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

作者：Kaicen Wang, Wenrui Wu, Qing Wang, Liya Yang, Xiaoyuan Bian, Xianwan Jiang, Longxian Lv, Ren Yan, Jiafeng Xia, Shengyi Han, Lanjuan Li · 发表于：Frontiers in Microbiology · 年份：2022 · DOI：10.3389/fmicb.2022.932047 · 被引用次数：90 · 研究领域：Gut microbiota and health、Barrier Structure and Function Studies、Clostridium difficile and Clostridium perfringens research

The bidirectional relationship between colorectal cancer (CRC) and the gut microbiome has been well-documented. Here, we investigated the impact of Akkermansia muciniphila -mediated post-antibiotic gut microbial reconstitution on the development of colitis-associated CRC (CAC). The results showed that post-antibiotic replenishment of A. muciniphila worsened the tumorigenesis of CAC as indicated by increased number of large (>2 mm in diameter) tumors and both average and total tumor diameters. Measures of intestinal barrier function showed that post-antibiotic A. muciniphila gavage damaged the intestinal barrier as reflected by lower transcriptional levels of Tjp1, Ocln, Cdh1 , and MUC2 . Impaired gut barrier was followed by lipopolysaccharides (LPS) translocation as indicated by higher level of serum LPS-binding protein (LBP). The increased colonic mRNA levels of Il1b, Il6 , and Tnfa and serum levels of IL-1β, IL-6, and TNF-α indicated that post-antibiotic A. muciniphila replenishment resulted in overactivated inflammatory environment in CAC. The analysis of the evolution of the microbial community during the progression of CAC showed that post-antibiotic supplementation of A. muciniphila led to a distinct microbial configuration when compared with other treatments characterized by enriched Firmicutes, Lachnospiraceae, and Ruminococcaceae, and depleted Bacteroidetes, which was accompanied by higher Firmicutes/Bacteroidetes (F/B) ratio. Furthermore, post-antibiotic A. m...