Background: The safety of anthraquinone laxatives has been controversial. Previously, a few scattered studies have revealed that anthraquinones can cause the damage to the structure of colonic epithelial tissue, and long-term intake of anthraquinone laxatives increase the colorectal cancer risks. In this study, we focused on sennoside A, a primary purgative component in anthraquinone laxatives, and investigated the effects of sennoside A on intestinal inflammation, host metabolism, and whether it can exacerbate the colitis-associated colon cancer in the AOM/DSS mouse model. Results: Initially, sennoside A disrupted the mucus layer and mechanical barrier of the colon. The dynamic effects of sennoside A on the community structure of gut microbiota were futher anlyazed. We found sennoside A significantly promoted the dominant growth of Akkermansia muciniphila after continuous treatment for 56 days, which was independent of the prototype of sennoside A and its metabolites, including the main host metabolite rhein and bacteria metabolites. Interestingly, sennoside A suppressed the growth of butyrate-producing bacteria, thereby decreasing the butyrate levels. Besides, sennoside A directly inhibited the growth of Clostridium tyrobutyrate and Clostridium butyricum, which was not caused by the prototype of sennoside A , but the direct bacteriostatic effect produced from its metaboliterhein. Lastly, supplement with butyrate prevented sennoside A-induced gut dysbiosis and mucus barrier impairment. Conclusions: our work reveals that sennoside A can impair the integrity of the intestinal mucosal barrier, which is closely related to the disruption of the structural balance between mucus-degrading bacteria and exogenous fibro-degrading bacteria, inducing long term low-grade inflammation, metabolic disorders associated with tumorigenesis, and consequently promoting the progression of colonic carcinogenesis in the AOM/DSS mouse model.