The negative effect of Akkermansia muciniphila-mediated post-antibiotic reconstitution of the gut microbiome on the development of colitis-associated colorectal cancer in mice

Numerous studies demonstrated the close relationship between colorectal cancer (CRC) and the gut microbiome. Destruction of the gut microbiome is the common side effect of antibiotic. Naturally, after antibiotic stopped, the destroyed microbial community would experience a reconstruction. Probiotics have been widely applied to treat the antibiotics-caused dysbiosis. Akkermansia muciniphila was proposed as a next generation probiotic and its abundance was decreased in CRC. Here, our work investigated the influence of spontaneous as well as A. muciniphila-involved post-antibiotic microbial reconstitution on the development of colitis-associated CRC (CAC). The result showed that voluntarily microbial reconstruction after the early short period of antibiotic treatment exhibited no impact on the long progress of inflammation-associated tumorigenesis. Nevertheless, replenishment of A. muciniphila after antibiotic pretreatment even worsen the tumorigenesis of CAC as indicated by increased big tumor (>2mm in diameter) number and both average and total tumor diameter. We further analyzed dynamic changes of microbial community during the progress of CAC and found that post-antibiotic supplementation of A. muciniphila shaped a distinct microbial composition when compared with other groups. Bacteria replenishment enriched Firmicutes, unidentified_Rumonicocaccaceae, and Odoribacter, while depleted Bacteroidetes, Bacteroides, and Paraprevotella. Meanwhile, A. muciniphila administration changed the bile acid metabolic profile as reflected by decreasing the concentration of some secondary bile acids, like wMCA, DCA, muroCA, HDCA, 6-Keto-LCA, and the concentration of wMCA might associated with the severity of tumorigenesis. In addition, A. muciniphila also impacted the metabolism of short chain fatty acids (SCFAs) as the concentrations of acetic acid, propionic acid, butyric acid, and valeric acid were increasing in group treated with A. muciniphila.