Colon cancer and gut microbiota. comica

Background: We previously reported a gut microbiota metabolic dysbiosis and bacterial markers associated with colorectal cancer (CRC). However, it remains unclear whether these changes in the gut microbial community can be cause or consequence in CRC development. Patients and methods: In this study, human fresh stools were collected from patients with CRC (HK) and healthy individuals (HN) and were inoculated orally into germ-free mice treated with or without Azoxymethane (AOM). Gut microbiota composition was estimated by 16S rRNA genes targeted pyrosequencing. Affected pathways in the intestinal mucosa were characterized by quantifying aberrant crypt foci (ACF), Ki-67 immunostained cells as well as host gene mRNA levels associated to cell renewal and inflammation. Results: Structural difference between HK and HN donors’ microbiota at baseline remained detectable up to 42 days after stool transfers. Consequently, ACFs, numbers of Ki-67 immunostained cells, and levels of Math, Klf4, Elf3 and Hes1 mRNA in the colonic mucosa, were higher in HK than in HN recipients with highest levels observed in HK+AOM. Those genes expression differences were significantly associated with an increase of Bacteroides and a decrease Coprococcus in gut microbiota. Conclusion: Our study suggested that CRC patient microbiota is able to induce precancerous changes in the colonic mucosa of germ-free mice through alteration of host gene expression, cell proliferation and metabolism.