Escherichia coli, especially pks+ species, was enriched in CL and CE patients. Pks+ Escherichia coli and bile acid metabolism were associated with CRA and CRC in people after cholecystectomy.