Mutations in the gene tp53 are often detected in the early stages of colitis-associated colorectal cancer (CAC). The development of CAC is facilitated by gut microbiota disruption (dysbiosis) and chronic intestinal inflammation, but whether tp53 mutations are linked to this dysbiosis and inflammation remains unclear. To learn more, a recent study examined zebrafish larvae with a tp53 mutation. The mutant fish exhibited intestinal inflammation that was due to gut microbiota disruption. confirming the link between tp53 and these pathological changes. Overall, gut microbiome diversity was decreased, while pathogenic Aeromonas bacteria were abnormally abundant, aggressively colonizing the gut. Further investigation revealed that the gut dysbiosis in the mutants induced inflammation by disrupting sialic acid metabolism. Supporting this finding, inhibition of the sialic acid-releasing enzyme sialidase alleviated the pathologies in mutant zebrafish larvae. Although studies in rodent models and humans are needed, the results reveal that tp53 plays a crucial role in microbiome and immune balance by regulating sialic acid metabolism and suggest that manipulating the sialic acid pathway could help treat tp53 mutation-induced dysbiosis, inflammation, and related cancers like CAC.