Numerous data show that taraxacum officinale extract (TOE) exerts protective effects on inflammatory diseases. However, the underlying mechanisms by which TOE affects dextran sulphate sodium (DSS)âinduced colitis remain unclear. After DSSâinduced colitis were treated with different concentrations of TOE for 8 days, the bodyweight, disease activity index (DAI), colon lengths and pathological scoring were assessed, and histopathological examination was confirmed by HE staining. Furthermore, a transcriptome sequencing was performed by using the colon tissues between TOE and DSS groups, and the differentially expressed genes were conducted for the Kyoto Encyclopaedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA) and were validated by qRTâPCR and immunohistochemistry analysis. In addition, a 16S rDNA sequencing was carried out to distinguish the differential gut microbiota by using the mouse faecal samples between TOE and DSS groups. We found that TOE attenuated the clinical symptoms, lowered the inflammatory scoring and inhibited the secretion of proinflammatory factors TNFâα, ILâ1ÎČ and ILâ6 in DSSâinduced colitis. KEGG and GSEA analysis demonstrated that fatty acid degradation and cytokineâreceptor signalling were predominantly enriched in TOEâtreated colitis as compared with the DSS group. Further investigations revealed that TOE increased the expression levels of Adh5, Aldh3a2 and Acox3, but decreased those of CCL20, CCR6 and CXCL1/5 in DSSâinduced colitis, where TOE also induced the enrichment of S24â7 and adlercreutzia, but decreased the amount of anaerostipes, enterococcus, enterobacteriaceae and peptostreptococcaceae. In conclusion, TOE ameliorated DSSâinduced colitis by regulating fatty acid degradation and microbial dysbiosis.