BACKGROUND: Dysbiosis, characterized by imbalanced gut microbiota, is common in patients with inflammatory bowel disease (IBD) and colitis-associated colorectal cancer (CAC). While probiotics theoretically offer promise for IBD treatment, their actual efficacy remains uncertain, leading to non-recommendation in current guidelines. Akkermansia muciniphila (AKK) is a potential next-generation probiotic strain with benefits in obesity, diabetes and gut protection. Recent study showed reduced AKK abundance in IBD patients and mice with colitis and CAC. Hence, we administered AKK treatment to these mice to assess its effects. METHODS: Using a mouse model of colitis and CAC induced by azoxymethane/dextran sodium sulfate (AOM/DSS) in BALB/c mice, we administered AKK orally to mice on the AOM/DSS protocol with 5 x 10(8) CFU of AKK three times a week for a total 27 times. The treatment effect of AKK were evaluated. RESULTS: Despite AKK supplementation, mice showed no significant differences in body weight, colon length, histological inflammation, or short chain fatty acid composition compared to those on the AOM/DSS protocol alone. Unexpectedly, AKK-treated mice exhibited decreased AKK abundance in stool samples, suggesting poor adherence and colonization despite supplementation. These results parallel our previous findings with Clotridium butyricum, indicating challenges in probiotic intervention for severe colitis and CAC due to mucosal barrier damage. CONCLUSION: Our study highlights the limitations of probiotic therapy in IBD, attributing its failure to inadequate adherence and colonization in damaged mucosal barriers. Further research is warranted to clarify the role of probiotics in IBD management.